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Background This study aimed to evaluate the influence of anesthetic management with propofol or sevoflurane on the prognosis of patients undergoing gynecologic cancer surgery. Methods This retrospective cohort study included patients who underwent gynecologic cancer (cervical, endometrial, and ovarian cancer) surgery between 2006 and 2018 at the National Hospital Organization Osaka National Hospital. Patients were grouped according to anesthesia type for maintenance of anesthesia: propofol or sevoflurane. After propensity score matching, Kaplan-Meier survival curves were constructed for overall survival, cancer-specific survival, and recurrence-free survival. Univariate and multivariate cox regression models were used to compare hazard ratios for recurrence-free survival. Results A total of 193 patients with propofol and 94 with sevoflurane anesthesia were eligible for analysis. After propensity score matching, 94 patients remained in each group. The sevoflurane group showed significantly lower survival rates than the propofol group with respect to 10-year overall survival (89.3% vs. 71.6%; p = 0.007), 10-year cancer-specific survival (91.0% vs 80.2%; p = 0.039), and 10-year recurrence-free survival (85.6% vs. 67.7%; p = 0.008). Sevoflurane anesthesia was identified as an independent risk factor for recurrence-free survival. Furthermore, distant recurrence was significantly more frequent in the sevoflurane group than in the propofol group (p < 0.001). Conclusion In patients undergoing gynecologic cancer surgery, sevoflurane anesthesia was associated with worse overall, cancer-specific, and recurrence-free survival than propofol anesthesia., Author(s): Eriko Takeyama [sup.1], Masaaki Miyo [sup.2], Hisanori Matsumoto [sup.3], Kenji Tatsumi [sup.3], Eizo Amano [sup.1], Motohiro Hirao [sup.2], Hiromi Shibuya [sup.1] Author Affiliations: (1) grid.416803.8, 0000 0004 0377 7966, [...]

In May 2023, the Hugo RAS system obtained pharmaceutical approval for use in gastroenterological surgery in Japan. It is expected to be particularly effective in rectal cancer surgery, which require the manipulation of the deep pelvic cavity and communication with surgeons operating from the intraperitoneal and anal approaches. A 68‐year‐old woman presented to our hospital with bloody stools and was diagnosed with cStage I (cT2N0M0) rectal cancer and underwent abdominoperineal resection employing the Hugo RAS system. Two arm carts were placed on the left and right lateral sides with an interleg space, and trocars were placed in a straight line between the right superior iliac spine and umbilicus. Herein, we report the first abdominoperineal resection for rectal cancer using the Hugo RAS system. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to verify the clinical feasibility of tele‐proctoring using our ultra‐low latency communication system with shared internet access. Methods: Connections between two multiple remote locations at various distances were established through the TELEPRO® tele‐proctoring system. The server records the latency between the two locations for tele‐proctoring using the annotations. Questionnaires were administered to the surgeons, assistants, and medical staff. Respondents rated the quickness and quality of communication in terms of latency and disturbances in the audio, video, and usefulness of the live telestrations with annotation. Results: Seven hospitals tele‐proctored with Sapporo Medical University between January 2021 and September 2022. The median latency of annotation between the two locations ranged from 24.5 to 48.5 ms. No major technological problems occurred, such as streaming interruption, loss of video or audio, poor resolution. The video encoding time was 10 ms, and its decoding time was 0.8 ms. The total latency positively correlated with the distance between two locations (R = 0.55, p < 0.01). The quality of communication regarding latency, disturbance, and surgical education with intraoperative annotative instructions showed similar trends, with perfectly fine being the most common response. No significant differences in surgical quality, educational effect, or social impact were observed between the latency ≥30 and <30 ms groups for whether the size of latency affects surgical education. Conclusion: The feasibility of the tele‐proctoring system is expected to be a sustainable approach to help education for young surgeons and surgical supports in rural areas, thereby reducing disparities in health care. [ABSTRACT FROM AUTHOR]

The hinotori Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022 in Japan, and its advantages, including its operating arm with eight axes, adjustable arm base, and flexible 3D viewer, are expected to be utilized in colon cancer surgery. A 68‐year‐old woman presented to our hospital with abdominal pain and was diagnosed with cStageIIa (cT3N0M0) ascending colon cancer and underwent right hemicolectomy using the hinotori Surgical Robot System with the appropriate port placement on the arc around the hepatic flexure, which was available for both ileocecal manipulation and lymph node dissection, and adjustment of the angle of the arm base to further reduce interference. Herein we report the world's first surgery for colorectal cancer using the hinotori Surgical Robot System. [ABSTRACT FROM AUTHOR]

Aims: Risk‐scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. Methods: In this multi‐institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19–9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1–10), and high risk (score ≥11). Overall and recurrence‐free survival curves were calculated using the Kaplan–Meier method. After propensity‐score matching in the intermediate‐risk group, we compared clinicopathological features and outcomes. Results: There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low‐, intermediate‐, and high‐risk groups, respectively. Intermediate‐risk group patients who received neoadjuvant chemotherapy had significantly better recurrence‐free survival than that of patients without neoadjuvant chemotherapy (P =.0453). After propensity‐score matching in the intermediate‐risk group, the recurrence‐free survival rate was better in patients who received neoadjuvant chemotherapy (P =.0261). But the overall survival rate was not improved after the matching. Conclusion: Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence‐free survival period for intermediate‐risk patients with preoperative risk scores in the range of 1–10, but the overall survival was not improved by neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

High expression of low-density lipoprotein receptor-related protein 6 (LRP6), a key component of the Wnt/β-catenin signaling pathway, is reported to be associated with malignant potential in some solid tumors including breast cancer and hepatocellular carcinoma. Few reports, however, have examined its function and clinical significance in colorectal cancers (CRC) demonstrating constitutive activation of Wnt signaling. Here, we compared the expression level and function of LRP6 in CRC with that of esophageal squamous cell carcinoma (ESCC) bearing few Wnt/β-catenin pathway mutations. On immunohistochemical staining, high LRP6 expression was noted in three of 68 cases (4.4%), and high β-catenin in 38 of 67 cases (56.7%) of CRC. High LRP6 expression was found in 21 of 82 cases (25.6%), and high β-catenin expression in 29 of 73 cases (39.7%) of ESCC. In our in vitro studies, LRP6 knockdown hardly changed Wnt signaling activity in CRC cell lines with mutations in Wnt signaling downstream genes. In contrast, in ESCC cell lines without Wnt signaling-related mutations, LRP6 knockdown significantly decreased Wnt signaling activity. LRP6 function may depend on constitutive activation of Wnt signaling. [ABSTRACT FROM AUTHOR]

In the paradigm shift related to rectal cancer treatment, we have to understand a variety of new emerging topics to provide appropriate treatment for individual patients as precision medicine. However, information on surgery, genomic medicine, and pharmacotherapy is highly specialized and subdivided, creating a barrier to achieving thorough knowledge. In this review, we summarize the perspective for rectal cancer treatment and management from the current standard‐of‐care to the latest findings to help optimize treatment strategy. [ABSTRACT FROM AUTHOR]

Aim: Due to the overwhelming spread of SARS‐CoV‐2 and its disruption of the healthcare system, delays and reduced numbers were reported for colorectal cancer screening, colonoscopies, and surgery during the COVID‐19 pandemic. This multicenter retrospective study investigated the still poorly understood impact of the COVID‐19 pandemic on colorectal cancer treatment in Japan. Methods: This study was organized by the Clinical Study Group of Osaka University, which comprised 32 major institutions in Osaka. We retrospectively analyzed the number of surgeries and colonoscopies performed and the characteristics of patients who underwent surgery for colorectal cancer between March 2019 and February 2021. We compared data collected before and during the COVID‐19 pandemic. We also assessed the methods used for detecting colorectal cancer, including fecal occult blood test, abdominal symptoms, and anemia. Results: The COVID‐19 pandemic caused reductions in the annual numbers of surgeries (3569 vs 3198) and colonoscopies (67 622 vs 58 183) performed in the 2020 fiscal year, compared to the 2019 fiscal year. During the COVID‐19 pandemic, a significantly lower proportion of patients were treated for clinical stages ≤I (24.2% vs 26.9%; P =.011), compared to the proportion treated before the pandemic. Fecal occult blood tests for detecting colorectal cancer were used significantly less frequently during the COVID‐19 pandemic (26.2% vs 29.6%; P =.002). These trends were more significant in larger institutions. Conclusion: The COVID‐19 pandemic reduced the number of colonoscopies and surgeries performed for colorectal cancer and hindered the detection of asymptomatic early‐stage cancers, and its impact varied by hospital size. [ABSTRACT FROM AUTHOR]

Inflammatory granulomas often develop in surgical scars due to the presence of foreign bodies, such as sutures. These granulomas are called Schloffer's tumors. Here, we report a case of heterotopic ossification(HO) in an appendectomy scar that formed an inflammatory granuloma following HO infection. A 90-year-old woman was referred to our hospital with a chief complaint of a painful mass in the right lower quadrant of her abdomen. She had a history of acute appendicitis, for which she underwent an appendectomy approximately 70 years previously. Imaging studies demonstrated a tumor containing a linear-shaped agent located in the abdominal wall under the surgical scar where the appendectomy was performed. She was then diagnosed with Schloffer's tumor, for which she underwent surgical resection. However, histopathological examination revealed that the tumor was a fibrous connective tissue mass with a lamellar bone inside. [ABSTRACT FROM AUTHOR]

According to the current international guidelines, high‐risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE‐Japan project includes a large‐scale patient‐screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE‐Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients. [ABSTRACT FROM AUTHOR]

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full‐thickness partial resection using a hybrid approach of laparoscopic surgery and single‐incision intragastric surgery (SIIGS). A 69‐year‐old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall‐inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall‐inversion surgery by removing size limitations. [ABSTRACT FROM AUTHOR]

Recently, v-raf murine sarcoma viral oncogene homologue B (BRAF) fusions have been identified in multiple cancer types using comprehensive genomic profiling (CGP) assays. BRAF fusions are extremely rare, occurring in <0.5% of patients with metastatic colorectal cancer (mCRC). Until now, there is no standard treatment for mCRC with BRAF fusions. Here, we report a recurrent colorectal cancer case that harbored an EXOC4-BRAF fusion. A 40-year-old female patient with a 2-year history of type 2 diabetes was diagnosed with pathologically confirmed stage IV rectal adenocarcinoma with liver metastasis. She underwent R0 resection after neoadjuvant therapy; however, her disease recurred at multiple metastatic sites (lymph nodes, ovary, and peritoneal gland). A rectal cancer surgical specimen was submitted for CGP (Foundation One) to identify potential targets to develop treatment strategies. An EXOC4-BRAF fusion was identified, and she achieved partial response to FOLFOX + panitumumab which is a fully human antibody directed against epidermal growth factor receptor. No EXOC4-BRAF fusions in colorectal cancer cases have been reported to date. Further studies investigating molecular mechanisms and novel targeted therapy approaches are required. [ABSTRACT FROM AUTHOR]

Aim: In response to the rising use of laparoscopic surgery, recent studies have shown that laparoscopic multivisceral resections for locally advanced colon cancer are safe, feasible, and provide acceptable oncological outcomes. However, the usefulness of laparoscopic multivisceral resection remains controversial. Here, we aimed to compare short‐term and long‐term outcomes between laparoscopic and open multivisceral resection approaches for treating locally advanced colon cancer. Methods: We retrospectively collected data on 1315 consecutive patients admitted to the National Hospital Organization, Osaka National Hospital, for surgical treatment of colorectal cancer between 2010 and 2017. We assessed invasiveness in terms of operating times, blood loss, and complications. Oncological outcomes included 5‐year survival rates and recurrences. Results: We included 85 patients that underwent a colectomy with a multivisceral resection for locally advanced colon cancer; of these, 38 were treated with a laparoscopic approach and 47 were treated with an open approach. Compared to the open surgery group, the laparoscopic group had significantly less blood loss (median volume: 25 vs 140 mL, P <0.001), a lower complication rate (10.5% vs 29.8%, P = 0.036), and shorter hospital stays (12 vs 15 days, P = 0.028). After excluding patients with stage Ⅳ colon cancer, the groups showed similar pathologic outcomes and no significant differences in 5‐year disease‐free survival (73.9% vs 67.4%; P = 0.664) or 5‐year overall survival (75.8% vs 67.7%; P = 0.695). Conclusion: A laparoscopic approach for locally advanced colon cancer could be less invasive than an open approach without affecting oncological outcomes in selected patients. [ABSTRACT FROM AUTHOR]

Aim: Single‐site laparoscopic interval appendectomy (SLIA) for severe complicated appendicitis after conservative treatment (CT) to ameliorate inflammation and eradicate the abscess should be safer and less invasive than emergency appendectomy (EA). However, only a few reports have been published regarding SLIA. Methods: We retrospectively collected data on 264 consecutive patients admitted to Kinan Hospital for treatment of appendicitis between 2012 and 2018. The safety and feasibility of SLIA and its perioperative outcomes for severe complicated appendicitis were investigated. Results: A total of 61 patients were included in this study, 25 of whom underwent CT and 36 EA. Among the 25 patients who underwent CT, 23 (92.0%) succeeded; a total of 16 patients (69.5%) underwent SLIA. Compared to the EA group, the SLIA group had less bleeding (median volume 8.5 vs 50 mL, P = .005) and lower rate of expansion surgery (0% vs 27.8%, P = .022). Although the postoperative hospital stay was shorter in the SLIA group than in the EA group (9 vs 12 days, P = .008), the total hospital stay, including the CT period, was longer in the SLIA group than in the EA group (24 vs 12 days, P < .001). Conclusion: SLIA is safe, feasible, and less invasive than EA and may provide the advantages of minimally invasive surgery even if appendicitis is severe. SLIA may be a promising option for complicated appendicitis in select cases despite its disadvantage of prolonging the hospital stay. [ABSTRACT FROM AUTHOR]

BMI1 is a component of the PRC1 complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells. In addition, we show that MUC1-C blocks miR-200c-mediated downregulation of BMI1 expression. The functional significance of this MUC1-C→BMI1 pathway is supported by the demonstration that targeting MUC1-C suppresses BMI1-induced ubiquitylation of H2A and thereby derepresses homeobox HOXC5 and HOXC13 gene expression. Notably, our results further show that MUC1-C binds directly to BMI1 and promotes occupancy of BMI1 on the CDKN2A promoter. In concert with BMI1-induced repression of the p16INK4a tumor suppressor, we found that targeting MUC1-C is associated with induction of p16INK4a expression. In support of these results, analysis of three gene expresssion datasets demonstrated highly significant correlations between MUC1-C and BMI1 in breast cancers. These findings uncover a previously unrecognized role for MUC1-C in driving BMI1 expression and in directly interacting with this stem cell factor, linking MUC1-C with function of the PRC1 in epigenetic gene silencing.

Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. Furthermore, we identified pivotal roles of GLUD1 and SLC25A13 in nutritional stress. GLUD1 and SLC25A13 were associated with tumor aggressiveness and poorer prognosis of colorectal cancer. In conclusion, GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments. [ABSTRACT FROM AUTHOR]

In Japan, pharmaceutical approval for the use of the da Vinci SP (dV SP) Surgical System in colorectal cancer surgery was obtained in September 2022. This system has an operating arm with three instruments and one scope to be manipulated through a single incision in colorectal cancer surgery. An 88-year-old female presented to our hospital with melena and was diagnosed with cStage IIa descending colon cancer (cT3N0M0). The patient underwent left hemicolectomy with the dV SP using an Access Port kit. The Access Port kit was inserted into a 3-cm vertical skin incision at the umbilicus. With only this surgical wound, mobilization from the rectum to the colon, and lymph node dissection were performed. Herein, we report the world's first descending colon cancer resection with the dV SP using an Access Port kit., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

In Japan, the hinotori™ Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022. This system has an operating arm with eight axes, adjustable arm base, and flexible three-dimensional viewer, which are expected to be advantageous in colorectal cancer surgery. A 55-year-old man presented to our hospital with melena and was diagnosed with cStage IIA (cT3N0M0) rectal cancer. The patient underwent intersphincteric resection using hinotori™ Surgical Robot System. Appropriate port placement was available for rectal manipulation, lymph node dissection, and arm base angle adjustment. Herein, we report the world's first rectal cancer surgery using the hinotori™ Surgical Robot System with TaTME by two teams., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Background and Objectives: There has been a steady increase in the use of minimally invasive surgery, including conventional multiport laparoscopic surgery (MLS) and single-site laparoscopic surgery (SLS) for colorectal cancer. We aimed to evaluate how important the cosmetic outcome, one of the advantages of SLS, is to patients and whether SLS reflects social needs., Methods: We used a web-based questionnaire to survey nonmedical and medical workers for what factors were considered on the assumption that respondents undergo colorectal cancer surgery and that the most important person for them undergoes. Five items (curability, safety, pain, length of hospital stay, and cosmetic outcomes) were compared. After paired photographs before and after SLS and MLS were shown, perceptions of body image and cosmesis were assessed using a visual analog scale., Results: This study included a total of 1352 respondents (990 nonmedical and 362 medical). Curability had the highest score (49.9-53.7 points), followed by safety (23.8-24.7 points). The scores for cosmetic outcomes (6.2-7.1 points) were almost equal to those of the length of hospital stay (6.2-7.1 points), which was associated with medical costs and pain (10.0-11.1 points), one of the main reasons for fear of surgery. Participants who were female, younger, and in the nonmedical group placed great importance on cosmetic outcomes. For all questions regarding body image and cosmesis, SLS had superior scores compared with MLS., Conclusions: Understandably, curability, and safety were most important in colorectal cancer surgery. However, medical workers should consider cosmetic outcomes, even in malignant cases., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aim: The immune microenvironment in cancer correlates with cancer progression and patient prognosis. Cancer immune microenvironment evaluation, based on CD3 + and CD8 + T cell infiltration at the center and invasive margin of the tumor, is defined as the immunoscore. An international multicenter analysis revealed that the immunoscore can accurately predict the prognosis of patients with colorectal cancer (CRC) (stage I, II, and III). However, no markers are currently available to predict the prognosis in patients with stage IV CRC. We thus aimed to analyze the immune microenvironment in patients with stage IV CRC in this study., Patients and Methods: We analyzed the immune microenvironment of patients with stage IV CRC using immunohistochemical (IHC) staining. We evaluated the expressions of CD8 and the cases were divided into CD8 high (CD8 Hi ) and CD8 low (CD8 Low ) groups according to median CD8 expression. HLA class 1 (HLA1) expression was also evaluated using IHC staining and the cases were divided into HLA1 Hi group and HLA1 Low group according to 50% of HLA1 expression rate. CD8×HLA1 score was defined by the combination of CD8 and HLA1 expressions., Results: CD8 Hi and HLA1 Hi cases were associated with better prognosis compared with CD8 Low and HLA1 Low cases according to a log-rank test, respectively. We defined a novel biomarker by combining CD8 + T-cell infiltration and HLA1 expression, referred to as the CD8×HLA1 score. We found that CD8×HLA1 Hi cases predicted patient prognosis better than CD8×HLA1 Int and CD8×HLA1 Low according to a log-rank test., Conclusion: The combination of CD8 + T cell infiltration and HLA1 expression is crucial for cancer immune microenvironment evaluation in CRCs., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The aim of this study was to verify the clinical feasibility of tele-proctoring using our ultra-low latency communication system with shared internet access., Methods: Connections between two multiple remote locations at various distances were established through the TELEPRO® tele-proctoring system. The server records the latency between the two locations for tele-proctoring using the annotations. Questionnaires were administered to the surgeons, assistants, and medical staff. Respondents rated the quickness and quality of communication in terms of latency and disturbances in the audio, video, and usefulness of the live telestrations with annotation., Results: Seven hospitals tele-proctored with Sapporo Medical University between January 2021 and September 2022. The median latency of annotation between the two locations ranged from 24.5 to 48.5 ms. No major technological problems occurred, such as streaming interruption, loss of video or audio, poor resolution. The video encoding time was 10 ms, and its decoding time was 0.8 ms. The total latency positively correlated with the distance between two locations ( R  = 0.55, p  < 0.01). The quality of communication regarding latency, disturbance, and surgical education with intraoperative annotative instructions showed similar trends, with perfectly fine being the most common response. No significant differences in surgical quality, educational effect, or social impact were observed between the latency ≥30 and <30 ms groups for whether the size of latency affects surgical education., Conclusion: The feasibility of the tele-proctoring system is expected to be a sustainable approach to help education for young surgeons and surgical supports in rural areas, thereby reducing disparities in health care., Competing Interests: Eiji Oki, Susumu Eguchi, Daisuke Ichikawa, Yuko Kitagawa, Masaki Mori, and Ichiro Takemasa are members of the Editorial Board of Annals of Gastroenterological Surgery., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

In the paradigm shift related to rectal cancer treatment, we have to understand a variety of new emerging topics to provide appropriate treatment for individual patients as precision medicine. However, information on surgery, genomic medicine, and pharmacotherapy is highly specialized and subdivided, creating a barrier to achieving thorough knowledge. In this review, we summarize the perspective for rectal cancer treatment and management from the current standard-of-care to the latest findings to help optimize treatment strategy., Competing Interests: The other authors declare no conflicts of interest. Ichiro Takemasa is the editorial member of the Annals of Gastroenterologial Surgery., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Aim: Due to the overwhelming spread of SARS-CoV-2 and its disruption of the healthcare system, delays and reduced numbers were reported for colorectal cancer screening, colonoscopies, and surgery during the COVID-19 pandemic. This multicenter retrospective study investigated the still poorly understood impact of the COVID-19 pandemic on colorectal cancer treatment in Japan., Methods: This study was organized by the Clinical Study Group of Osaka University, which comprised 32 major institutions in Osaka. We retrospectively analyzed the number of surgeries and colonoscopies performed and the characteristics of patients who underwent surgery for colorectal cancer between March 2019 and February 2021. We compared data collected before and during the COVID-19 pandemic. We also assessed the methods used for detecting colorectal cancer, including fecal occult blood test, abdominal symptoms, and anemia., Results: The COVID-19 pandemic caused reductions in the annual numbers of surgeries (3569 vs 3198) and colonoscopies (67 622 vs 58 183) performed in the 2020 fiscal year, compared to the 2019 fiscal year. During the COVID-19 pandemic, a significantly lower proportion of patients were treated for clinical stages ≤I (24.2% vs 26.9%; P  = .011), compared to the proportion treated before the pandemic. Fecal occult blood tests for detecting colorectal cancer were used significantly less frequently during the COVID-19 pandemic (26.2% vs 29.6%; P  = .002). These trends were more significant in larger institutions., Conclusion: The COVID-19 pandemic reduced the number of colonoscopies and surgeries performed for colorectal cancer and hindered the detection of asymptomatic early-stage cancers, and its impact varied by hospital size., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

The novel coronavirus disease 2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread at a very fast rate, overwhelming and disrupting healthcare systems around the world since its outbreak in December 2019 in China. As of October 2021, the total number of COVID-19 cases exceeds 240,000,000, and the total number of deaths is close to 5,000,000. In the situation of widespread SARS-CoV-2 infection, restrictions on the medical system due to shifts in medical care to accommodate the pandemic will occur, and its impact on surgical and endoscopic treatment for colorectal cancer is inevitable. Therefore, it is necessary to satisfy all of the following requirements: patient safety, prevention of exposure of healthcare workers including surgeons, prevention of nosocomial infection, and a decision on how to treat the primary disease. Surgical triage is also required, based on comprehensive consideration of the patient's condition, the severity of the disease, the SARS-CoV-2 infection situation in the region, and the medical supply system at each facility, including medical resources, human resources, and the availability of medical equipment. Understanding the diagnostic and treatment environment that the COVID-19 pandemic has dramatically changed is important in providing appropriate surgical care to patients who require surgery while taking utmost care to prevent the spread of COVID-19., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 by The Japan Society of Coloproctology.)

The NuRD chromatin remodeling and deacetylation complex, which includes MTA1, MBD3, CHD4, and HDAC1 among other components, is of importance for development and cancer progression. The oncogenic mucin 1 (MUC1) C-terminal subunit (MUC1-C) protein activates EZH2 and BMI1 in the epigenetic reprogramming of triple-negative breast cancer (TNBC). However, there is no known link between MUC1-C and chromatin remodeling complexes. Here, we showed that MUC1-C binds directly to the MYC HLH-LZ domain and identified a previously unrecognized MUC1-C→MYC pathway that regulates the NuRD complex. MUC1-C/MYC complexes selectively activated the MTA1 and MBD3 genes and posttranscriptionally induced CHD4 expression in basal- but not luminal-type BC cells. In turn, MUC1-C formed complexes with these NuRD components on the ESR1 promoter. Downregulating MUC1-C decreased MTA1/MBD3/CHD4/HDAC1 occupancy and increased H3K27 acetylation on the ESR1 promoter, with induction of ESR1 expression and downstream estrogen response pathways. Targeting MUC1-C and these NuRD components also induced expression of FOXA1, GATA3, and other markers associated with the luminal phenotype. These findings support a model in which MUC1-C activates the NuRD complex to drive dedifferentiation and reprogramming of TNBC cells. SIGNIFICANCE: MUC1-C directly interacts with MYC to activate the NuRD complex, mediating regulation of the estrogen receptor in triple-negative breast cancer cells., (©2019 American Association for Cancer Research.)

The oncogenic MUC1-C protein and the TWIST1 epithelial-mesenchymal transition transcription factor (EMT-TF) are aberrantly expressed in triple-negative breast cancer (TNBC) cells. However, there is no known association between MUC1-C and TWIST1 in TNBC or other cancer cells. Here, we show that MUC1-C activates STAT3, and that MUC1-C and pSTAT3 drive induction of the TWIST1 gene. In turn, MUC1-C binds directly to TWIST1, and MUC1-C/TWIST1 complexes activate MUC1-C expression in an autoinductive circuit. The functional significance of the MUC1-C/TWIST1 circuit is supported by the demonstration that this pathway is sufficient for driving (i) the EMT-TFs, ZEB1 and SNAIL, (ii) multiple genes in the EMT program as determined by RNA-seq, and (iii) the capacity for cell invasion. We also demonstrate that the MUC1-C/TWIST1 circuit drives (i) expression of the stem cell markers SOX2, BMI1, ALDH1, and CD44, (ii) self-renewal capacity, and (iii) tumorigenicity. In concert with these results, we show that MUC1-C and TWIST1 also drive EMT and stemness in association with acquired paclitaxel (PTX) resistance. Of potential therapeutic importance, targeting MUC1-C and thereby TWIST1 reverses the PTX refractory phenotype as evidenced by synergistic activity with PTX against drug-resistant cells. These findings uncover a master role for MUC1-C in driving the induction of TWIST1, EMT, stemness, and drug resistance, and support MUC1-C as a highly attractive target for inhibiting TNBC plasticity and progression., (©2019 American Association for Cancer Research.)

The oncogenic MUC1-C protein is overexpressed in triple-negative breast cancer (TNBC) cells and contributes to their epigenetic reprogramming and chemoresistance. Here we show that targeting MUC1-C genetically or pharmacologically with the GO-203 inhibitor, which blocks MUC1-C nuclear localization, induced DNA double-strand breaks and potentiated cisplatin (CDDP)-induced DNA damage and death. MUC1-C regulated nuclear localization of the polycomb group proteins BMI1 and EZH2, which formed complexes with PARP1 during the DNA damage response. Targeting MUC1-C downregulated BMI1-induced H2A ubiquitylation, EZH2-driven H3K27 trimethylation, and activation of PARP1. As a result, treatment with GO-203 synergistically sensitized both mutant and wild-type BRCA1 TNBC cells to the PARP inhibitor olaparib. These findings uncover a role for MUC1-C in the regulation of PARP1 and identify a therapeutic strategy for enhancing the effectiveness of PARP inhibitors against TNBC. SIGNIFICANCE: These findings demonstrate that targeting MUC1-C disrupts epigenetics of the PARP1 complex, inhibits PARP1 activity, and is synergistic with olaparib in TNBC cells., (©2019 American Association for Cancer Research.)

The immune checkpoint ligand PD-L1 and the transmembrane mucin MUC1 are upregulated in triple-negative breast cancer (TNBC), where they contribute to its aggressive pathogenesis. Here, we report that genetic or pharmacological targeting of the oncogenic MUC1 subunit MUC1-C is sufficient to suppress PD-L1 expression in TNBC cells. Mechanistic investigations showed that MUC1-C acted to elevate PD-L1 transcription by recruitment of MYC and NF-κB p65 to the PD-L1 promoter. In an immunocompetent model of TNBC in which Eo771/MUC1-C cells were engrafted into MUC1 transgenic mice, we showed that targeting MUC1-C associated with PD-L1 suppression, increases in tumor-infiltrating CD8 + T cells and tumor cell killing. MUC1 expression in TNBCs also correlated inversely with CD8, CD69, and GZMB, and downregulation of these markers associated with decreased survival. Taken together, our findings show how MUC1 contributes to immune escape in TNBC, and they offer a rationale to target MUC1-C as a novel immunotherapeutic approach for TNBC treatment. Significance: These findings show how upregulation of the transmembrane mucin MUC1 contributes to immune escape in an aggressive form of breast cancer, with potential implications for a novel immunotherapeutic approach. Cancer Res; 78(1); 205-15. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Complete mesocolic excision has been suggested to improve oncological outcomes for patients with colon cancer. However, the long-term outcomes of single-site laparoscopic colectomy with complete mesocolic excision remain unclear., Objective: We evaluated the long-term outcomes of single-site laparoscopic colectomy with complete mesocolic excision compared with conventional multiport laparoscopic colectomy for colon cancer, as well as the short-term outcomes., Design: This is a single-center, retrospective study., Settings: The study was conducted at Osaka University Hospital in Japan., Patients: A total of 971 consecutive patients who underwent laparoscopic surgery for colon cancer between 2008 and 2014 were included. Of these patients, 517 were analyzed using propensity score matching (231 with single-site laparoscopic colectomy and 286 with conventional multiport laparoscopic colectomy)., Main Outcome Measures: Recurrence, survival, intraoperative morbidity, and postoperative complications were analyzed., Results: Before propensity score matching, the single-site laparoscopic colectomy group had greater proportions of women and of patients with right-sided and early stage tumors compared with the conventional multiport laparoscopic colectomy group. After matching, the 2 groups each included 200 patients and did not significantly differ in any patient characteristics. The median follow-up period was 41.4 months. The 2 groups showed similar rates of intraoperative morbidity (p = 0.22) and postoperative complications (p = 0.87). Rates of 3-year disease-free and overall survival in single-site laparoscopic colectomy and conventional, multiport, laparoscopic colectomy groups were 95.5% and 91.3% (p = 0.44) and 100.0% and 98.7% (p = 0.24). The 3-year disease-free and overall survival rates in each stage did not significantly differ between the 2 groups., Limitations: This study was limited by its retrospective nature., Conclusions: Single-site laparoscopic colectomy with complete mesocolic excision for colon cancer provided acceptable perioperative outcomes and oncological outcomes, similar to those achieved with conventional multiport laparoscopic colectomy. Evidence accumulation from randomized controlled trials will be necessary to promote the wide acceptance of single-site laparoscopic colectomy. See Video Abstract at http://links.lww.com/DCR/A326.

Folate plays a pivotal role in the one-carbon metabolism needed for methylation reactions, nucleotide synthesis, and DNA repair. Although folate metabolism was recently shown to be associated with carcinogenesis in some solid tumors, the importance of folate metabolism in colorectal cancer remains unclear. In the present investigation we found that expression of three mitochondrial folate metabolic enzymes, serine hydroxymethyl transferase (SHMT2), methylenetetrahydrofolate dehydrogenase (MTHFD2) and aldehyde dehydrogenase 1 family member L2 (ALDH1L2), were upregulated in human colorectal tumor tissues compared to normal tissues. Colorectal cancer tissue samples were obtained from 117 consecutive patients. We evaluated the expression of the enzymes with immunohistochemical analysis and determined their relevance to clinicopathological characteristics and prognosis. Rates of recurrence-free survival (RFS) and overall survival (OS) in patients with high expression of SHMT2, MTHFD2 and ALDH1L2 tended to be lower than in patients with low expression of SHMT2, MTHFD2 and ALDH1L2 (P=0.446 and P=0.337, P=0.099 and P=0.064, P=0.178 and P=0.257, respectively). Notably, the combined high expression of SHMT2, MTHFD2 and ALDH1L2 (triple high) was more highly associated with poor prognosis than the individual expression levels (RFS; P=0.004 and OS; P=0.037). A multivariate analysis showed that triple high expression was independently associated with RFS (P=0.017). These findings suggested that mitochondrial folate metabolic enzymes could provide a potential therapeutic strategy for treating colorectal cancer.