Serum Carbohydrate Antigen 19-9 and Metabolite Hypotaurine Are Predictive Markers for Early Recurrence of Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC. MATERIALS AND METHODS: Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group. RESULTS: Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence ( P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%. CONCLUSIONS: Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.

Internal hernia after laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein: A case report.

Several studies have recently reported the rare occurrence of internal herniation of the small bowel after laparoscopic colorectal surgery. Most cases of internal herniation after laparoscopic colorectal surgery occur due to a mesenteric defect. However, there have been no reports on the indications for closing mesenteric defects to prevent the development of an internal hernia. This study reports a case of an internal hernia of the proximal jejunum near the ligament of Treitz in a patient who underwent laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein. Assessing the risk for internal herniation before completing the initial surgery is crucial. Additionally, mesenteric defect closure should be performed to prevent the development of internal hernias among patients with a potential risk.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Constrictive pericarditis caused by pericardial metastasis from esophageal squamous cell carcinoma: a case report.

Constrictive pericarditis is a rare condition characterized by clinical signs of right heart failure subsequent to the loss of pericardial compliance. We report a case of constrictive pericarditis due to pericardial metastasis in a patient with a history of esophageal squamous cell carcinoma that had a pathological complete response (pCR) to preoperative chemoradiotherapy. A 66-year-old woman was referred to our division for the treatment of advanced esophageal cancer. Video-assisted thoracoscopic surgery esophagectomy (VATSE) with 3-field lymphadenectomy was performed after neoadjuvant chemoradiotherapy (NAC-CRT). Pathological examination revealed no residual tumor, lymph node metastasis, lymphatic invasion, or vessel invasion. The histological treatment effect of the chemoradiotherapy was pathological complete response (pCR). Five months after surgery, the patient was admitted to a nearby hospital for the treatment of acute pericarditis. However, a month after admission, acute pericarditis progressed to constrictive pericarditis, and she was referred to our hospital for further management. Subsequently, urgent pericardiectomy was performed through a lower half sternotomy incision. After surgery, heart failure improved for a while but worsened again. The patient died 7 days after the surgery. Pathological examination of the resected pericardium revealed evidence of metastasis from squamous cell carcinoma of the esophagus. An autopsy revealed the spread of esophageal cancer to the bilateral pleura, right lung, pericardium, diaphragm, soft tissue surrounding the tracheal bifurcation, and bilateral hilar lymph nodes. Similarly, tumor cells were found in the lymphatic vessels of the pericardium and pleura. Even if pCR is achieved with NAC-CRT, as in our case, esophageal cancer may metastasize and present as constrictive pericarditis within a short period; therefore, careful patient follow-up is essential.

Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.

OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.

Early gastric cancer with an Adachi type VI (group 26) vascular anomaly diagnosed preoperatively and treated by laparoscopic surgery: a case report.

BACKGROUND: It is important to understand the branching pattern of the celiac artery for a safe surgery. Various branching anomalies of the celiac artery were classified by Adachi in 1928. In Adachi's classification, type VI (group 26) is a rare anatomical anomaly (0.4%) that requires care when carrying out a surgery in gastric cancer patients with this anomaly. Herein, we reported a case treated successfully with laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer. CASE PRESENTATION: An 84-year-old female was referred to our division for an additional surgical treatment for early gastric cancer that was resected by endoscopic submucosal dissection. A three-dimensional computed tomography angiography revealed an angioplany of the common hepatic artery branching from the left gastric artery. According to Adachi's classification, the anomaly of this patient corresponded to type VI (group 26). Preoperative anatomical information of this rare anomaly helped us to safely perform a laparoscopic distal gastrectomy and lymph node dissection with common hepatic artery preservation. The patient had an uneventful postoperative course and was discharged on postoperative day 11. CONCLUSIONS: We consider that Group 26 anomalies require the most precise anatomical understanding among Adachi classification type VIs, since it affects hepatic blood flow and can cause serious complications. In this time, we reported a successful case to perform laparoscopic distal gastrectomy with safety and accuracy by preoperative understanding of the precise vascular anatomy.

Laparoscopic hand-sewn esophagojejunal anastomosis in laparoscopic proximal gastrectomy for early gastric cancer.

PURPOSE: In Asian countries, proximal gastrectomy is a standard treatment option for early primary gastric cancer located in the upper third of the stomach. However, laparoscopic proximal gastrectomy (LPG) is not widely employed due to the technical difficulty of laparoscopic esophagojejunal anastomosis. Therefore, we began performing laparoscopic hand-sewn esophagojejunal anastomosis. In this report, we describe the technique of this method and the short-term surgical outcomes. METHODS: Between February 2016 and June 2020, 18 patients underwent LPG with double-tract reconstruction at our institution. Laparoscopic hand-sewn esophagojejunal anastomosis was attempted for all patients. RESULTS: The median operative time for the 18 patients was 431 min (range: 301-549 min), and the estimated blood loss was 100 mL (range: 0-1524 mL). The median time for the hand-sewn esophagojejunostomy was 42 min (range: 26-81 min). Only one case was converted to open surgery after the reconstruction due to bleeding from an artery of the lesser curvature. No anastomotic leakage was observed in any patients (0/18, 0 %); however, two patients developed anastomotic stenosis (2/18, 11%). The mean length of postoperative hospital stay was 10 days (range: 8-28 days). CONCLUSION: The laparoscopic hand-sewn esophagojejunal anastomosis in LPG is a simple, cost-effective, and safe procedure. We believe that our method is a feasible choice. However, careful and longer follow-up of more patients is necessary to determine the advantages of our method.

Four cases of laparoscopic colectomy for sigmoid colon and rectal cancer with persistent descending mesocolon.

BACKGROUND: Persistent descending mesocolon (PDM) is a congenital anomaly associated with the failure of fixation of the descending colon to the lateral abdominal wall. In the laparoscopic colectomy for colorectal cancer, it has been noticed that there are extensive adhesions and a distinctive anatomy of colonic vessels in cases with PDM. Therefore, it is necessary to have sufficient knowledge about PDM so that it can be appropriately treated during surgery. CASE PRESENTATION: Case 1-a 79-year-old man underwent laparoscopic intersphincteric resection for rectal cancer. Preoperative barium enema (BE) revealed that the sigmoid colon was located at the right side of the abdomen. An enhanced computed tomography (CT) showed that the common trunk of the left colic artery (LCA) and the first sigmoid colonic artery (S1) branched from the inferior mesenteric artery (IMA). Case 2-a 68-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer and laparoscopic distal gastrectomy for gastric cancer synchronously. BE showed that the descending colon ran from the splenic flexure to medial caudal side. An enhanced CT showed that the distance from the LCA to the marginal artery was 1.0 cm. Case 3-a 68-year-old man underwent laparoscopic low anterior resection for rectal cancer. BE showed that the descending colon ran to the medial caudal side. An enhanced CT showed that the mesentery of the descending colon was comparatively shortened. Case 4-a 60-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. An enhanced CT showed that the descending colon ran to the medial caudal side and predicted that the LCA and S1 formed a common trunk and branched radially from the IMA. We reported four cases with PDM recognized preoperatively as above. Three cases had a shortening of the mesocolon. While dissecting the vessels, although special attention was required to maintain the blood flow to the intestine, none of these cases developed any complications during the postoperative course. CONCLUSIONS: We considered that it is important to have positional awareness of the LCA and the marginal artery to perform the laparoscopic surgery safely when a colorectal cancer with PDM is diagnosed preoperatively using imaging methods.

Spontaneous regression of advanced transverse colon cancer with remaining lymph node metastasis.

BACKGROUND: The observation of spontaneous regression (SR) has been well documented for many cancer types, including renal cell carcinoma, non-Hodgkin's lymphoma, leukemia, neuroblastoma, and malignant melanoma. However, the SR frequency in colorectal cancer is very rare. Therefore, the accumulation of SR colorectal cancer cases might contribute to find the regression mechanism. CASE PRESENTATION: A 67-year-old woman received colonoscopy due to being positive for fecal occult blood testing and was diagnosed as having a transverse colon cancer at a local hospital. She was admitted to our institution for surgical treatment of the colon cancer. The colonoscopy revealed a type 2 tumor of 13 mm in diameter at the hepatic flexure of the transverse colon. The enhanced computed tomography (CT) showed an enlarged lymph node in the intermediate lymph node region. The 18F-fluorodeoxyglucose positron emission tomography/CT showed no abnormal accumulation on the transverse colon; however, an abnormal accumulation was found at the enlarged lymph node. The patient was preoperatively diagnosed as having advanced transverse colon cancer with lymph node metastasis and underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Pathological examination showed only a scar-like tissue and no cancerous lesion in the transverse colon, while a metastatic lymph node was histologically confirmed in the intermediate lymph node region. Loss of MLH1 and PMS2 expression was observed in the cancer cells of both biopsy specimens and resected lymph nodes. No recurrence was seen for 5 years after surgery. CONCLUSIONS: We reported a rare case of SR of the primary transverse colon cancer without regression of the metastatic regional lymph node. We considered that colorectal cancer with SR should be resected because even if SR of the primary lesion occurs, lymph node metastasis might have an inconsistent behavior as shown in the present case.

New Concept Air Conditioning System for the Operating Room to Minimize Patient Cooling and Surgeon Heating: A Historical Control Cohort Study.

BACKGROUND: Intraoperative hypothermia is a common adverse event. For avoiding the complication due to hypothermia, many warming devices and methods have been used in perioperative period. It has been reported that more patients undergoing laparoscopic surgery tend to have hypothermia than with open surgery. To avoid intraoperative hypothermia, many kinds of warming tools have been used. But, it was also reported that some warming methods increased perceptions of distraction and physical demand. METHODS: To achieve both patients' normothermia and surgeons' comfort, new air conditioning (AC) system was designed with considering the characteristics of laparoscopic surgery. The temperature of the airflows to the patient and to the surgeons can be adjusted independently in this new system. The new system has two parts. One controls the temperature of the central area over the operation table. The air from this part falls on the patients. The other part is the lateral area beside the operating table; the air from this part falls on the surgeons. The subjects of this study were 160 gastric cancer patients and 316 colorectal cancer patients undergoing laparoscopic surgery. The temperature of the central flow was set 23.5 °C, and the temperature of the lateral flow was set 22 °C just after the anesthesia. The number of timepoints the patient spent in hypothermic state, defined as a temperature cooler by 0.5 °C or more than that at the starting point of surgery, was determined in each patient. RESULTS: In the results, the rate of hypothermic state in old operation rooms was 23.8% and that in new operation rooms was 2.7% in male gastric cancer patients (p < 0.01). And those were 37.1% in old operation rooms and 0.9% in new operation rooms in female gastric cancer patients (p < 0.01). The rate of hypothermic state in old operation rooms was 30.0% and that in new operation rooms was 9.5% in male colorectal cancer patients (p < 0.01). And those were 41.6% in old operation rooms and 8.9% in new operation rooms in female colorectal cancer patients (p < 0.01). The similar results were showed in the study, which subjects were limited the patients undergoing surgery in 2015 and 2016; which were the last year the old operation rooms were used and the first year the new operation rooms were used. CONCLUSIONS: Thus, the usefulness of the new air conditioning system for achieving both patients' normothermia and comfort of surgeons could be verified in this study.

FGF5 methylation is a sensitivity marker of esophageal squamous cell carcinoma to definitive chemoradiotherapy.

Definitive chemoradiotherapy (dCRT) is the major treatment for esophageal squamous cell carcinoma (ESCC), and prediction of the response to dCRT is important so as not to miss an opportunity to cure an ESCC. Nevertheless, few validated markers are available. Here, we aimed to identify a highly reproducible marker using multi-layer omics analysis. 117 ESCC samples from 67 responders and 50 non-responders were divided into screening, validation, and re-validation sets. In the screening cohort (n = 41), somatic mutations in 114 genes showed no association with dCRT response. Genome-wide DNA methylation analysis using Infinium HumanMethylation450 BeadChip array identified four genic regions significantly associated with dCRT response. Among them, FGF5 methylation was validated to be associated with dCRT response (n = 34; P = 0.001), and further re-validated (n = 42; P = 0.020) by bisulfite-pyrosequencing. The sensitivity and specificity in the combined validation and re-validation sets (n = 76) were 45% and 90%, respectively, by using the cut-off value established in the screening set, and FGF5 methylation had predictive power independent from clinicopathological parameters. In ESCC cell lines, FGF5 promoter methylation repressed its expression. FGF5 expression was induced by cisplatin (CDDP) treatment in three unmethylated cell lines, but not in two methylated cell lines. Exogenous FGF5 overexpression in a cell line with its methylation conferred resistance to CDDP. In non-cancerous esophageal tissues, FGF5 was not expressed, and its methylation was present in a small fraction of cells. These results showed that FGF5 methylation is a validated marker for ESCC sensitivity to dCRT.

A case of Schloffer tumor with rapid growth and FDG-PET positivity at the port site of laparoscopic sigmoidectomy for colon cancer.

BACKGROUND: Schloffer tumor is a foreign body granuloma in the abdominal subcutaneous layer that develops due to a foreign body such as suture from several months to years postoperatively. Herein, we report a case of a rapidly growing Schloffer tumor with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) positivity at the port site of laparoscopic sigmoidectomy for colon cancer. CASE PRESENTATION: An 85-year-old man, who underwent laparoscopic sigmoidectomy for stage IIIa sigmoid colon cancer 10 months ago, was referred to our hospital with complaints of a growing mass in the abdominal wall. The tumor was palpable at the right-sided abdominal wall corresponding to the port site of laparoscopic sigmoidectomy. The tumor rapidly grew for 2 months. Computed tomography showed a ring-enhanced mass at the right-sided abdominal wall. PET examination revealed high accumulation of FDG in the tumor. Tumor resection was performed due to suspected port site recurrence. The pathological diagnosis was inflammatory granuloma, so-called Schloffer tumor. CONCLUSION: In the era of laparoscopic surgery, Schloffer tumor may be one of the differential diagnoses for rapidly growing tumor with FDG-PET positivity at the port site in postoperative patients with advanced colorectal cancer.

Identification of gastrointestinal perforation based on ICD-10 code in a Japanese administrative medical information database and associated drug exposure risk factors.

PURPOSE: The purpose of this study is to evaluate the accuracy of gastrointestinal (GI) perforation ICD-10 coding in the Diagnosis Procedure Combination (DPC) database and to examine drug exposure risk factors for GI perforation. METHODS: A total of 100 patients with GI perforation ICD-10 codes were selected randomly from Kagawa University Hospital's DPC database between April 2011 and December 2016. Two experienced specialist physicians independently reviewed the medical records and classified cases as "definite A," "definite B," "probable," or "no GI perforation." The positive predictive values (PPVs) of "definite A/B" cases were calculated after stratification by sex, age, ICD-10 code, and diagnostic information in the DPC data. The number of prescribed drugs with side effects of GI perforation according to historical data was compared between "definite A/B" and "no GI perforation" cases. RESULTS: The overall PPV was 47.0% (95% confidence interval [CI], 36.9-57.2). However, the PPVs for the three categories of diagnostic information in the DPC data ("main diagnosis," "diagnosis causing admission," and "most resource-intensive diagnosis") were each more than 70% after excluding inappropriate patients. Additionally, the PPV focused on these three categories was 76.3% (95% CI, 59.8-88.6). Prescribed drugs with side effects of GI perforation were more frequently detected in "definite A/B" cases (P = .028). CONCLUSIONS: Although the overall PPV for GI perforation based on ICD-10 code was low, our results suggest that the PPV could be improved by appropriate selection of DPC diagnosis category and that use of multiple medications enhances the risk of GI perforation.

A solitary fibrous tumor in the pelvic cavity of a patient with Doege-Potter syndrome: a case report.

BACKGROUND: A solitary fibrous tumor (SFT) is a mesenchymal lesion, which commonly develops in the thorax. Non-islet cell hypoglycemia is a rare paraneoplastic phenomenon caused by an extra-pancreatic tumor. We report a rare case of a pelvic SFT with severe hypoglycemia, which was considered to be Doege-Potter syndrome. CASE PRESENTATION: A 72-year-old man was referred to our hospital for treatment of hypoglycemia and a large pelvic tumor. His blood glucose level was 52 mg/dl; serum insulin level, 1.0 µIU/ml; C-peptide level, 0.2 ng/ml; and insulin-like growth factor-I (IGF-I) level, 31 ng/ml. Contrast-enhanced computed tomography (CT) showed a 13-cm mass in the pelvic cavity. Magnetic resonance imaging (MRI) revealed a lobulated tumor with iso- and high-intensity areas combined in T2-weighted images. No clear invasion to any adjacent organs was identified. The tumor was resected, and hypoglycemic symptoms disappeared immediately. Pathological diagnosis was an SFT with malignant potential that secreted IGF-II and caused hypoglycemia. There has been no tumor recurrence during the 1 year of follow-up. CONCLUSION: Non-islet cell tumor hypoglycemia should be considered in the differential diagnosis of patients presenting with tumors and hypoglycemia.

Pure laparoscopic pancreas parenchymal dissection using CUSA for distal pancreatectomy.

Although stapler dissection and closure is commonly used for laparoscopic distal pancreatectomy (LDP), it is risky in patients with thick pancreatic parenchyma or titanium allergy. We performed laparoscopic pancreatic parenchymal dissection with cavitron ultrasonic surgical aspirator (CUSA) successfully in a patient with titanium allergy. Slinging the pancreas with nylon tape delineates the surgical plane. Pancreatic parenchyma was transected by CUSA in an almost bloodless field. Pancreatic duct branches and vessels were adequately exposed and dissected with a vessel sealing system. The main pancreatic duct was closed with Hem-O-lock. CUSA is an alternative to stapler dissection during LDP in select patients.

Esophageal cancer associated with a sarcoid-like reaction and systemic sarcoidosis in lymph nodes: supportive findings of [18F]-fluorodeoxyglucose positron emission tomography-computed tomography during neoadjuvant therapy.

BACKGROUND: In patients with esophageal cancer, differentiation between lymph node metastasis and lymphadenopathies from sarcoidosis or sarcoid-like reactions of lymph nodes is clinically important. Herein, we report two esophageal cancer cases with lymph node involvement of sarcoid-like reaction or sarcoidosis. CASE PRESENTATION: One patient received chemotherapy and the other chemoradiotherapy as initial treatments. In both cases, [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) was performed before and after chemo(radio)therapy. After the treatment, FDG uptake was not detected in the primary tumor, but it was slightly reduced in the hilar and mediastinal lymph nodes in both cases. These non-identical responses to chemo(radio)therapy suggest the presence of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of the esophagus. Curative surgical resection was performed as treatment. CONCLUSIONS: These FDG-PET/CT findings may be helpful to distinguish between metastasis and sarcoidosis-associated lymphadenopathy in esophageal cancer.

Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues.

Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.