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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.
Digestion ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38560978

ABSTRACT

INTRODUCTION: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). METHODS: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested. RESULTS: SOC was positively and independently associated with HRQOL (Mental Health: ß = 0.43, 95% confidence interval [CI] = 0.24-0.61, P < 0.001; General Health: ß = 0.41, 95% CI = 0.23-0.59, P < 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: ß = -0.0082, 95% CI = -0.017 to 0.00064, P = 0.07; that of FIQL by SOC: ß = -0.0052, 95% CI = -0.011 to 0.0010, P = 0.10). CONCLUSIONS: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC.

4.
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
5.
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
6.
Int Immunol ; 36(4): 155-166, 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38108401

ABSTRACT

Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14-/- mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14-/- mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils.


Subject(s)
Colitis, Ulcerative , Eosinophilia , Humans , Mice , Animals , Uridine Diphosphate Glucose/pharmacology , Eosinophils , Inflammation , Intestinal Mucosa , RNA, Messenger , Glucose/adverse effects , Dextran Sulfate , Mice, Inbred C57BL , Disease Models, Animal
7.
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.

8.
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.

9.
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
10.
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
11.
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
12.
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.

13.
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.

14.
Clin J Gastroenterol ; 16(5): 689-692, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37584867

ABSTRACT

Amoebiasis is a parasitic infection caused by the protozoan, Entamoeba histolytica. At times, amoebiasis is activated under immunosuppressive conditions such as chemotherapy. We report a case of fulminant amoebic colitis resulting from an asymptomatic Entamoeba histolytica infection, which was activated by chemotherapy for gastric cancer. The patient developed diarrhea and fever after three courses of chemotherapy for gastric cancer and was diagnosed with acute enteritis. A colonoscopy and biopsy were performed because of the bloody stool. Histopathological findings revealed amoebic invasion of the rectum. Therefore, the patient was diagnosed with amoebic colitis and was treated with metronidazole. Emergency surgery was performed because intestinal perforation was suspected after which his general condition improved and was discharged. Subsequently, gastric cancer surgery was performed and the patient was discharged without postoperative complications. Hence, amoebic colitis should be listed as a differential diagnosis, and a colonoscopic biopsy should be performed when colitis occurs during chemotherapy for cancer.


Subject(s)
Amebiasis , Dysentery, Amebic , Entamoeba histolytica , Stomach Neoplasms , Humans , Amebiasis/complications , Amebiasis/drug therapy , Dysentery, Amebic/drug therapy , Dysentery, Amebic/complications , Dysentery, Amebic/diagnosis , Metronidazole/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Stomach Neoplasms/complications
15.
Anticancer Res ; 43(9): 3913-3921, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37648310

ABSTRACT

BACKGROUND/AIM: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) has become indispensable for staging colorectal cancer but has limitations. Thus, PET with a focus on metabolism other than glucose, mainly amino acid metabolism, has been developed. L-type amino acid transporter 1 (LAT1) is known to be a cancer-specific amino acid transporter and, although 4-Borono-2-(18)F-fluoro-phenylalanine (FBPA) has been reported to be useful as a probe for LAT1, the significance of LAT1 expression in colorectal cancer is ambiguous and implementation of 18F-FBPA-PET in colorectal cancer has not yet been reported. MATERIALS AND METHODS: The aims of this study were to investigate the expression of LAT1 in primary lesions and metastatic lesions of colorectal cancer by immunohistochemical analysis and report the initial experience of performing 18F-FBPA-PET on colorectal cancer patients in clinical practice. RESULTS: There was a significant correlation between LAT1 protein expression in primary tumors and liver metastases. Furthermore LAT-1 expression was positively correlated with recurrence (p=0.033). We performed 18F-FBPA-PET on three rectal cancer patients and detected cancer. CONCLUSION: LAT1 protein is expressed not only in the primary colorectal tumor, but also in liver metastases. 18F-FBPA-PET can be safely performed in patients with colorectal cancer.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Positron Emission Tomography Computed Tomography , Large Neutral Amino Acid-Transporter 1 , Liver Neoplasms/diagnostic imaging , Positron-Emission Tomography , Colorectal Neoplasms/diagnostic imaging , Glucose , Phenylalanine
16.
Ann Surg Oncol ; 30(11): 6913-6924, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37523119

ABSTRACT

PURPOSE: Cancer stem cells (CSCs) are responsible for chemotherapy resistance and have unique properties that protect them from chemotherapy. Investigating CSCs may help to identify the population that is more resistant to treatments, leading to recurrence. We evaluated persisting CSCs, emerging after chemotherapy that cause tumor recurrence. METHODS: Using human colorectal cancer organoids prepared from surgical specimens, we looked at changes in CSCs, the emergence and changes in the original population, which single-cell analysis identified. RESULTS: With regards to changes in cancer stem cell markers, CD44 showed low levels after 5-fluorouracil administration. Once the CD44-ve population was sorted and cultured, the CD44+ve population gradually emerged, and the CD44-ve population decreased. Compared with the CD44-ve population of an organoid parent, the CD44-ve population proliferated after chemotherapeutic agent stimulation. The CD44-ve population was derived from the CD44+ve population before chemotherapeutic agents. In addition, when the CD44 variants were evaluated, the CD44v9 population remained. In single-cell analysis, we found that POU5F1 was highly expressed in the CD44low population. Velocity analysis showed that the CD44-ve population was induced after chemotherapy and expressed POU5F1. POU5F1-EGFP-Casp9 transfected organoids resulted in the appearance of a CD44-ve population after administration of a chemotherapeutic reagent. Both in vivo and in vitro, the dimerizer administration inhibited tumor growth significantly. CONCLUSIONS: POU5F1 is involved in chemotherapy resistance in relation to stemness. For the treatment against refractory tumors, such as the recurrence after chemotherapy, the treatment should target the emerging specific population such as CD44 (or CD44v9) and proliferative cancer cells.


Subject(s)
Hyaluronan Receptors , Neoplasms , Humans , Fluorouracil/pharmacology , Neoplastic Stem Cells , Cell Line, Tumor , Neoplasms/pathology
17.
J Anus Rectum Colon ; 7(3): 217-220, 2023.
Article in English | MEDLINE | ID: mdl-37496563

ABSTRACT

Here we report a case of locally advanced rectal cancer with vaginal invasion, which was successfully resected via laparoscopic surgery using intraoperative indocyanine green (ICG) navigation to determine the vaginal cut line. Based on preoperative examinations, an 81-year-old female was diagnosed with locally advanced rectal cancer with vaginal invasion. After preoperative chemoradiotherapy, the lesion was judged to be resectable. During surgery, the gynecologist transvaginally injected ICG into the vaginal submucosa to determine the caudal margin of the vaginal invasion, and laparoscopically dissected under the near-infrared image of the stained area. Pathological analysis of the resection specimen revealed negative resection margins. One year after surgery, there has been no recurrence.

18.
Ann Gastroenterol Surg ; 7(4): 615-625, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37416732

ABSTRACT

Background: The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD-associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods: This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results: There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse-free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16-3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28-3.63, p = 0.004). Conclusions: Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients.

19.
Surg Case Rep ; 9(1): 104, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37310661

ABSTRACT

BACKGROUND: Metastatic testicular cancer is rare. In particular, primary colorectal cancer rarely metastasizes to the testes. This study reports a case of testicular metastasis recurrence 9 years after the resection of a primary colorectal cancer and a simultaneous metastatic lung tumour. CASE PRESENTATION: A 69-year-old man underwent a laparoscopic left hemicolectomy for descending colon cancer. Preoperative computed tomography revealed a solitary left lung mass. Postoperative chemotherapy reduced the size of the lung mass, and 6 months after the primary resection, the patient underwent a left upper segmentectomy. Based on the pathological examination, he was diagnosed with pulmonary metastasis from colorectal cancer. After four courses of adjuvant chemotherapy, the patient was recurrence-free. However, 9 years and 6 months after the primary resection, he complained of discomfort in his left testicle. Physical examination revealed a left testicular mass. Since a malignancy was not excluded via imaging, left testicular resection was performed to confirm the diagnosis. The pathological diagnosis was testicular metastasis from colorectal cancer. The patient was followed up without medication, and remained healthy, without recurrence, 11 months postoperatively. CONCLUSIONS: It is important to follow up with testicular metastasis in mind, although it is rare.

20.
iScience ; 26(4): 106478, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37091240

ABSTRACT

Somatic cell reprogramming using the microRNAs miR-200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis in CPC;Apc mice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples. c-MAF knockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate-treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.

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