Questionnaire to Survey Cosmetic Outcomes in Laparoscopic Surgery for Colorectal Cancer.

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.

ctDNA-based molecular residual disease and survival in resectable colorectal cancer.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.

Hybrid Abdominal Robotic Approach Using the hinotori™ Surgical Robot System with Transanal Total Mesorectal Excision for Rectal Cancer: The First Ever Case Report for Rectal Cancer.

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.

MUC1-C regulates NEAT1 lncRNA expression and paraspeckle formation in cancer progression.

The MUC1 gene evolved in mammals for adaptation of barrier tissues in response to infections and damage. Paraspeckles are nuclear bodies formed on the NEAT1 lncRNA in response to loss of homeostasis. There is no known intersection of MUC1 with NEAT1 or paraspeckles. Here, we demonstrate that the MUC1-C subunit plays an essential role in regulating NEAT1 expression. MUC1-C activates the NEAT1 gene with induction of the NEAT1_1 and NEAT1_2 isoforms by NF-κB- and MYC-mediated mechanisms. MUC1-C/MYC signaling also induces expression of the SFPQ, NONO and FUS RNA binding proteins (RBPs) that associate with NEAT1_2 and are necessary for paraspeckle formation. MUC1-C integrates activation of NEAT1 and RBP-encoding genes by recruiting the PBAF chromatin remodeling complex and increasing chromatin accessibility of their respective regulatory regions. We further demonstrate that MUC1-C and NEAT1 form an auto-inductive pathway that drives common sets of genes conferring responses to inflammation and loss of homeostasis. Of functional significance, we find that the MUC1-C/NEAT1 pathway is of importance for the cancer stem cell (CSC) state and anti-cancer drug resistance. These findings identify a previously unrecognized role for MUC1-C in the regulation of NEAT1, RBPs, and paraspeckles that has been co-opted in promoting cancer progression.

Cylindrical abdominoperineal resection for rectal cancer using the Hugo RAS system: The first ever case report for rectal cancer.

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.

A first report of right-hemicolectomy for ascending colon cancer in Japan with the da Vinci SP surgical robot system.

BACKGROUND: The da Vinci SP robotic surgical system received regulatory approval for use in colorectal cancer surgery in Japan in April 2023. Given the advantages of the precision of a robot and the postoperative cosmesis of single-site surgery, the system is expected to be further utilized for minimally invasive surgeries, in addition to the curative and safety-assured laparoscopic technique. CASE PRESENTATION: A 73-year-old man presented at our hospital with positive fecal occult blood. He was diagnosed with cT2N0M0 (Stage I) ascending colon cancer and underwent a right hemicolectomy, which was performed with the da Vinci SP system. The operation was performed safely, and the patient was discharged without complications. Pathology findings showed that complete mesocolic excision was achieved. CONCLUSIONS: Herein, we report the first colorectal cancer surgery performed using the da Vinci SP system in Japan. The use of this robotic surgical system with access forms for right hemicolectomy is safe and oncologically appropriate.

Tele-proctoring for minimally invasive surgery across Japan: An initial step toward a new approach to improving the disparity of surgical care and supporting surgical education.

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.

CD8-positive T Cell Infiltration With Human Leukocyte Antigen Class 1 Expression Predicts Patients With Stage IV Colorectal Cancer Survival.

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 (CD8Hi) and CD8 low (CD8Low) groups according to median CD8 expression. HLA class 1 (HLA1) expression was also evaluated using IHC staining and the cases were divided into HLA1Hi group and HLA1Low group according to 50% of HLA1 expression rate. CD8×HLA1 score was defined by the combination of CD8 and HLA1 expressions. RESULTS: CD8Hi and HLA1Hi cases were associated with better prognosis compared with CD8Low and HLA1Low 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×HLA1Hi cases predicted patient prognosis better than CD8×HLA1Int and CD8×HLA1Low 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.

World-first report of low anterior resection for rectal cancer with the hinotori™ Surgical Robot System: a case report.

BACKGROUND: The hinotori™ Surgical Robot System was approved for use in colorectal cancer surgery in Japan in 2022. This robot has advantages, such as an operation arm with eight axes, an adjustable arm base, and a flexible three-dimensional viewer, and is expected to be utilized in rectal cancer surgery. Herein, we report the world's first surgery for rectal cancer using the hinotori™ Surgical Robot System. CASE PRESENTATION: A 71-year-old woman presented to our hospital with bloody stools. A colonoscopy revealed type 2 advanced cancer in the rectum, and a histological examination exposed a well-differentiated adenocarcinoma. Abdominal enhanced computed tomography divulged rectal wall thickening without significant swelling of the lymph nodes or distant metastasis. Pelvic magnetic resonance imaging showed tumor invasion beyond the intrinsic rectal muscle layer. The patient was diagnosed with cStage IIa (cT3N0M0) rectal cancer and underwent low anterior resection using the hinotori™ Surgical Robot System. Based on an adequate simulation, surgery was safely performed with appropriate port placement and arm base-angle adjustment. The operating time was 262 min, with a cockpit time of 134 min. Subsequently, the patient was discharged 10 days postoperatively without complications. The pathological diagnosis was pStage IIA (cT3N0M0) and the circumferential resection margin was 6 mm. CONCLUSIONS: We report the first case of low anterior resection for rectal cancer using the hinotori™ Surgical Robot System, in which a safe and appropriate oncological surgery was performed.

Right hemicolectomy for ascending colon cancer using the hinotori surgical robot system: The first ever case report for colon cancer.

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.

[A Case of Sister Mary Joseph's Nodule after Radiation Therapy for Cervical Cancer].

An umbilical metastasis from an internal malignancy is called Sister Mary Joseph's nodule(SMJN)and has a poor prognosis. Herein, we report a case of umbilical metastasis of cervical cancer. A woman in her eighties underwent radiation therapy for cervical cancer(cT3bN0M0, cStage ⅢB). Primary tumor shrank after treatment, suggesting that radiation therapy induced complete response. Two years and 9 months after treatment, the patient presented with umbilical pain. A CT scan showed an umbilical mass near the umbilical hernia. PET-CT demonstrated high accumulation of FDG at the mass, which led to suspicion of umbilical metastasis(SMJN). Although she underwent radical surgery, she died from cancer 8 months after surgery.

The Relationship between LRP6 and Wnt/ß-Catenin Pathway in Colorectal and Esophageal Cancer.

High expression of low-density lipoprotein receptor-related protein 6 (LRP6), a key component of the Wnt/ß-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/ß-catenin pathway mutations. On immunohistochemical staining, high LRP6 expression was noted in three of 68 cases (4.4%), and high ß-catenin in 38 of 67 cases (56.7%) of CRC. High LRP6 expression was found in 21 of 82 cases (25.6%), and high ß-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.

Essential updates 2020/2021: Advancing precision medicine for comprehensive rectal cancer treatment.

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.

[A Case of Conversion Surgery after Long-Term Chemotherapy for Pancreatic Cancer with Peritoneal Metastasis].

A 66-year-old woman was referred to the gastroenterology division of our hospital due to elevation of serum CEA level. Contrast-enhanced CT showed a hypovascular tumor at the body of pancreas. She was diagnosed with pancreatic cancer by EUS-FNA. By laparotomy, we found white nodules on mesentery and abdominal wall, which were diagnosed as peritoneal metastasis. After systemic chemotherapy with 9 courses of gemcitabine(GEM)plus nab-paclitaxel(PTX)and 30 courses of mFOLFIRINOX, the tumor had shrunk and serum CA19-9 level were remarkably decreased. Distal pancreatectomy was performed as conversion surgery. Pathological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. S-1 was started as adjuvant chemotherapy, and she remains alive without recurrence 8 months after surgery.

Development of an ultralow-latency communication system using shared internet access: promoting the implementation of telemedicine.

Telemedicine is becoming increasingly important to address the shortage of gastrointestinal surgeons and disparities in domestic and international treatment outcomes for patients with colorectal cancer. The development of a low-latency communication system using existing communication infrastructure (shared internet access: SIA) is necessary to promote the use of telemedicine. The aim of this study was to develop a low-latency communication system using SIA. We conducted an experiment between Sapporo and Tokyo using an ultralow-latency communication system for remote medical education (TELEPRO®). The latency was measured using 2000 annotations from a monitor in Sapporo, which confirmed a median latency of 27.5 ms. A low-latency communication system based on SIA with latency lower than the maximum allowable latency for telemedicine was developed successfully.

Impact of the COVID-19 pandemic on colorectal cancer surgery in Japan: Clinical Study Group of Osaka University-A multicenter retrospective study.

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.

A case of infectious heterotopic ossification in the appendectomy scar, which formed an inflammatory granuloma.

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.

Postoperative pain management after concomitant sacrectomy for locally recurrent rectal cancer.

PURPOSE: To assess pain management in patients post-sacrectomy, focusing on opioid use, and to identify the factors associated with postoperative pain. METHODS: Patients who underwent resection of locally recurrent rectal cancer (LRRC) with concomitant sacrectomy at one of two hospitals between 2007 and 2020 were reviewed retrospectively. We examined the use of opioids preoperatively and postoperatively. Patients were classified into high and low sacrectomy groups based on the sacral bone resection level passing through the S3 vertebra. RESULTS: Sixty-four patients were enrolled. Opioid use was significantly higher in the high sacrectomy group than in the low sacrectomy group at all times assessed: on postoperative days 7, 14, 30, 90, 180, and 365. Opioid use 3 months after locally recurrent rectal cancer surgery was significantly higher in patients with local re-recurrence of the tumor than in those without re-recurrence (p < 0.05), and the median morphine-equivalent opioid use 3 months postoperatively was significantly higher in the high sacrectomy group (30 vs. 0 mg/day; p < 0.05). CONCLUSIONS: Opioid use after concomitant sacrectomy for LRRC was higher in the high sacrectomy group. Prolonged postoperative pain or increasing pain was associated with local recurrence.

[A Case of Palliative Abdominoperineal Resection and Perineal Reconstruction by Gluteus Maximus Flap following Regrowth of Primary Anal Canal Cancer with the Perianal Skin Infiltration after CRT].

An 85-year-old woman who visited the hospital with sores on the perianal skin was diagnosed with squamous cell carcinoma of the anal canal(cT3N1aM0, cStage ⅢC). She received chemoradiotherapy(radiation total 54 Gy/30 Fr, mitomycin C/capecitabine). The tumor initially shrank, but regrowth of the primary lesion, extensive perianal skin infiltration, and the appearance of para aortic lymph node metastases was observed 6 months later. Laparoscopic abdominoperineal resection was performed to mitigate strong local symptoms. The perineal defect was repaired with bilateral gluteus maximus flap(V- Y flap). The operation prevented anal pain and improved ADL. The patient is currently undergoing chemotherapy 7 months after surgery. We report the case with a review of the literature in which ADL was improved by salvage surgery for tumor regrowth with severe local symptoms and distant metastases after chemoradiotherapy for squamous cell carcinoma of the anal canal.

Colorectal Surgery in the COVID-19 Pandemic Era.

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.