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1.
Cancer Diagn Progn ; 4(3): 264-269, 2024.
Article in English | MEDLINE | ID: mdl-38707722

ABSTRACT

Background/Aim: Intestinal malrotation (IM) often remains undetected until adulthood, being discovered during testing or surgery for other comorbidities. Preoperative understanding of this anatomical abnormality is crucial. Case Report: An 80-year-old woman presented with cecal cancer. Three-dimensional computed tomography (CT) revealed that the cecum was located at the midline of the abdominal cavity, the duodenum did not cross the midline, and the ileocolic vein ran to the left. Clinically diagnosed with stage IVc cecal cancer complicated by IM, the patient underwent laparoscopic surgery. The ascending colon and cecum were not fixed to the retroperitoneum. The duodenum lacked the second, third, and fourth portions and the small bowel was distributed on the left and right sides of the abdominal cavity. Adhesions had shortened the mesentery, which were released close to their normal positions. Conclusion: Although laparoscopic surgery is superior to open surgery in terms of securing the field of view in a narrow space, providing a magnifying effect, and minimal invasiveness, it has a limited field of view and is inferior in terms of grasping the overall anatomy, which may be disadvantageous in cases of anatomical abnormalities. Colorectal cancer with IM is rare; however, the rate of preoperative diagnosis seems to be increasing thanks to improvements in diagnostic imaging, such as three-dimensional CT scans. In this study, we also reviewed 49 cases of colorectal cancer associated with IM.

2.
Surg Case Rep ; 10(1): 111, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700734

ABSTRACT

BACKGROUND: Pouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas. CASE PRESENTATION: First case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn's disease. SECOND CASE: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch-perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients. CONCLUSIONS: We encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient's quality of life and reintegration into society.

3.
Gan To Kagaku Ryoho ; 51(4): 463-465, 2024 Apr.
Article in Japanese | MEDLINE | ID: mdl-38644323

ABSTRACT

We reported a case of sigmoid colon cancer with horseshoe kidney. A 79-year-old man had lower abdominal pain and underwent colonoscopy. The results of colonoscopy revealed sigmoid cancer. Preoperative computed tomography revealed horseshoe kidney. He underwent radical laparoscopic surgery. The histopathological diagnosis was pStage Ⅱa(The 9th Edition). He has not recurred 22 months later after operation. Surgery for colorectal cancer with congenital anomalies of the urinary tract requires attention to intraoperative secondary injuries. Therefore, preoperative evaluation using 3D-CT is useful tool for safety. Operating the proper dissecting normal layer would make safe laparoscopic operation possible without unexpected injuries.


Subject(s)
Fused Kidney , Sigmoid Neoplasms , Humans , Male , Aged , Sigmoid Neoplasms/surgery , Sigmoid Neoplasms/pathology , Sigmoid Neoplasms/complications , Fused Kidney/complications , Fused Kidney/surgery , Tomography, X-Ray Computed , Laparoscopy , Colonoscopy
4.
Dent Mater J ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38644214

ABSTRACT

The delayed mucosal healing of tooth extraction sockets in diabetes has few known effective treatment strategies, and its underlying mechanism remains unknown. Senescent cells may play a pivotal role in this delay, given the well-established association between diabetes, senescent cells, and wound healing. Here, we demonstrated an increase in p21- or p16-positive senescent cells in the epithelial and connective tissues of extraction sockets in type 2 diabetic rats compared to those in control rats. Between 7 and 14 days after tooth extraction, a decrease in senescent cells and improvement in re-epithelialization failure were observed in the epithelium, while an increase in senescent cells and persistence of inflammation were observed in the connective tissue. These results suggest that cellular senescence may have been induced by diabetes and contributed to delayed mucosal healing by suppressing re-epithelization and persistent inflammation. These findings provide new targets for treatment using biomaterials, cells, and drugs.

5.
EBioMedicine ; : 105102, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38614865

ABSTRACT

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

6.
Cancer Sci ; 115(5): 1520-1535, 2024 May.
Article in English | MEDLINE | ID: mdl-38475666

ABSTRACT

Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.


Subject(s)
Cell Proliferation , Colonic Neoplasms , Endothelial Cells , Kallikreins , Liver Neoplasms , Animals , Liver Neoplasms/secondary , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Mice , Colonic Neoplasms/pathology , Colonic Neoplasms/metabolism , Colonic Neoplasms/genetics , Humans , Cell Line, Tumor , Endothelial Cells/metabolism , Endothelial Cells/pathology , Kallikreins/metabolism , Kallikreins/genetics , Tumor Microenvironment , Male , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Cell Movement , Female , Mice, Inbred BALB C
7.
Cancer Sci ; 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38494600

ABSTRACT

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.

8.
Surg Endosc ; 38(5): 2454-2464, 2024 May.
Article in English | MEDLINE | ID: mdl-38459211

ABSTRACT

BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.


Subject(s)
Clinical Competence , Conversion to Open Surgery , Laparoscopy , Laparotomy , Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Female , Male , Japan , Retrospective Studies , Middle Aged , Aged , Conversion to Open Surgery/statistics & numerical data , Proctectomy/methods , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiology
9.
In Vivo ; 38(2): 546-558, 2024.
Article in English | MEDLINE | ID: mdl-38418103

ABSTRACT

BACKGROUND/AIM: Although certain treatment options exist for intestinal incontinence, none are curative. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents, but most preclinical studies of their effectiveness for anal function have used autologous or allogeneic ADSCs. In this study, the effectiveness, timing of administration, and required dosage of human ADSCs were investigated for clinical application. MATERIALS AND METHODS: A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in the following experimental groups (n=4 per group): ADSC (injected ADSCs after injury), PBS (injected phosphate-buffered saline after injury), and control (uninjured). The effects of different timing (immediately after injection and 30 days following injury) and number of human ADSCs administered was compared among groups based on defecation status and pathological evaluation. RESULTS: In terms of defecation status, groups receiving ≥1×104 human ADSCs after injection showed improvement. Pathological images showed that compared to the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥1×104 human ADSCs, and fibrosis of the sphincter was notable in those treated with 1×103 human ADSCs or PBS. Furthermore, defecation status was improved by administration of human ADSCs, not only immediately after injury, but also at 30 days following injury. CONCLUSION: Human ADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥1×104 human ADSCs was the amount necessary to improve defecation status, an effect detected in both the acute and chronic phases.


Subject(s)
Adipose Tissue , Defecation , Humans , Mice , Animals , Stem Cell Transplantation/methods , Adipocytes
10.
Anticancer Res ; 44(2): 695-701, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38307590

ABSTRACT

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.


Subject(s)
Rectal Neoplasms , Venous Thromboembolism , Humans , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Retrospective Studies , Treatment Outcome , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Lymph Nodes/pathology , Rectal Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Neoplasm Recurrence, Local/pathology
11.
Cancer Sci ; 115(3): 723-733, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38263895

ABSTRACT

RNA modifications, including the renowned m6A, have recently garnered significant attention. This chemical alteration, present in mRNA, exerts a profound influence on protein expression levels by affecting splicing, nuclear export, stability, translation, and other critical processes. Although the role of RNA methylation in the pathogenesis and progression of IBD and colorectal cancer has been reported, many aspects remain unresolved. In this comprehensive review, we present recent studies on RNA methylation in IBD and colorectal cancer, with a particular focus on m6A and its regulators. We highlight the pivotal role of m6A in the pathogenesis of IBD and colorectal cancer and explore the potential applications of m6A modifications in the diagnosis and treatment of these diseases.


Subject(s)
Colorectal Neoplasms , Inflammatory Bowel Diseases , Humans , RNA Methylation , Inflammatory Bowel Diseases/genetics , RNA Splicing/genetics , RNA, Messenger/genetics , Colorectal Neoplasms/genetics , RNA
12.
Int J Surg Case Rep ; 114: 109171, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38113563

ABSTRACT

INTRODUCTION: A stoma is commonly created in patients with a high risk of anastomotic leakage. However, patients with obesity have a higher incidence of stoma-related complications, and the decision to create a stoma should be carefully considered. We report two cases of patients with colorectal cancer and super-morbid obesity wherein stoma creation was avoided. PRESENTATION OF CASES: Case 1 involved a 52-year-old male patient with a body mass index (BMI) of 41.8 kg/m2 who underwent a robotic-assisted laparoscopic low anterior resection after neoadjuvant chemotherapy for lower rectal cancer. Although temporary diverting ileostomy was initially considered, stoma creation was skipped intraoperatively, considering the complication risk-benefit ratio. Case 2 involved a 42-year-old female patient with a BMI of 64 kg/m2 who underwent open partial non-curative colon resection for descending colon cancer complicated by colonic perforation and abscess formation. The patient was considered to be at high risk of stoma-related complications due to high mobility of the subcutaneous fat of abdominal wall; therefore, we decided not to create a stoma preoperatively. DISCUSSION: Considering the high risk of stoma-associated complications, avoiding stoma creation and implementing preventive measures against potential complications are alternative options for patients with super-morbid obesity. CONCLUSION: We present our experience two cases in which stoma creation was avoided for super-morbid obese patients with BMI over 40.

13.
Surg Case Rep ; 9(1): 197, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37962718

ABSTRACT

BACKGROUND: Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn's disease, which was curatively resected after preoperative chemoradiotherapy. CASE PRESENTATION: A 49-year-old man who had been diagnosed with Crohn's disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy. CONCLUSION: We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn's disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn's disease.

14.
Anticancer Res ; 43(11): 5061-5066, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37909970

ABSTRACT

BACKGROUND/AIM: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is generally considered a contraindication for curative surgery. In the surgical management of LRRC, sacrectomy is frequently performed to secure clear resection margins. Nonetheless, the indications for high sacrectomy remain controversial due to potential postoperative complications, questions about radicality, and the increased complexity of the operation. Furthermore, comprehensive studies addressing this issue are notably absent. This study aimed to assess the feasibility, safety, and surgical prognosis in high sacrectomy for LRRC. PATIENTS AND METHODS: All patients with LRRC who required concomitant sacrectomy, but did not include the inferior margin of the second sacral vertebra, between 2003 and 2014, were reviewed retrospectively. RESULTS: Eight patients with a median age of 59 years were included in this study. The proximal resection line for sacral bone resection was the central part of the S1 vertebra in one patient, lower edge of the S1 vertebra in six patients, and central part of the S2 vertebra in one patient. Negative margin resection was achieved in five out of the eight patients. The median operative time was 922 min, and the median operative blood loss volume was 6,370 ml. Major complications included pelvic abscess (n=5), ileus (n=1), and pulmonary vein embolism (n=1), none of which proved fatal during the postoperative period. Both the 5-year local re-recurrence-free survival rate and the 5-year distant metastasis-free survival rate were 50% (4/8). CONCLUSION: High sacrectomy is safe and feasible to achieve negative margins in patients with LRRC.


Subject(s)
Rectal Neoplasms , Sacrum , Humans , Middle Aged , Sacrum/surgery , Retrospective Studies , Rectal Neoplasms/surgery , Postoperative Complications , Blood Loss, Surgical , Margins of Excision
15.
Anticancer Res ; 43(12): 5645-5648, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38030168

ABSTRACT

BACKGROUND/AIM: Laparoscopic surgery with pneumoperitoneum is not usually recommended for patients with heart failure due to the potential risks associated with cardiopulmonary stress. Few studies, however, have directly examined whether a laparoscopic approach can be used safely in patients with severe chronic heart failure. PATIENTS AND METHODS: We retrospectively evaluated the safety and feasibility of laparoscopic colorectal cancer surgery in 13 patients with severe chronic heart failure, defined as left ventricular ejection fraction <40% and/or brain natriuretic peptide >100 pg/ml (NT-proBNP >400 pg/ml). Intraoperative hemodynamics, including systolic blood pressure, diastolic blood pressure, mean blood pressure, and heart rate, were carefully monitored. RESULTS: The median left ventricular ejection fraction value was 35% (18-62%), and the median brain natriuretic peptide value was 171.7 pg/ml (109.5-961.4 pg/ml). The time-series mean ratio of the patients' blood pressure and heart rate during surgery indicated that soon after the induction of general anesthesia, mean blood pressure was significantly decreased (p<0.05) from baseline. In all 13 cases, laparoscopic surgery was performed successfully, with no significant complications. CONCLUSION: The present study showed that laparoscopic surgery for colorectal cancer can be performed safely in patients with severe chronic heart failure.


Subject(s)
Colorectal Neoplasms , Heart Failure , Laparoscopy , Humans , Natriuretic Peptide, Brain , Ventricular Function, Left , Stroke Volume , Retrospective Studies , Heart Failure/complications , Heart Failure/surgery , Peptide Fragments , Laparoscopy/adverse effects , Colorectal Neoplasms/complications , Colorectal Neoplasms/surgery , Biomarkers
16.
Commun Biol ; 6(1): 1191, 2023 11 24.
Article in English | MEDLINE | ID: mdl-37996567

ABSTRACT

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/ß-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.


Subject(s)
Colorectal Neoplasms , Neoplastic Cells, Circulating , Humans , CTLA-4 Antigen , Cell Line, Tumor , Wnt Signaling Pathway , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism
17.
Ann Gastroenterol Surg ; 7(6): 968-976, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37927927

ABSTRACT

Aim: To evaluate the feasibility and safety of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) in Japan. Methods: This prospective, multicenter, open-label, single-arm phase II trial was conducted at five institutions. The key eligibility criteria were age ≥ 20 years, LARC within 12 cm from the anal verge, and cT3-4N0M0 or TanyN+M0 at the time of diagnosis that enabled curative resection. Preoperative short-course radiation therapy (SCRT) 5 Gy × 5 days (total 25 Gy) + CAPOX (six courses) followed by total mesorectum excision (TME) was the treatment protocol. Non-operative management (NOM) was allowed if clinical complete response (cCR) was obtained in the preoperative evaluation. The primary endpoint was the pathological complete response (pCR) rate. Results: Thirty patients (male, n = 26; female, n = 4; median age, 62.5 [44-74] years; cT [T2, n = 1; T3, n = 25; T4, n = 4]; cN [N0, n = 13; N1, n = 13; N2, n = 4]) were enrolled. The final analysis included 30 patients in total. The completion rates were 100% for SCRT and 83% for CAPOX. TME and NOM were performed in 20 and seven patients, respectively. pCR was observed in six patients (30% [95% CI 14.0%-50.8%]). The primary endpoint was met. pCR+cCR was observed in 13 (43.3%) patients. There were no treatment-related deaths. Grade ≥3 (CTCAE ver. 5.0) adverse events (≥20%), including diarrhea (23.3%) and neutropenia (23.3%). The median follow-up period was 15.6 (10.5-22.8) months, with no recurrence or regrowth in NOM. Conclusions: ENSEMBLE-1 demonstrated satisfactory pCR and cCR, and well-tolerated safety of TNT for patients with LARC in Japan.

18.
Ann Gastroenterol Surg ; 7(6): 932-939, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37927933

ABSTRACT

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%. Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy.

19.
Oncol Lett ; 26(5): 474, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37809043

ABSTRACT

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.

20.
Cancer Diagn Progn ; 3(5): 597-600, 2023.
Article in English | MEDLINE | ID: mdl-37671313

ABSTRACT

Background/Aim: Recently, robotic surgery for rectal cancer has become a common minimally invasive surgery. In addition, the technology of augmented and mixed reality is applied in various living environments, including medicine. We successfully performed robotic surgery for rectal cancer with three-dimensional (3D) images as mixed reality (MR) using HoloLens2. Case Report: The patient was diagnosed with rectal cancer by colonoscopy and a positron-emission computed-tomography scan, and we performed robot-assisted anterior resection. The operator used HoloLens2 and performed the surgery while visualizing 3D images of pelvic anatomy with the location of the rectal cancer as hologram. The operation was performed completely and safely, and she was discharged 11 days after surgery with no postoperative complications. Conclusion: This case presents the usefulness of a MR system offering organ visualization as hologram during surgery.

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