清島 亮

Objective: To validate the utility of recurrence prediction value (RPV) in identifying patients with UICC stage II colon cancer who would benefit from adjuvant chemotherapy (AC). Summary Background Data: The benefits of AC in Stage II colon cancer remain insufficient. Methods: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer who had undergone surgery. RPV was developed based on the weighting of each high-risk factor. Data from multi-institutional databases in Japan, the United States, and Jordan were used (cohort 1). In addition, nationwide data were obtained from Denmark (Cohort 2). The primary endpoint was recurrence-free survival (RFS). Results: According to the RPV, a low score was found in 750 (70.2%) patients and high scores in 318 (29.8%) patients in cohort 1. The corresponding numbers were 1031 (70.4%) and 433 (29.6%) patients in cohort 2, respectively. The five-year RFS rates were significantly higher in the group of patients who received AC than in the group who did not in the RPV high sub-group of cohort1 (76.2% vs. 55.6%, P <0.001) and in cohort2 (65.6% vs. 49.8%, P=0.001). Multivariate analyses revealed that AC was an independent prognostic factor for RFS only in the RPV high sub-group of both cohort 1 (hazard ratio (HR) 0.48; 95% confidence interval (CI) 0.29-0.81; P=0.005) and cohort2 (HR 0.69; 95% CI 0.48-0.99; P=0.043). Conclusions: This global study validates a readily available clinical data-based algorithm for predicting recurrence in Stage II colon cancer, identifying patients across diverse populations who benefit significantly from AC.

Background: Liver resection for colorectal liver metastases (CRLM) with concurrent extrahepatic disease (EHD) has demonstrated potential benefits for long-term prognosis; however, its effectiveness remains controversial. Additionally, the prognostic impact of different EHD sites is not well elucidated. This study aimed to assess the significance of liver resection in patients with CRLM with concurrent EHD and evaluate how different EHD sites influence prognosis. Methods: A nationwide multicenter database was used for a retrospective analysis of patients diagnosed during two periods: 2005–2007 and 2013–2015. EHD was classified into the following five subgroups: lung, peritoneum, lymph nodes, local, and others. The inverse probability of treatment weighting (IPTW) method was applied to minimize selection bias. Kaplan–Meier survival curves and Cox proportional hazards models were used to compare the overall survival (OS) between the different treatment groups and EHD subgroups. Results: Among 3,787 patients, 874 (23.1%) underwent liver resection. Following IPTW adjustment, the hepatectomy (HT) group demonstrated significantly better OS than the non-hepatectomy (non-HT) group (5-year hazard ratio, 0.322; 95% confidence interval, 0.273–0.379; p < 0.001). Analysis by the EHD site subgroup demonstrated that liver resection was associated with a better prognosis across all sites. However, the prognostic impact differed by EHD site, with peritoneal metastasis associated with poorer outcomes in both the HT (5-year OS rates, 30.1% vs. 45.0%) and non-HT (5-year OS rates, 4.4% vs. 8.6%) groups. Conclusions: Regardless of the EHD site, liver resection was associated with a significantly better OS in patients with CRLM with concurrent EHD. The prognostic impact varies across EHD sites, underscoring the significance of considering differential prognostic risks when selecting treatment strategies.

ABSTRACT Aim This study evaluated the short‐term outcomes of low anterior resection for rectal cancer in Japan before and after the COVID‐19 pandemic, with a particular focus on the timing of its reclassification within Japan in May 2023. Methods Using data from the Japanese National Clinical Database, we analyzed 109 754 low anterior resection cases between January 2018 and December 2023, categorized into pre‐pandemic (February 2020 and earlier), pandemic (March 2020–April 2023), and post‐pandemic (May 2023 onward) periods. Trends in the number of low anterior resection cases, postoperative intensive care unit utilization, and complications, including anastomotic leakage and pneumonia, were examined. Standardized morbidity ratios were used to adjust for risk and assess trends over time. Results The number of low anterior resection cases declined during the pandemic but returned to pre‐pandemic levels thereafter. The postoperative intensive care unit admission rates remained stable, with a slight increase post‐pandemic. The incidence of major complications gradually declined from pre‐pandemic to post‐pandemic, with anastomotic leakage rates decreasing from 9.8% to 7.1% and the standardized morbidity ratio for anastomotic leakage decreasing from 1.0 to 0.8, reflecting improved outcomes. The number of robot‐assisted surgeries significantly increased from 246 cases in March 2020 to 535 in May 2023, and their proportion among total surgeries also rose from 16.8% to 41.2%. Conclusion Despite initial challenges, the healthcare system of Japan effectively managed rectal cancer surgeries during and after the pandemic. Robotic surgery became more widely adopted, and complication rates improved, demonstrating resilience and adaptability in surgical care.

BACKGROUND: Extended colectomy is considered standard treatment for neoplasia associated with ulcerative colitis, but there is limited supporting evidence, particularly from large-scale studies. OBJECTIVE: This study aimed to assess the prognostic benefits of extended colectomy in patients with neoplasia associated with ulcerative colitis using a nationwide database. DESIGN: Multicenter retrospective study. SETTINGS: Forty-three institutions in Japan participated in this study. PATIENTS: Patients with ulcerative colitis diagnosed with intestinal neoplasia between 1983 and 2020 at 43 institutions were analyzed. MAIN OUTCOME MEASURES: Five-year overall survival and disease-free survival were assessed based on different surgical procedures, with a subgroup analysis comparing neoplasia associated with ulcerative colitis to sporadic cancer. RESULTS: Among 879 patients, 801 were diagnosed with neoplasia associated with ulcerative colitis and 78 with sporadic cancer. The 5-year disease-free survival for total proctocolectomy and subtotal colectomy were similar (87.8% and 83.9%), both superior to segmental colectomy (72.0%). When comparing neoplasia associated with ulcerative colitis to sporadic cancer, extended colectomy (total proctocolectomy and subtotal colectomy) showed significantly better outcomes for neoplasia associated with ulcerative colitis, while no significant difference was observed for sporadic cancer. Multivariable analysis revealed a significantly better prognosis for extended colectomy compared to segmental colectomy in neoplasia associated with ulcerative colitis patients, both in overall survival and disease-free survival (P < 0.001). LIMITATION: Nonrandomized retrospective study design. CONCLUSION: This nationwide cohort study supports extended colectomy as the gold standard for neoplasia associated with ulcerative colitis management and underscores the importance of accurate diagnosis to distinguish between neoplasia associated with ulcerative colitis and sporadic cancer for optimal treatment decisions. See Video Abstract.

PURPOSE: This study aimed to investigate the effects of the coronavirus disease 2019 pandemic on morbidity and mortality after advanced hepatectomy by surgical volume in Japan. METHODS: Data from patients who underwent advanced hepatectomy between 2018 and 2022 from the Japanese National Clinical Database were collected. The transition of the number of hepatectomies and changes in risk-adjusted mortality and major complication rates based on the type of institutions certified by the Japan Society of Hepato-Biliary-Pancreatic Surgery were investigated. RESULTS: A total of 33 454 cases were included. The number of advanced hepatectomies gradually decreased, whereas the proportion of hepatectomies performed in certified institutions increased (from 63.4% in 2018 to 71.3% in 2022). Although the major complication rate in institution A was higher than that in institution B or noncertified institutions (16.3% vs. 14.5% vs. 13.5%), the in-hospital mortality rate was consistently favorable in the order of institution A, institution B, and noncertified institutions (1.4% vs. 2.0% vs. 2.8%). The monthly standardized mortality and major complication ratios did not significantly increase mostly throughout the pandemic, regardless of the institution type. CONCLUSIONS: The centralization to certified institutions progressed even during the pandemic. Surgical safety after advanced hepatectomy was satisfactorily maintained in any institution.

BACKGROUND: Colorectal cancer (CRC) is a substantial global health concern due to its limited treatment options, especially for oxaliplatin (L-OHP) regimen resistance. This study used organoid-based screening methodologies to evaluate drug responses in CRC while validating the approach with patient-derived CRC organoids and investigating potential biomarkers. METHODS: Patient-derived organoids were created from CRC surgical specimens, and drug screening were performed. Selected organoids with high and low L-OHP sensitivity underwent next-generation sequencing (NGS), and in vivo experiments using xenotransplantation were used to validate in vitro results. Moreover, the clinical application of homologous recombination deficiency (HRD) as a biomarker was investigated. RESULTS: Organoid drug screening revealed differences in L-OHP sensitivity among 34 patient-derived CRC organoids, and NGS deemed HRD as a potential biomarker. In vivo experiments validated the correlation between HRD status and L-OHP sensitivity, and clinical data suggested the potential of HRD as a biomarker for recurrence-free survival in patients treated with L-OHP. Additionally, HRD exhibited potential as a biomarker for other platinum agents and poly (ADP-ribose) polymerase inhibitors in CRC. CONCLUSIONS: The study underscores HRD as a potential biomarker for predicting L-OHP sensitivity, expanding its application to other drugs in CRC. Organoid screening is reliable, providing insights into the intricate association between genetic features and treatment responses.

Abstract Nanospace has been used as a specific field for syntheses and assemblies of molecules, polymers, and materials. Free volume space among polymer chains is related to their properties, such as permeation of gas and small molecules. However, the void has not been used as a functional nanospace in previous works. The present work shows synthesis of guest conductive polymers in free volume space of conventional synthetic resins and rubbers as a new nanospace. Vapor of heteroaromatic monomer and oxidative agent is diffused into the soft dynamic nanospace among the polymer chains under ambient pressure at low temperature. The oxidative polymerization provides the conductive polymers, such as polypyrrole (PPy), in the free volume space of poly(methyl methacrylate) (PMMA), polypropylene (PP), silicone rubber (SR), and polyurethane rubber (PU). The ratio of the free volume decreases with the infiltration of the conductive polymers. The composites exhibit the improved mechanical and gas barrier properties. The rubbers containing PPy are used as mechanical‐stress sensors with both the conductivity and flexibility. The free volume space of resins and rubbers can be used as a new dynamic nanospace for synthesis of functional polymer composites.

ABSTRACT Introduction In this randomized controlled trial, we compared the effectiveness of Toraysee for ES (Toray, Tokyo, Japan), a microfiber cleaning cloth composed of ultrafine polyester fibers, with that of a conventional lens‐cleaning method during laparoscopic colorectal surgery. Methods Patients scheduled for laparoscopic colorectal surgery were randomly allocated to a microfiber cleaning cloth or a conventional lens‐cleaning arm. The primary outcome was the mean time spent on each occasion of lens cleaning. Visual quality was evaluated objectively by using visual analyzing software. Results Sixty patients consented to participation in this study, and the data of 55 patients were analyzed. The mean time spent on each occasion of lens cleaning was significantly shorter in the microfiber cloth group than in the control group (16.12 ± 4.63 vs. 21.04 ± 4.83, p &lt; 0.01). Despite the shorter cleaning time, the median difference in clarity score between before and after each cleaning occasion did not differ significantly between the groups (0.164 vs. 0.135, p = 0.276). Conclusions Toraysee microfiber cleaning cloths are easy and time efficient lens‐cleaning devices while achieving a visual quality equivalent compared to a conventional cleaning method.

Objectives Lockdowns and outing restrictions during the COVID-19 pandemic may have altered attitudes towards hospital visits. This study aimed to investigate changes in long-distance visits outside of secondary healthcare service areas (SHSA) among cancer patients in Japan. Design Retrospective observational study. Setting Inpatient data from the Japanese Diagnosis Procedure Combination database. Primary and secondary outcome measures We retrospectively analysed inpatient data from January 2018 to December 2021, extracted from the Japanese Diagnosis Procedure Combination database. The study examined whether the patient’s hospital was within their residence’s SHSA and compared the admission rates before and after the pandemic. Results The data of a total of 2 394 760 patients were analysed. Admission rates outside the SHSA significantly decreased after the pandemic compared with prepandemic years (26.67% and 27.58%, respectively, p&lt;0.001). Significant reductions were observed in nearly all age groups over 30 years old, but not in younger ones. Characteristics of patients’ residences, including COVID-19 infection rates, population density and the number of regional cancer hospitals, were also influential factors. The cancer site was a significant factor, with the respiratory system showing a 3.77% decrease, particularly a 5.29% decrease in those who needed surgeries that are not highly specialised (p&lt;0.001). Conclusions Admission to distant hospitals among cancer patients decreased following the COVID-19 pandemic, indicating a restraint in their behaviour of visiting distant hospitals. The appropriate allocation of specialised hospitals will serve as a measure for the next pandemic.

BACKGROUND: The COVID-19 pandemic had a profound impact on cancer screening, diagnosis, and treatment procedures. We speculated that during the COVID-19 pandemic, sufficient medical resources were maintained in board-certified hospitals, resulting in favorable short-term outcomes, whereas hospital functions in non-board-certified hospitals declined, leading to mortality increase. The aim of this study is to investigate the impact of COVID-19 pandemic on short-term outcomes after esophagectomy, based on the scale of the facilities. METHODS: Data of patients who underwent esophagectomy for esophageal cancer between January 2018 and December 2022 were analyzed using the National Clinical Database (NCD) of Japan. We selected the Authorized Institutes for Board-certified Esophageal Surgeons (AIBCESs) certified by the Japan Esophageal Society (JES) at the hospital level for evaluating the difference in outcomes between institutions. Operative mortality rates and other morbidities were evaluated using the standardized mortality and morbidity ratio (SMR, the ratio of the number of observed patients to the expected number of patients). RESULTS: Within the study period, the annual mean operative mortality rate was higher in non-AIBCESs than in AIBCESs. The SMR showed no significant difference after the COVID-19 pandemic in non-AIBCES for mortality, as well as that in AIBCES. CONCLUSIONS: In non-AIBCESs, no worsening of results caused by the COVID-19 pandemic was observed despite the shortage of medical resources. Our findings highlighted the high quality of esophageal surgery in Japan during the COVID-19 pandemic, a critical situation with limited medical resources.

Abstract Aim To investigate the relationship between the three timepoint perioperative CEA (ttpCEA) calculated at three timepoints and recurrence during the perioperative period in Stage II and III colorectal cancer (CRC) patients. Methods We performed a multi‐institutional retrospective analysis of patients with Stage II and III CRC who underwent surgery and adjuvant chemotherapy from 2010 to 2020. Patient data from three facilities were used as training data, and data from three other facilities were used as validation data. The primary endpoint was the time to recurrence (TTR). Results A total of 538 patients were included for the training data. To validate the feasibility of ttpCEA, 329 patients were included for the validation data. Training data patients were categorized as ttpCEA low (n = 365) and ttpCEA high (n = 173). The 5‐y TTR was significantly greater in the ttpCEA‐low subgroup than in the ttpCEA‐high subgroup (84.3% vs. 69.6%, respectively; p &lt; 0.001). Validation data patients were categorized as ttpCEA low (n = 221) and ttpCEA high (n = 108). The 5‐y TTR was significantly greater in the ttpCEA‐low subgroup than in the ttpCEA‐high subgroup (82.9% vs. 68.7%, respectively; p = 0.003). Conclusion The ttpCEA calculated from perioperative CEA levels at different timepoints was a prognostic factor for recurrence in Stage II and III CRC patients who underwent adjuvant chemotherapy according to both the training and validation data.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

AIM: Serum cholinesterase (ChE) levels are considered to reflect nutritional status. Although ChE has been well documented as a prognostic factor for some cancers, no clear consensus on its use for colorectal cancer (CRC) has been reached. The aim of this study was to investigate the relationship between preoperative serum ChE and postoperative long-term prognosis in CRC patients. METHODS: A total of 1053 CRC patients who underwent curative surgery were included in this study. The correlations between the preoperative ChE value and overall survival (OS) or cancer-specific survival (CSS) were assessed. By dividing patients into two groups according to their ChE value, OS and CSS were compared between the groups. RESULTS: Multivariate analysis revealed that the continuous ChE value was a significant predictor of OS (hazard ratio, 0.996; 95% CI, 0.993-0.998; p = 0.002) and CSS (hazard ratio, 0.994; 95% CI, 0.991-0.998; p = 0.001), independent of other variables. The low-ChE (≤234 U/L) group had a significantly poorer prognosis than the high-ChE (>234 U/L) group for both OS (5-year OS for low ChE and high ChE: 79.8% and 93.3%, respectively; p < 0.001) and CSS (5-year CSS for low ChE and high ChE: 84.8% and 95.6%, respectively; p < 0.001). CONCLUSIONS: Lower preoperative serum ChE levels are a predictive factor of poor prognosis for CRC patients. As serum ChE levels can be measured quickly and evaluated easily, ChE could become a useful marker for predicting the postoperative long-term outcomes of CRC patients.

BACKGROUND: In patients with colorectal cancer, both the C-reactive protein–to-albumin ratio and comprehensive risk score of the estimation of physiologic ability and surgical stress have demonstrated prognostic significance. OBJECTIVE: To assess the clinical value of the combined use of C-reactive protein–to-albumin ratio and comprehensive risk score for predicting prognosis in patients with colorectal cancer. DESIGN: Multicenter retrospective study. SETTINGS: The cohort was divided into 3 groups based on a combined score derived from the value of C-reactive protein–to-albumin ratio and comprehensive risk score (low/mid/high). PATIENTS: Patients who underwent curative resection between 2010 and 2019 at multiple institutions were enrolled in this study. MAIN OUTCOME MEASURES: Overall and recurrence-free survival. RESULTS: A total of 2207 patients (801 in the low cohort, 817 in the mid cohort, and 589 in the high cohort) were included in this study. Multivariate analysis revealed that combined score was an independent prognostic factor for both overall and recurrence-free survival, irrespective of disease stage (p &lt; 0.05). Furthermore, Harrell’s C-index indicated that the predictive power of the combined score was significantly superior to that of the C-reactive protein–to-albumin ratio or comprehensive risk score (p &lt; 0.001). LIMITATIONS: This study had a retrospective design, and data on genetic markers were not included. CONCLUSIONS: The synergistic combination of C-reactive protein–to-albumin ratio and comprehensive risk score contributes to the robust definition of combined score, a potent prognostic factor, regardless of disease stage. This finding has the potential to provide novel insights into the management of patients with colorectal cancer who have undergone curative resection. See the Video Abstract. LA PUNTUACIÓN COMBINADA DE RIESGO INTEGRAL DE LA ESTIMACIÓN DE LA CAPACIDAD FISIOLÓGICA Y EL ESTRÉS QUIRÚRGICO Y LA RELACIÓN PROTEÍNA C REACTIVA/ALBÚMINA ES UN FUERTE INDICADOR PRONÓSTICO DE LOS RESULTADOS A LARGO PLAZO EN EL CÁNCER COLORRECTAL ANTECEDENTES: En pacientes con cáncer colorrectal, tanto la relación proteína C reactiva/albúmina como la puntuación de riesgo integral de la Estimación de la capacidad fisiológica y el estrés quirúrgico han demostrado importancia pronóstica. OBJETIVO: Evaluar el valor clínico del uso combinado de la relación proteína C reactiva/albúmina y la puntuación de riesgo integral para predecir el pronóstico en pacientes con cáncer colorrectal. DISEÑO: Estudio retrospectivo multicéntrico. AJUSTES: La cohorte se dividió en tres grupos según una puntuación combinada derivada del valor de la relación proteína C reactiva/albúmina y la puntuación de riesgo integral (bajo/medio/alto). PACIENTES: En este estudio se inscribieron pacientes que se sometieron a resección curativa entre 2010 y 2019 en múltiples instituciones. PRINCIPALES MEDIDAS DE VALORACIÓN: Supervivencia general y libre de recurrencia. RESULTADOS: En este estudio se incluyeron un total de 2207 pacientes (801 en la cohorte baja, 817 en la cohorte media y 589 en la cohorte alta). El análisis multivariado reveló que la puntuación combinada fue un factor pronóstico independiente tanto para la supervivencia general como para la supervivencia libre de recurrencia, independientemente del estadio de la enfermedad (p &lt;0,05). Además, el índice C de Harrell indicó que el poder predictivo de la puntuación combinada era significativamente superior al de la relación proteína C reactiva-albúmina o a la puntuación de riesgo integral (p &lt;0,001). LIMITACIONES: Este estudio tuvo un diseño retrospectivo y no se incluyeron datos sobre marcadores genéticos. CONCLUSIÓN: La combinación sinérgica de la relación proteína C reactiva/albúmina y la puntuación de riesgo integral contribuye a la definición sólida de la puntuación combinada, un potente factor pronóstico, independientemente del estadio de la enfermedad. Este hallazgo tiene el potencial de proporcionar conocimientos novedosos sobre el tratamiento de pacientes con CCR sometidos a resección curativa. (Traducción— Dr. Ingrid Melo)

Abstract Background Due to the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening, diagnosis, and treatment have changed. This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection prior to gastroenterological cancer surgeries on postoperative complications using data from a nationwide database in Japan. Methods Data on patients who underwent surgery for cancer including esophageal, gastric, colon, rectal, liver, and pancreatic cancer between July 1, 2019, and September 300, 2022, from real‐world sources in Japan were analyzed. The association between preoperative SARS‐CoV‐2 infection and short‐term postoperative outcomes was evaluated. A similar analysis stratified according to the interval from SARS‐CoV‐2 infection to surgery (&lt;4 vs. &gt;4 weeks) was conducted. Results In total, 60 604 patients were analyzed, and 227 (0.4%) patients were diagnosed with SARS‐CoV‐2 infection preoperatively. The median interval from SARS‐CoV‐2 infection to surgery was 25 days. Patients diagnosed with SARS‐CoV‐2 infection preoperatively had a significantly higher incidence of pneumonia (odds ratio: 2.05; 95% confidence interval: 1.05–3.74; p = 0.036) than those not diagnosed with SARS‐CoV‐2 infection based on the exact logistic regression analysis adjusted for the characteristics of the patients. A similar finding was observed in patients who had SARS‐CoV‐2 infection &lt;4 weeks before surgery. Conclusions Patients with a history of SARS‐CoV‐2 infection had a significantly higher incidence of pneumonia. This finding can be particularly valuable for countries that have implemented strict regulations in response to the COVID‐19 pandemic and have lower SARS‐CoV‐2 infection‐related mortality rates.

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>The coronavirus disease 2019 (COVID‐19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Data on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>This study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID‐19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien–Dindo grade ≥4 complications, and the 30‐day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID‐19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID‐19 pandemic.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The increasing trend in the number of pancreaticoduodenectomies and favorable short‐term outcomes even in the COVID‐19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.</jats:p></jats:sec>

Abstract Mechanoresponsive materials have been studied to visualize and measure stresses in various fields. However, the high‐sensitive and spatiotemporal imaging remain a challenging issue. In particular, the time evolutional responsiveness is not easily integrated in mechanoresponsive materials. In the present study, high‐sensitive spatiotemporal imaging of weak compression stresses is achieved by time‐evolutional controlled diffusion processes using conjugated polymer, capsule, and sponge. Stimuli‐responsive polydiacetylene (PDA) is coated inside a sponge. A mechanoresponsive capsule is set on the top face of the sponge. When compression stresses in the range of 6.67–533 kPa are applied to the device, the blue color of PDA is changed to red by the diffusion of the interior liquid containing a guest polymer flowed out of the disrupted capsule. The applied strength (F/N), time (t/s), and impulse (F·t/N s) are visualized and quantified by the red‐color intensity. When a guest metal ion is intercalated in the layered structure of PDA to tune the responsivity, the device visualizes the elapsed time (τ/min) after unloading the stresses. PDA, capsule, and sponge play the important roles to achieve the time evolutional responsiveness for the high‐sensitive spatiotemporal distribution imaging through the controlled diffusion processes.

Colorectal mucinous adenocarcinoma (MAC) is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC). This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs) between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

AIM: The Coronavirus Disease 2019 (COVID-19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short-term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. METHODS: Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID-19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). RESULTS: This study included 74 181 patients, including 43 663 (58.9%) from COVID-19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30-day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. CONCLUSION: Although the pandemic temporarily decreased the ICU admission rate, its impact on short-term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.

BACKGROUND: Osteopenia, a condition in which bone mineral density is lower than normal, is a noted risk factor that leads to a shortened healthy life expectancy. OBJECTIVE: To investigate the prognostic impact of preoperative osteopenia in patients with colorectal cancer. DESIGN: This was a retrospective study. SETTING: This study was conducted at a university hospital. PATIENTS: A total of 1086 patients with stage I to III colorectal cancer who underwent curative resection. MAIN OUTCOME MEASURES: Osteopenia was evaluated with CT. Overall survival, disease-specific survival, and recurrence-free survival were the primary end points. RESULTS: Osteopenia was identified in 300 patients (27.6%). Compared with the no osteopenia group, the 5-year overall survival (74.0% vs 93.4%, p < 0.001), disease-specific survival (81.6% vs 97.2%, p < 0.001), and recurrence-free survival rates (57.1% vs 88.3%, p < 0.001) were significantly lower in the osteopenia group. Multivariate analyses showed that preoperative osteopenia was significantly associated with worse overall survival (HR: 4.135; 95% CI, 2.963-5.770; p < 0.001), disease-specific survival (HR: 7.673; 95% CI, 4.646-12.675; p < 0.001), and recurrence-free survival (HR: 5.039; 95% CI, 3.811-6.662; p < 0.001). The prognosis of the osteopenia group was poorer than that of the no osteopenia group in every stage: 5-year overall survival (stage I: 89.4% vs 96.9%, p = 0.028; stage II: 76.5% vs 91.9%, p < 0.001; stage III: 56.4% vs 90.8%, p < 0.001) and 5-year recurrence-free survival (stage I: 85.4% vs 96.6%, p = 0.002; stage II: 62.0% vs 86.5%, p < 0.001; stage III: 26.4% vs 80.0%, p < 0.001). LIMITATIONS: The main limitations are retrospective single-institutional features and races of the study population. CONCLUSIONS: Preoperative osteopenia could be a strong predictive marker for long-term prognosis in colorectal cancer regardless of stage. EL IMPACTO PRONSTICO DE LA OSTEOPENIA PREOPERATORIA EN PACIENTES CON CNCER COLORRECTAL: ANTECEDENTES:La osteopenia, una afección en la que la densidad mineral ósea es más baja de lo normal, es un relevante factor de riesgo que conduce a una expectativa menor de vida saludable.OBJETIVO:Investigar el impacto pronóstico de la osteopenia preoperatoria en pacientes con cáncer colorrectal (CCR).DISEÑO:Un estudio retrospectivo.AJUSTE:Estudio realizado en un hospital universitario.PACIENTES:Un total de 1.086 pacientes con CCR en estadio I-III sometidos a una resección curativa.PRINCIPALES MEDIDAS DE RESULTADO:La osteopenia se evaluó con imágenes de tomografía computarizada. La supervivencia global la supervivencia específica de la enfermedad y la supervivencia libre de recurrencia fueron los criterios de valoración primaria.RESULTADOS:Se identificó osteopenia en 300 pacientes (27,6%). En comparación con el grupo sin osteopenia, las tasas de supervivencia global a 5 años (74,0% frente a 93,4%, p < 0,001), supervivencia especifica de la enfermedad (81,6 % frente a 97,2%, p < 0,001) tasas de supervivencia libre de recurrencia (57,1% frente a 88,3%, p < 0,001) fueron significativamente más bajas en el grupo de osteopenia. Los análisis multivariados mostraron que la osteopenia preoperatoria se asoció significativamente con una peor supervivencia global (HR 4,135; IC 95% 2,963-5,770; p < 0,001), supervivencia especifica de la enfermedad (HR 7,673; IC 95% 4,646-12,675; p < 0,001) y tasas de supervivencia libre de recurrencia (HR 5,039; IC 95% 3,811-6,662; p < 0,001). El pronóstico del grupo con osteopenia fue peor que el del grupo sin osteopenia en todos los estadios: supervivencia global a 5 años (estadio I: 89,4% frente a 96,9%, p = 0,028; estadio II: 76,5% frente a 91,9%, p < 0,001; estadio III: 56,4% frente a 90,8%, p < 0,001) y tasas de supervivencia libre de recurrencia a 5 años (estadio I: 85,4% frente a 96,6%, p < 0,002; estadio II: 62,0% frente a 86,5%, p < 0,001; estadio III: 26,4% frente a 80,0%, p < 0,001).LIMITACIONES:Las principales limitaciones son las características retrospectivas de una sola institución y las razas de la población de estudio.CONCLUSIONES:La osteopenia preoperatoria puede ser un fuerte marcador predictivo para el pronóstico a largo plazo en CCR independientemente de la etapa. (Traducción-Dr. Fidel Ruiz Healy ).

PURPOSE: The number of patients with late-onset ulcerative colitis (UC) requiring surgery has increased in recent years. The risk of postoperative complications is higher in the elderly, so preoperative assessment is important. We aimed to explore the performance of preoperative assessment of nutritional markers for predicting postoperative complications in patients with late-onset UC. METHODS: We retrospectively analysed 140 medically refractory UC patients who underwent surgery. The association between age at UC onset and risk of postoperative complications was explored using a fractional polynomial model. Uni- and multi-variate logistic regression analyses were performed to identify nutritional markers associated with postoperative complications. RESULTS: The polynomial model showed patients with UC onset after 50 years of age had an increased risk of postoperative complications. Late-onset (LO) UC, an onset occurring after 50 years old, was associated with a higher risk of incisional surgical site infection (SSI) and intra-abdominal abscess than early-onset (EO) UC. Compared with the EO group, the LO group had fewer nutritional markers that were significantly associated with postoperative complications. The prognostic nutritional index (PNI) was calculated using the albumin level and the total lymphocyte count, and it was the only index that was significant in the LO group (odds ratio 0.872 95% CI 0.77-0.99, P = 0.03). CONCLUSIONS: It was more difficult to use nutritional status to predict the risk of postoperative complications in patients with late-onset UC than in patients with early-onset ulcerative colitis. PNI may be a useful nutritional marker for patients with both late- and early-onset UC.

BACKGROUND: It is unclear how early- and delayed-onset organ/space surgical site infections (SSIs) affect the long-term prognosis of patients with colorectal cancer, who are potential candidates for adjuvant chemotherapy. This study aimed to investigate the association between the timing of SSI onset and clinical outcome. METHODS: This retrospective, multicenter cohort study evaluated patients who were diagnosed with high-risk stage II or III colorectal cancer and underwent elective surgery between 2010 and 2020. Five-year recurrence-free survival (RFS) was the primary endpoint and was compared between early SSI, delayed SSI (divided based on the median date of SSI onset), and non-SSI groups. RESULTS: A total of 2,065 patients were included. Organ/space SSI was diagnosed in 91 patients (4.4%), with a median onset of 6 days after surgery. The early-onset SSI group had a higher proportion of patients with Clavien-Dindo grade ≥IIIb SSI than the delayed-onset SSI. Patients who received adjuvant chemotherapy (AC) had earlier organ/space SSI onset than those who did not. The adjusted hazard ratio of 5-year RFS in the delayed-onset SSI was 2.58 (95% confidence interval: 1.43-4.65; p = 0.002): higher than that in the early-onset SSI, with the non-SSI as the reference. CONCLUSIONS: Delayed-onset organ/space SSI worsened long-term prognosis compared to early-onset, and this may be due to delayed initiation of AC. Patients who are clinically suspected of having lymph node metastasis might need additional intervention to prevent delays in commencing AC due to the delayed SSI.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

AIM: The splenic flexure has variable vascular anatomy, and the details of the venous forms are not known. In this study, we report the flow pattern of the splenic flexure vein (SFV) and the positional relationship between the SFV and arteries such as the accessory middle colic artery (AMCA). METHODS: This was a single-centre study using preoperative enhanced CT colonography images of 600 colorectal surgery patients. CT images were reconstructed into 3D angiography. SFV was defined as a vein flowing centrally from the marginal vein of the splenic flexure visible on CT. AMCA was defined as the artery feeding the left side of the transverse colon, separate from the left branch of the middle colic artery. RESULTS: The SFV returned to the inferior mesenteric vein (IMV) in 494 cases (82.3%), the superior mesenteric vein in 51 cases (8.5%) and the splenic vein in seven cases (1.2%). The AMCA was present in 244 cases (40.7%). The AMCA branched from the superior mesenteric artery or its branches in 227 cases (93.0% of cases with existing AMCA). In the 552 cases in which the SFV returned to the IMV, superior mesenteric vein or splenic vein, the left colic artery was the most frequent artery accompanying the SFV (42.2%), followed by the AMCA (38.1%) and the left branch of the middle colic artery (14.3%). CONCLUSIONS: The most common flow pattern of the vein in the splenic flexure is from the SFV to IMV. The SFV is frequently accompanied by the left colic artery or AMCA.

BACKGROUND: The number of lymph node metastasis (LNM) is a strong prognostic factor in the treatment of colorectal cancer (CRC). However, the impact of the mesentery location on LNM remains unclear. We assessed the impact LNM location on the recurrence of stage III CRC. METHODS: Subjects with CRC and pathologically positive LNM were enrolled retrospectively. We defined three groups: LNM adjacent to the tumour (group A), metastases with horizontal or vertical spread (group B), and metastases with both horizontal and vertical spread (group C). Recurrence-free survival (RFS) was the primary outcome measure used for the study. RESULTS: A total of 241 (Group A: 121, B: 90, and C: 30) patients were recruited for the study. Multivariate analysis by Cox regression model indicated LNM location to be an independent predisposing risk factor for recurrence [group B: Hazard ratio (HR) 2.01, 95% Confidential interval (CI) 1.12-3.60, P = 0.019; group C: HR 3.00, 95% CI 1.34-6.72, P = 0.008]. Addition of mesentery spread to the N classification was significant risk factor for recurrence (mN2a: HR 2.01, 95% CI 1.07-3.78, P = 0.029; mN2b: HR 3.96, 95% CI 2.12-7.40, P < 0.01). Comparison of Harrell's C-index values was conducted, and the modified N staging risk was 0.6377, whereas the TNM N stage classification was 0.5869. CONCLUSION: Mesentery location of LNM was a risk factor and consideration of it might be beneficial for accurate prediction of CRC prognosis.

BACKGROUND: Although extended lymph node dissection during colon cancer surgery is recommended in both Western and Eastern countries, the perception and clinical significance of main lymph node metastasis (MLNM) remains controversial. METHODS: In total, 1557 patients with colon cancer who underwent curative resection with D3 dissection were retrospectively analyzed. Clinicopathological factors associated with MLNM were analyzed. Kaplan-Meier survival analysis and log-rank tests were used to compare the prognosis between the MLNM and non-MLNM groups. RESULTS: Multivariate analysis showed that overall survival (OS) [hazard ratio, 2.117 (0.939-4.774), p = 0.071] and recurrence-free survival (RFS) [hazard ratio, 2.183 (1.182-4.031), p = 0.013] were affected by the MLNM status independent of the TNM stage. Survival analysis demonstrated that among patients with stage III disease, the OS and RFS rates were significantly different between patients with and without MLNM (OS: p = 0.0147, RFS: p = 0.0001). However, the OS and RFS rates were not significantly different between patients who had stage III disease with MLNM and patients who had stage IV disease (OS: p = 0.5901, RFS: p = 0.9610). CONCLUSIONS: MLNM is an independent prognostic factor for patients with colon cancer. The addition of the MLNM status to the current TNM classification may enhance the prognostic value of the TNM staging system and the clinical efficacy of adjuvant therapy in patients with colon cancer.

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 &lt; 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 &lt; 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.

Abstract Imaging and measuring compression stresses secure a safe and healthy life. Compression stresses in kPa range are not easily detected by conventional mechanoresponsive materials because microscopic molecular motion of the chromophores is not induced by such weak stresses. Moreover, imaging of the stress distribution is not achieved so far. The present study shows a sponge device combining two stimuli‐responsive materials, a capsule releasing interior liquid and color‐changing polymer in responses to compression stress and chemical stimulus, respectively. The stimuli‐responsive capsule is dispersed on a melamine sponge comprised of the fibers with coating the layered polydiacetylene (PDA). The application of weak compression stresses induces collapse of the capsules, outflow of the interior liquid, and subsequent irreversible color change of PDA. The cascading response in the sponge device colorimetrically enables imaging of the distribution and measuring the strength of the compression stresses in kPa range. Furthermore, the device demonstrates imaging and measuring unknown weak compression stresses applied by the irregular‐shaped objects. A couple of clinical issues in surgical operation of intestine are studied using the stress‐imaging sponge device. The device and its design strategy can be applied to stress imaging in a variety of fields.

BACKGROUND/AIM: STAT3 is involved in the progression of several cancers, and has been proposed as target for therapy. Indeed, the multitargeted tyrosine kinase inhibitor drug regorafenib, which indirectly inhibits STAT3, can significantly enhance the effects of anti-programmed death receptor (PD)-1 therapy in hepatocellular carcinoma (HCC) models. Here, we studied the impact of a direct STAT3 inhibitor on the tumor microenvironment and PD-1 blockade efficacy in HCC models. MATERIALS AND METHODS: Orthotopic mouse models of HCC (RIL-175 and HCA-1 grafts in syngeneic mice) were used to test the efficacy of the selective STAT3 inhibitor STX-0119 alone or combined with anti-PD-1 antibodies. We evaluated the effects of therapy on tumor vasculature and the immune microenvironment using immunofluorescence (IF), cell viability assay and quantitative real-time (qRT)-PCR in tumor tissues. RESULTS: Combining anti-PD-1 antibodies with a STX-0119 failed to show a growth delay or survival benefit compared to each agent alone or control in any of the HCC models. Interestingly, evaluation of intratumoral CD8+ T cell infiltration by IF showed a significant increase after one-week treatment with STX-0119 (p=0.034). However, STX-0119 treatment simultaneously promoted increased immunosuppression in the tumor microenvironment by increasing the proportion of Tregs, tissue hypoxia and α-SMA activated cancer-associated fibroblasts (CAFs) measured by IF. Consistent with these findings, we found increased immature tumor vessels by IF and VEGF, Tgf-β and Vash2 expression by qPCR. CONCLUSION: Pharmacologic STAT3 inhibition could significantly enhance CD8+ T cell infiltration in HCC but also significantly alter the immunosuppression and vascular abnormalization in the tumor microenvironment.

PURPOSE: Metformin has been reported to be associated with improved cancer prognosis when used in combination with chemotherapy and/or radiotherapy. In this study, we present a systematic review and meta-analyses of studies evaluating the association of tumor pathological response with the use of metformin during neoadjuvant chemoradiotherapy (NACRT) in rectal and esophageal/gastroesophageal cancer patients. METHODS: We systematically searched databases for articles that compared concurrent metformin use with no metformin use in cancer patients treated with NACRT following the PRISMA 2020. The design and quality of the collected studies were reviewed, and meta-analyses were performed on the pathologic complete response (pCR) rate, tumor regression grade (TRG), T factor downstaging, and N factor downstaging. RESULTS: Three databases were searched, and 220 papers were screened. Five retrospective cohort study papers were eligible for the meta-analysis, with a total of 2041 patients. The included papers contained only rectal and esophageal/gastroesophageal cancers. In the metformin group, the pCR rate was 26% [20-32%], and metformin was associated with the pCR rate (odds ratio [OR] = 0.51 [0.34-0.76], p < 0.01). Meta-regression analysis of the pCR rate showed a positive correlation with adenocarcinoma (coefficient = 0.13 [0.02-0.25], p = 0.03) and fluoropyrimidine anticancer drug use (coefficient = 0.01 [0.001-0.02], p = 0.03). CONCLUSIONS: The results suggest that metformin is associated with pCR rate when used in combination with NACRT. The association of metformin and pCR rate in combination with fluoropyrimidine anticancer drugs was observed mostly for adenocarcinoma patients.

Aim: To evaluate the significance of next-generation sequencing-based gene panel testing in surgically resectable colorectal cancer by analyzing real-world data. Materials & methods: A total of 107 colorectal cancer patients who underwent curative surgery were included, and correlations between next-generation sequencing data and clinicopathological findings were evaluated. Results: More combination patterns in gene alteration were identified in advanced-stage tumors than in early-stage tumors. The copy number alteration count was significantly lower in right-sided colon tumors and early-stage tumors. Homologous recombination deficiency was more often identified in advanced-stage tumors, and high homologous recombination deficiency status was useful for identifying high-risk stage II tumors. Conclusion: Homologous recombination deficiency was identified as a useful result of gene panel testing with novel utility in clinical practice.

Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-cancer effects in many cancers, including colorectal cancer. However, the underlying molecular mechanisms of colorectal cancer metastasis remain unclear. Colorectal cancer cell lines were treated with metformin, and cell proliferation, invasion, and migration were analyzed in vitro. The relationship between metformin and the AMPK-mTOR axis was assessed by Western blot analysis and transfection with small interfering RNA. A colorectal cancer xenograft mouse model was used to observe the effects of metformin on liver metastasis. Immunohistochemical analysis was performed on liver metastatic tumors. In in vitro experiments, metformin significantly inhibited the proliferation, migration, and invasion only in HCT116 and SW837 cells, but not in HCT8 and Lovo cells. Only in HCT116 and SW837, a change in AMPK-mTOR expression was observed in a dose-dependent manner. In colorectal cancer xenograft mice, the liver metastatic rate (10% vs. 50%, p = 0.05) and the number of liver metastatic nodules (0.1/body vs. 1.2/body, p = 0.04) were significantly lower in the metformin group. Tumor proliferation and EMT were decreased and apoptosis was promoted only in metastatic liver tumors of mice treated with metformin. The molecular mechanism of the anti-cancer effects of metformin involves repression of mTOR pathways via AMPK activation. Moreover, the differences in metformin sensitivity depend on the response of the AMPK-mTOR pathway to metformin. Our study provides a theoretical basis for the anti-metastatic treatment of colorectal cancer using metformin.