Clinicopathological Characteristics of Anastomotic Recurrence After Curative Resection for Colorectal Cancer: Comparison With Nonanastomotic Local Recurrences.

BACKGROUND: Anastomotic recurrence is thought to be caused by implantation of tumor cells to the anastomotic line; however, its risk factors and prognostic significance remain unclear. OBJECTIVE: This study aimed to clarify the risk factors for anastomotic recurrence in colorectal cancer and assess the prognosis in comparison to nonanastomotic local recurrence. DESIGN: A single-center retrospective observational study. SETTINGS: The medical records of the study participants were retrospectively collected from the Department of Surgical Oncology at the University of Tokyo Hospital database. PATIENTS: This study included 1584 patients with colorectal cancer who underwent surgical resection between January 2005 and December 2017. We focused on 15 patients who had an anastomotic recurrence. MAIN OUTCOME MEASURES: The main outcome measures were the risk factors of anastomotic recurrence at the primary resection and prognosis data in comparison to that of nonanastomotic local recurrence. RESULTS: There were 15 patients (0.95%) with anastomotic recurrence and 35 (2.21%) with nonanastomotic local recurrence. Univariate analysis revealed that lymph node metastasis and advanced T stage are the risk factors for anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that of those with nonanastomotic local recurrence who underwent resection. LIMITATIONS: The small number of patients with anastomotic recurrence is a major limitation of this study. Additionally, the retrospective study design may have increased the risk of selection bias. CONCLUSIONS: Lymph node metastasis and advanced T stage were associated with anastomotic recurrence. The prognosis of patients with anastomotic recurrence was similar to that with resected nonanastomotic local recurrence. Thus, surveillance should be carefully continued while considering the poor prognosis of patients with anastomotic recurrence. See Video Abstract at http://links.lww.com/DCR/C92 . CARACTERSTICAS CLINICOPATOLGICAS DE LA RECURRENCIA ANASTOMTICA DESPUS DE LA RESECCIN CURATIVA DEL CNCER COLORRECTAL COMPARACIN CON LAS RECURRENCIAS LOCALES NO ANASTOMTICAS: ANTECEDENTES:Se cree que la recurrencia anastomótica es causada por la implantación de células tumorales en la línea anastomótica; sin embargo, los factores de riesgo asociados y el significado en cuanto a pronóstico siguen sin estar claros.OBJETIVO:Este estudio tuvo como objetivo aclarar los factores de riesgo para la recurrencia anastomótica en el cáncer colorrectal y evaluar el pronóstico en comparación con la recurrencia local no anastomótica.DISEÑO:Un estudio observacional retrospectivo de un solo centro.ESCENARIO:Los registros médicos de los participantes del estudio se recopilaron retrospectivamente de la base de datos del Departamento de Cirugía Oncológica del Hospital de la Universidad de Tokio.PACIENTES:Este estudio incluyó a 1584 pacientes con cáncer colorrectal que se sometieron a resección quirúrgica entre enero de 2005 y diciembre de 2017. Nos enfocamos en 15 pacientes que tuvieron recurrencia anastomótica.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron los factores de riesgo de recurrencia anastomótica en la resección primaria y los datos de pronóstico en comparación con la recurrencia local no anastomótica.RESULTADOS:Hubo 15 pacientes (0.95%) con recurrencia anastomótica y 35 (2.21%) con recurrencia local no anastomótica. El análisis univariable reveló que la metástasis en los ganglios linfáticos y el estadio T avanzado son los factores de riesgo para la recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de aquellos con recidiva local no anastomótica sometidos a resección.LIMITACIONES:El pequeño número de pacientes con recurrencia anastomótica es una limitación importante de este estudio. Además, el diseño retrospectivo del estudio puede haber aumentado el riesgo de sesgo de selección.CONCLUSIONES:La metástasis en los ganglios linfáticos y el estadio T avanzado se asociaron con recurrencia anastomótica. El pronóstico de los pacientes con recidiva anastomótica fue similar al de la recidiva local no anastomótica resecada. Por lo tanto, la vigilancia debe continuarse cuidadosamente considerando el mal pronóstico de los pacientes con recurrencia anastomótica. Consulte Video Resumen en http://links.lww.com/DCR/C92 . (Traducción-Dr. Jorge Silva Velazco ).

Surgical outcomes of robotic, laparoscopic, and open low anterior resection after preoperative chemoradiotherapy for patients with advanced lower rectal cancer.

PURPOSE: We investigated the surgical outcomes of robotic low anterior resection (LAR) for lower rectal cancer after preoperative chemoradiotherapy (pCRT). METHODS: A total of 175 patients with lower rectal cancer who underwent LAR after pCRT between 2005 and 2020 were stratified into open (OS, n = 65), laparoscopic (LS, n = 64), and robotic surgery (RS, n = 46) groups. We compared the clinical, surgical, and pathological results among the three groups. RESULTS: The RS and LS groups had less blood loss than the OS group (p < 0.0001). The operating time in the RS group was longer than in the LS and OS groups (p < 0.0001). The RS group had a significantly longer mean distal margin than the LS and OS groups (25.4 mm vs. 20.7 mm and 20.3 mm, respectively; p = 0.026). There was no significant difference in the postoperative complication rate among the groups. The local recurrence rate in the RS group was comparable to those in the LS and OS groups. CONCLUSION: Robotic LAR after pCRT was performed safely for patients with advanced lower rectal cancer. It provided a longer distal margin and equivalent local control rates.

Performance of an artificial intelligence-based diagnostic support tool for early gastric cancers: Retrospective study.

OBJECTIVES: Endoscopists' abilities to diagnose early gastric cancers (EGCs) vary, especially between specialists and nonspecialists. We developed an artificial intelligence (AI)-based diagnostic support tool "Tango" to differentiate EGCs and compared its performance with that of endoscopists. METHODS: The diagnostic performances of Tango and endoscopists (34 specialists, 42 nonspecialists) were compared using still images of 150 neoplastic and 165 non-neoplastic lesions. Neoplastic lesions included EGCs and adenomas. The primary outcome was to show the noninferiority of Tango (based on sensitivity) over specialists. The secondary outcomes were the noninferiority of Tango (based on accuracy) over specialists and the superiority of Tango (based on sensitivity and accuracy) over nonspecialists. The lower limit of the 95% confidence interval (CI) of the difference between Tango and the specialists for sensitivity was calculated, with >-10% defined as noninferiority and >0% defined as superiority in the primary outcome. The comparable differences between Tango and the endoscopists for each performance were calculated, with >10% defined as superiority and >0% defined as noninferiority in the secondary outcomes. RESULTS: Tango achieved superiority over the specialists based on sensitivity (84.7% vs. 65.8%, difference 18.9%, 95% CI 12.3-25.3%) and demonstrated noninferiority based on accuracy (70.8% vs. 67.4%). Tango achieved superiority over the nonspecialists based on sensitivity (84.7% vs. 51.0%) and accuracy (70.8% vs. 58.4%). CONCLUSIONS: The AI-based diagnostic support tool for EGCs demonstrated a robust performance and may be useful to reduce misdiagnosis.

Prognoses in Pathologically Confirmed T1 Lower Rectal Cancer Patients with or without Preoperative Therapy: An Analysis Using the Surveillance, Epidemiology, and End Results Database.

INTRODUCTION: Preoperative chemoradiotherapy (CRT) is the standard therapy for downstaging in locally advanced lower rectal cancer. However, it remains unclear whether rectal cancers downstaged by preoperative therapy show similar prognoses to those of the same stage without preoperative therapy. We previously demonstrated that preoperative CRT did not affect prognosis of rectal cancer with pathological T1N0 (pT1N0) stage in a single institute. Here, using a larger dataset, we compared prognoses of (y)pT1 rectal cancer stratified by the use of preoperative therapy and analyzed prognostic factors. METHODS: Cases of pT1N0 rectal cancer, registered between 2004 and 2016, were extracted from the Surveillance, Epidemiology, and End Results database. Patients were categorized as the "ypT1 group" if they had undergone preoperative therapy before surgery or as the "pT1 group" if they had undergone surgery alone. Overall survival (OS) and cancer-specific survival (CSS) between these groups of patients were compared. Factors associated with CSS and OS were identified by univariate and multivariate analyses. RESULTS: Among 3,757 eligible patients, ypT1 and pT1 groups comprised 720 and 3,037 patients, respectively. While ypT1 patients showed poorer CSS than ypT1 patients, there was no significant difference in OS. Preoperative therapy was not an independent prognostic factor for CSS or OS. Multivariate analysis identified age and histological type as significant factors associated with CSS. Sex, age, race, and number of lymph nodes dissected were identified as significant factors associated with OS. CONCLUSIONS: Prognosis among patients with (y)p T1N0 rectal cancer was similar irrespective of whether they underwent preoperative therapy, which is consistent with our previous observations.

Clinical impact of primary tumor sidedness and sex on unresectable post-recurrence survival in resected pathological stage II-III colorectal cancers: a nationwide multicenter retrospective study.

BACKGROUND: Several studies have demonstrated that right-sided tumors have poorer prognosis than left-sided tumors in patients with unresectable colorectal cancer (CRC). The predictive ability of the tumor sidedness in CRC treated with chemotherapy in each sex is unclear. METHODS: Subjects were 964 unresectable recurrent patients treated with chemotherapy with stage II-III CRC after curative resection between 2004 and 2012. Post-recurrence cancer-specific survival (CSS) for each sex was examined. RESULTS: Patients were 603 males (222 right-side tumors (cecum to transverse colon) and 381 left-sided tumors (descending colon to rectum)), and 361 females (167 right-side tumors and 194 left-sided tumors). Right-sided tumors developed peritoneal recurrences in males and females. Left-sided tumors were associated with locoregional recurrences in males and with lung recurrences in females. Right-sided tumors were associated with shorter post-recurrence CSS in both sexes. In males, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.53, P < 0.0001) together with the presence of regional lymph node metastasis histopathological type of other than differentiated adenocarcinoma, the recurrence of liver only, the recurrence of peritoneal dissemination only, and relapse-free interval less than one-year. In females, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.50, P = 0.0019) together with advanced depth of invasion, the presence of regional lymph node metastasis, and recurrence of liver only. CONCLUSIONS: Primary tumor sidedness in both sexes in unresectable recurrent CRC patients treated with chemotherapy may have prognostic implications for post-recurrence CSS.

Poor nutrition and sarcopenia are related to systemic inflammatory response in patients with rectal cancer undergoing preoperative chemoradiotherapy.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard therapy for locally advanced rectal cancer (LARC). However, the changes that the patient's physical status during CRT, such as host systemic inflammatory response, nutritional status, and muscle depletion, are still unclear. We evaluated the clinical significance of malnutrition and sarcopenia for patients with LARC undergoing CRT. PATIENTS AND METHODS: Patients with LARC treated with CRT following radical surgery at our institution between 2006 and 2016 (N = 225) were retrospectively analyzed. A new prognostic score (PNSI) was devised based on the prognostic nutritional index (PNI) and the psoas muscle mass index (PMI): patients with malnutrition/sarcopenia were scored 2; patients with one and neither abnormality were scored 1 and 0, respectively. RESULTS: Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and platelet/lymphocyte ratio increased, whereas PNI and PMI decreased after CRT. There were 130, 73, and 22 patients in the PNSI 0, 1, and 2 groups, respectively. Patients with higher PNSI had higher residual tumor size (p = 0.003), yT stage (p = 0.007), ypStage (p < 0.001), post-CRT platelet/lymphocyte ratio (p = 0.027), and post-CRT C-reactive protein/albumin ratio (p < 0.001). Post-CRT PNSI was associated with overall survival and was an independent poor prognosis factor (PNSI 1 to 0, hazard ratio 2.40, p = 0.034, PNSI 2 to 0, hazard ratio 2.66, p = 0.043) together with mesenteric lymph node metastasis, lateral lymph node metastasis, and histology. CONCLUSION: A combined score of post-CRT malnutrition/sarcopenia is promising for predicting overall survival in LARC.

The robust performance of carcinoembryonic antigen levels after adjuvant chemotherapy for the recurrence risk stratification in patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: Most guidelines of colorectal cancers (CRCs) recommend evaluating the serum carcinoembryonic antigen (CEA) level during postoperative surveillance to detect tumor recurrence, which originates from postsurgery residual tumor cells. We hypothesized that the postadjuvant chemotherapy CEA level may be the most accurate biomarker to predict tumor recurrence, and we evaluated the prognostic significance of the postadjuvant chemotherapy CEA level in patients with stage II and III CRCs. PATIENTS AND METHODS: We retrospectively analyzed the cases of 150 Stage II-III CRC patients who had undergone curative surgery and adjuvant chemotherapy. Preoperative, postoperative, and postadjuvant chemotherapy CEA levels were evaluated, and their associations with recurrence-free survival (RFS) were assessed. RESULTS: The Kaplan-Meier curves showed that a high preoperative CEA level, high postoperative CEA, and high postadjuvant chemotherapy CEA were associated with poor RFS (p = .001, .0001, and .001, respectively). The multivariate analysis demonstrated that high postadjuvant chemotherapy CEA was an independent factor for poor RFS (HR 2.55, 95% confidence interval: 1.08-6.05, p = .033), whereas high preoperative and postoperative CEA levels were not. CONCLUSIONS: The serum levels of postadjuvant chemotherapy CEA were a strong prognostic biomarker in patients with Stage II-III CRCs who had undergone surgery followed by adjuvant chemotherapy.

Proposal for a post-operative surveillance strategy for stage I colorectal cancer patients based on a novel recurrence risk stratification: a multicenter retrospective study.

BACKGROUND: The recurrent risk of stage I colorectal cancer (CRC) is not clear, and the data regarding appropriate post-operative surveillance schedules in stage I CRC are scarce. OBJECTIVES: We aimed to stratify stage I CRC based on the recurrence risk and evaluate optimal post-operative surveillance durations based on this stratification. METHODS: We retrospectively analyzed the cases of 6607 stage I CRC patients from 24 institutions. To assess the patients' clinicopathological factors that impact recurrence-free survival (RFS), we performed univariate and multivariate analyses using Cox proportional hazards models. We divided the patients into classes based on their numbers of factors that were associated with poor RFI in the multivariate analysis. RESULTS: Recurrence occurred in 3.9% patients. The multivariate analysis revealed the independent factors for poor RFS: rectal cancer, T2 depth, presence of lymphatic invasion, high level of pre-operative carcinoembryonic antigen, and absence of D2-3 lymphadenectomy. We also divided the patients into three classes based on their numbers of these risk factors; the 3-year and 5-year RFS rates were 99.3% and 99.1% in the no-risk patients, 97.4% and 96.5% in the patients with 1-2 risks, and 92.1% and 90.0% in the patients with 3-5 risks, respectively. In the patients with no risk and in the patients with 1-2 risks after 3 years post-surgery, ≤ 1% recurrence occurred. Thus, post-operative surveillance may be omitted in these populations. CONCLUSIONS: Our new classification properly stratified the recurrence risks of stage I CRC patients, and may help reduce unnecessary post-operative surveillance.

Women are predisposed to early dose-limiting toxicities during adjuvant CAPOX for colorectal cancer.

AIM: Oxaliplatin-based adjuvant chemotherapy was demonstrated to be beneficial for stage III or high-risk stage II colorectal cancer (CRC). Moreover, a recent international collaborative trial suggested 3-months CAPOX as an alternative regimen for low-risk stage III colorectal cancer (CRC) patients. Thus, it is important to clarify the frequency and predictive markers of dose-limiting toxicities (DLTs) developed within the short-course CAPOX cycles. METHODS: We investigated CRC patients who underwent radical surgery and adjuvant CAPOX therapy at our hospital between December 2010 and February 2021. Patients who received initially reduced doses of CAPOX and those who had early recurrence were excluded. We reviewed the age, sex, comorbidities, physical, laboratory and oncological data and other perioperative factors. The associations between these variables and early DLTs within four cycles of CAPOX were examined by multivariate analyses using logistic regression models. RESULTS: Among 168 patients (96 men, mean age: 58.3 years), 120 (71%) developed early DLTs. Patients with early DLTs were predominantly women and sarcopenic and habitual alcohol consumers. On multivariate analyses, only the female sex was an independent predictive factor for early DLTs (odds ratio: 2.61, P = .027). CONCLUSION: Women were prone to early DLTs during adjuvant CAPOX in the current study. Doctors should be aware of the sex difference in the incidence of early DLTs, adjust the CAPOX dosage and provide supportive care for female CRC patients.

Outcomes of dogs with progressive myelomalacia treated with hemilaminectomy or with extensive hemilaminectomy and durotomy.

OBJECTIVE: To evaluate the ability of extensive hemilaminectomy and durotomy (EHLD) to control progressive myelomalacia (PMM) in dogs. STUDY DESIGN: Retrospective clinical study. ANIMALS: Twenty-eight client owned dogs that underwent EHLD (n = 10) or HL alone (n = 18). METHODS: After diagnosis by MRI, dogs were immediately treated with HL alone or EHLD at the site of intramedullary hyperintensity on T2-weighted (T2W)-MRI. Medical records were retrospectively reviewed. Follow-up data were collected via telephone interviews with the referring veterinarian and a standardized questionnaire. Postoperative survival outcome between groups was compared (log-rank test) by using Cox's proportional hazard analysis with baseline characteristics entered as covariates. RESULTS: The survival rate was higher in the EHLD group (P = .03) compared with the HL-alone group. Eleven of 18 dogs treated with HL survived, while seven of 18 dogs died (median, 5 days after surgery). In the EHLD group, 10 of 10 dogs survived postoperatively. Baseline characteristics were not associated with postoperative survival outcomes. According to multivariate analysis, EHLD was the independent factor associated with an increase in survival rate (P = .0002). CONCLUSION: EHLD durotomy at the intramedullary hyperintense region on T2W-MRI improved the survival rate of dogs with PMM compared with dogs treated with standard HL. CLINICAL SIGNIFICANCE: This study provides evidence that supports treatment with EHLD in dogs with PMM. Additional prospective studies are required.

The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer.

Accumulating evidence suggests that dysregulation of transcriptional enhancers plays a significant role in cancer pathogenesis. Herein, we performed a genome-wide discovery of enhancer elements in colorectal cancer (CRC). We identified PVT1 locus as a previously unrecognized transcriptional regulator in CRC with a significantly high enhancer activity, which ultimately was responsible for regulating the expression of MYC oncogene. High expression of the PVT1 long-non-coding RNA (lncRNA) transcribed from the PVT1 locus was associated with poor survival among patients with stage II and III CRCs (p < 0.05). Aberrant methylation of the PVT1 locus inversely correlated with the reduced expression of the corresponding the PVT1 lncRNA, as well as MYC gene expression. Bioinformatic analyses of CRC-transcriptomes revealed that the PVT1 locus may also broadly impact the expression and function of other key genes within two key CRC-associated signaling pathways - the TGFß/SMAD and Wnt/ß-Catenin pathways. We conclude that the PVT1 is a novel oncogenic enhancer of MYC and its activity is controlled through epigenetic regulation mediated through aberrant methylation in CRC. Our findings also suggest that the PVT1 lncRNA expression is a promising prognostic biomarker and a potential therapeutic target in CRC.

Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer.

PURPOSE: High neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. Preoperative NLR in colorectal cancer reportedly correlates with recurrence-free survival and is useful as a recurrence prediction factor. No reports have yet investigated recurrence factors using postoperative NLR. This study assessed the predictive value of NLR preoperatively and on the first (NLR1) and seventh day (NLR7) postoperatively in patients with stage II colorectal cancer. METHODS: We performed a retrospective cohort study involving patients undergoing colorectal resection at a single institution between January 2012 and December 2016; we used medical records of 176 consecutive patients with stage II colorectal cancer undergoing curative tumor resection. NLRs as well as clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with recurrence-free survival (RFS). RESULTS: Univariate analysis revealed that elevated NLR, NLR7, and lymphatic invasion were significantly associated with decreased RFS (p < 0.05). NLR7 was revealed as significant via multivariate analysis (p = 0.013). The 3-year RFS rate was 87.1% for patients with normal NLR7 and 70.3% for those with elevated NLR7. CONCLUSION: Elevated seventh-day postoperative NLR is a significant independent predictor of reduced RFS for patients with stage II colorectal cancer and may be a potential biomarker for identifying candidates for adjuvant chemotherapy.

A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes.

Most T1 colorectal cancers treated by radical surgery can now be cured by endoscopic submucosal dissection. Although 70%-80% of T1 colorectal cancers are classified as high risk, <16% of these patients actually have lymph node metastases. Biomarkers are needed to identify patients with T1 cancers with the highest risk of metastasis, to prevent unnecessary radical surgery. We collected data from The Cancer Genome Atlas and identified 5 microRNAs (MIR32, MIR181B, MIR193B, MIR195, and MIR411) with significant changes in expression in T1 and T2 colorectal cancers with vs without lymph node metastases. Levels of the 5 microRNAs identified patients with lymph node invasion by T1 or T2 cancers with an area under the receiver operating characteristic curve (AUROC) value of 0.84. We validated these findings in 2 cohorts of patients with T1 cancers, using findings from histology as the reference. The 5-microRNA signature identified T1 cancers with lymph node invasion in cohort 1 with an AUROC value of 0.83, and in cohort 2 with an AUROC value of 0.74. When we analyzed biopsy samples from untreated patients, the 5-microRNA signature identified cancers with lymph node metastases with an AUROC value of 0.77. The 5-microRNA therefore identifies high-risk T1 colorectal cancers with a greater degree of accuracy than currently used pathologic features.

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.

Application of convolutional neural networks for evaluating Helicobacter pylori infection status on the basis of endoscopic images.

BACKGROUND AND AIM: We recently reported the role of artificial intelligence in the diagnosis of Helicobacter pylori (H. pylori) gastritis on the basis of endoscopic images. However, that study included only H. pylori-positive and -negative patients, excluding patients after H. pylori-eradication. In this study, we constructed a convolutional neural network (CNN) and evaluated its ability to ascertain all H. pylori infection statuses. METHODS: A deep CNN was pre-trained and fine-tuned on a dataset of 98,564 endoscopic images from 5236 patients (742 H. pylori-positive, 3649 -negative, and 845 -eradicated). A separate test data set (23,699 images from 847 patients; 70 positive, 493 negative, and 284 eradicated) was evaluated by the CNN. RESULTS: The trained CNN outputs a continuous number between 0 and 1 as the probability index for H. pylori infection status per image (Pp, H. pylori-positive; Pn, negative; Pe, eradicated). The most probable (largest number) of the three infectious statuses was selected as the 'CNN diagnosis'. Among 23,699 images, the CNN diagnosed 418 images as positive, 23,034 as negative, and 247 as eradicated. Because of the large number of H. pylori negative findings, the probability of H. pylori-negative was artificially re-defined as Pn -0.9, after which 80% (465/582) of negative diagnoses were accurate, 84% (147/174) eradicated, and 48% (44/91) positive. The time needed to diagnose 23,699 images was 261 seconds. CONCLUSION: We used a novel algorithm to construct a CNN for diagnosing H. pylori infection status on the basis of endoscopic images very quickly. ABBREVIATIONS: H. pylori: Helicobacter pylori; CNN: convolutional neural network; AI: artificial intelligence; EGD: esophagogastroduodenoscopies.

Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers.

BACKGROUND: Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients. PATIENTS AND METHODS: We retrospectively investigated the clinicopathological data of 461 stage I-III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB- group), and we compared the two groups' recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets. RESULTS: The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB- group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB- group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset's stage I-III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023). CONCLUSION: ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.

G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer.

PURPOSE: The increased incidence of colorectal cancer (CRC) has necessitated the development of novel prognostic and predictive factors from which new diagnostic tests could evolve. Evidence suggests the KRAS gene represents such a factor; its mutations are considered to be early indicators of CRC progression. This study assessed the prognostic impact of specific known KRAS codon 12/13 mutations on survival in patients with CRC. METHODS: Formalin-fixed paraffin-embedded tissue blocks or sections from primary were obtained from patients registered between 2014 and 2016 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors. RESULTS: Sequencing of 200 CRC primary tumor samples demonstrated 74 (37.5%) with KRAS mutations in codons 12 (77%; 57/74) and 13 (23%; 17/74), all of which were TNM stages I-III. Tumors with KRAS mutations were more frequently located in the right side of the colon. Multivariate analysis indicated that G12V or G12C mutations were associated with poor prognosis [hazard ratio (HR) = 3.77, 95% confidence interval (CI), 1.54-8.39 and HR = 6.57; 95% CI, 1.90-17.7, respectively] in terms of recurrence-free survival. CONCLUSION: KRAS codon 12G-to-V or G-to-C mutations are independent prognostic factors in patients with stage I-III CRC.

A case of intussusception developed at the site of ileocolic anastomosis after laparoscopic right hemicolectomy.

BACKGROUND: Intussusception is a relatively common condition seen in children. In comparison, adult intussusception is rare and usually occurs as a complication in patients with organic diseases. It is responsible for 1% of all bowel obstructions, in most of intussusceptions a malignant tumor is involved. Herein, we present an extremely unusual case of intussusception that occurred as a complication at the site of a functional end-to-end anastomosis. CASE PRESENTATION: A 57-year-old female patient was diagnosed with tumors in the ascending and descending colon and was referred to our department. Laparoscopic hemicolectomy and laparoscopic descending colectomy were performed. The mechanical intestinal obstruction occurred on the 9th day postoperatively, and computed tomography scan revealed intussusception at the site of the ileocolic anastomosis. Endoscopic reduction was attempted, but the procedure was challenging. Surgery was then performed and revealed that the site of ileocolic anastomosis firmly adhered to the side wall and right retroperitoneum. However, the intestine in the oral side of the anastomosis was not fixed. Examination of the anastomotic site revealed that the ileum had passed through the anastomosis and prolapsed into the transverse colon. The ileocolic anastomosis was resected. End-to-end anastomosis was performed, and surgery was then completed. No neoplastic lesions were observed in the resected tissue of the lead point of intussusception. The postoperative clinical course was favorable, and the patient was discharged on the 11th day after the second round of surgery. CONCLUSIONS: There are no reports the anastomosis is involved as part of the intussception, as observed in the present case. Intussusception should thus be considered as one of the causes of postoperative mechanical intestinal obstruction.

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.