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1.
Cell Mol Gastroenterol Hepatol ; 17(3): 439-451, 2024.
Article in English | MEDLINE | ID: mdl-38081361

ABSTRACT

BACKGROUND & AIMS: The intestinal epithelium interfaces with a diverse milieu of luminal contents while maintaining robust digestive and barrier functions. Facultative intestinal stem cells are cells that survive tissue injury and divide to re-establish the epithelium. Prior studies have shown autophagic state as functional marker of facultative intestinal stem cells, but regulatory mechanisms are not known. The current study evaluated a post-transcriptional regulation of autophagy as an important factor for facultative stem cell state and tissue regeneration. METHODS: We evaluated stem cell composition, autophagic vesicle content, organoid formation, and in vivo regeneration in mice with intestinal epithelial deletion of the RNA binding protein IGF2 messenger RNA binding protein 1 (IMP1). The contribution of autophagy to resulting in vitro and in vivo phenotypes was evaluated via genetic inactivation of Atg7. Molecular analyses of IMP1 modulation of autophagy at the protein and transcript localization levels were performed using IMP1 mutant studies and single-molecule fluorescent in situ hybridization. RESULTS: Epithelial Imp1 deletion reduced leucine rich repeat containing G protein coupled receptor 5 cell frequency but enhanced both organoid formation efficiency and in vivo regeneration after irradiation. We confirmed prior studies showing increased autophagy with IMP1 deletion. Deletion of Atg7 reversed the enhanced regeneration observed with Imp1 deletion. IMP1 deletion or mutation of IMP1 phosphorylation sites enhanced expression of essential autophagy protein microtubule-associated protein 1 light chain 3ß. Furthermore, immunofluorescence imaging coupled with single-molecule fluorescent in situ hybridization showed IMP1 colocalization with MAP1LC3B transcripts at homeostasis. Stress induction led to decreased colocalization. CONCLUSIONS: Depletion of IMP1 enhances autophagy, which promotes intestinal regeneration via expansion of facultative intestinal stem cells.


Subject(s)
Intestinal Mucosa , Intestines , Animals , Mice , In Situ Hybridization, Fluorescence , Intestinal Mucosa/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Stem Cells/metabolism
2.
Sci Rep ; 13(1): 22217, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097649

ABSTRACT

Osteoprotegerin (OPG) is a secreted cytokine that functions as a decoy receptor for receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL). Anti-RANKL treatment for bone metastasis has been widely accepted for solid tumors. However, the mechanism of OPG-RANKL-RANK signaling in systemic colorectal cancer (CRC) metastasis remains unclear. In this study, we investigated the relevance and function of OPG expression in CRC liver metastasis. First, we performed in silico analysis using The Cancer Genome Atlas public database and found that lower OPG expression in CRC was associated with poor overall survival. Immunohistochemistry analyses using resected specimen from patients with CRC in our institute confirmed the result. Patient-matched primary CRC and liver metastases showed a significant downregulation of OPG expression in metastatic lesions. In CRC cell lines, OPG expression did not suppress cell proliferation and migration. However, OPG expression inhibited macrophage migration by suppressing the RANKL-RANK pathway. Moreover, in vivo mouse liver metastasis models showed that OPG expression in CRC cells suppressed liver metastases. In addition, treatment with an anti-RANKL neutralizing antibody also suppressed liver metastases. These results showed that downregulation of OPG expression in CRC cells promotes liver metastasis by activating tumor-associated macrophage, which can become a candidate for targeted therapy with anti-RANKL neutralizing antibody for CRC liver metastasis.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Animals , Humans , Mice , Antibodies, Neutralizing/metabolism , Colorectal Neoplasms/genetics , Down-Regulation , Liver Neoplasms/genetics , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Receptor Activator of Nuclear Factor-kappa B/genetics , Receptor Activator of Nuclear Factor-kappa B/metabolism , Tumor-Associated Macrophages/metabolism
3.
Int J Mol Sci ; 24(2)2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36674635

ABSTRACT

Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase-DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.


Subject(s)
Colorectal Neoplasms , Extracellular Traps , Animals , Mice , Extracellular Traps/metabolism , Leukocyte Elastase/metabolism , Neutrophils/metabolism , Mice, Nude , Neoplasm Recurrence, Local/pathology , Colorectal Neoplasms/pathology
4.
Clin J Gastroenterol ; 15(5): 941-945, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35902487

ABSTRACT

An 85 year-old woman was transferred with a chief complaint of right thigh pain persisting for 5 days. Abdominal contrast-enhanced computed tomography clearly depicted a swollen appendix incarcerated in the right obturator cavity. She underwent an emergent laparoscopic appendectomy and the simultaneous repair of the obturator hernia. At laparoscopy, appendix was found to be incarcerated in the right obturator canal. The incarcerated appendix was successfully flushed out from the sac by spurting saline into the obturator hernia sac through the catheter inserted into the hernia sac. After a laparoscopic appendectomy, the hernia orifice was repaired using the uterine flap. The patient was discharged from the hospital without any sequelae. This report demonstrates a very rare case of obturator hernia incarcerated with appendix. Although patients with obturator hernia incarcerated with small intestine present with the symptoms related to bowel obstruction, patients with incarceration of appendix do not. Moreover, they would show no typical abdominal symptoms associated with acute appendicitis. Therefore, it is important to perform a radiological evaluation promptly to make a definitive diagnosis when a patient with persisting pain of the right thigh or right ileac fossa with a possibility of obturator hernia with incarceration of the appendix is encountered.


Subject(s)
Appendicitis , Hernia, Obturator , Intestinal Obstruction , Acute Disease , Aged, 80 and over , Appendectomy , Appendicitis/complications , Appendicitis/diagnostic imaging , Appendicitis/surgery , Female , Hernia, Obturator/complications , Hernia, Obturator/diagnostic imaging , Hernia, Obturator/surgery , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Pain
5.
Surg Case Rep ; 8(1): 104, 2022 May 30.
Article in English | MEDLINE | ID: mdl-35644816

ABSTRACT

BACKGROUND: Although small bowel obstruction (SBO) is a major complication occurring after abdominal surgery, few reports have described strangulated SBO after pelvic lymphadenectomy (PL). This report describes two cases of strangulated SBO caused by a skeletonized obturator nerve and pelvic vessels after laparoscopic PL during gynecologic surgery. CASE PRESENTATION: Case 1: A 57-year-old woman with endometrial cancer underwent a laparoscopic semi-radical total hysterectomy with PL. Nine months after the operation, she visited our emergency room complaining about subacute pain spreading in the right groin, right buttock, and dorsal part of the right thigh. She had no abdominal pain. Although her symptoms were not typical, computed tomography (CT) revealed strangulated SBO in the right pelvis. Laparoscopic surgery revealed that the small bowel was ischemic. Then we converted to open surgery. We transected the right obturator nerve and umbilical artery, which constructed an internal hernia orifice in the right pelvis, followed by resection of the ischemic small bowel. Fortunately, during 6-month follow-up, she showed only slight difficulty in walking as a postoperative complication. Case 2: A 62-year-old woman with cervical cancer underwent laparoscopic radical hysterectomy with PL. Six months after the operation, she visited our hospital emergently because of sudden onset of abdominal pain and vomiting. CT showed strangulated SBO. Urgent laparoscopic surgery exhibited the incarcerated small bowel at the right pelvis. Consequently, we converted to open surgery. The terminal ileum was detained into the space constructed by the right umbilical artery. We cut the umbilical artery and performed ileocecal resection. After the surgery, she was discharged with no complication or sequela. CONCLUSION: When examining a patient after PL who complains of severe pain or symptoms, one should consider the possibility of PL-related SBO, even if the pain is apparently atypical for SBO.

6.
Cancer Lett ; 522: 129-141, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34543685

ABSTRACT

Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process that internalizes extracellular fluids into large vesicles called macropinosomes. Recent studies have revealed macropinocytosis's important role in metabolic adaptation to nutrient stress in cancer cells harboring KRAS mutations. Here we showed that KRAS-mutant CRC cells enhanced macropinocytosis for tumor growth under nutrient-depleted conditions. We also demonstrated that activation of Rac1 and phosphoinositide 3-kinase were involved in macropinocytosis of KRAS-mutant CRC cells. Furthermore, we found that macropinocytosis was closely correlated with asparagine metabolism. In KRAS-mutant CRC cells engineered with knockdown of asparagine synthetase, macropinocytosis was accelerated under glutamine-depleted condition, and albumin addition could restore the glutamine depletion-induced growth suppression by recovering the intracellular asparagine level. Finally, we discovered that the combination of macropinocytosis inhibition and asparagine depletion dramatically suppressed the tumor growth of KRAS-mutant CRC cells in vivo. These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers.


Subject(s)
Aspartate-Ammonia Ligase/genetics , Colorectal Neoplasms/therapy , Pinocytosis/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Asparagine/genetics , Asparagine/metabolism , Aspartate-Ammonia Ligase/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Gene Knockdown Techniques , Humans , Mutation/genetics , Phosphatidylinositol 3-Kinases/genetics , rac1 GTP-Binding Protein/genetics
7.
Biomed Pharmacother ; 141: 111887, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34237597

ABSTRACT

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated.


Subject(s)
Colectomy/methods , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/surgery , Laparoscopy/methods , Plant Extracts/administration & dosage , Aged , Colectomy/trends , Colonic Neoplasms/physiopathology , Female , Gastrointestinal Diseases/physiopathology , Gastrointestinal Microbiome/physiology , Herbal Medicine/methods , Herbal Medicine/trends , Humans , Laparoscopy/trends , Male , Middle Aged , Panax , Prospective Studies , Zanthoxylum , Zingiberaceae
9.
Cureus ; 13(6): e15795, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34306864

ABSTRACT

Omental bleeding is potentially life-threatening. There are many causes of omental bleeding including trauma, neoplasia, arterial aneurysm rupture, omental torsion, vasculitis, or segmental arterial mediolysis (SAM). Without remarkable pathological features, the diagnosis of idiopathic omental bleeding is made. Omental bleeding is relatively a rare disease, and there is no established treatment strategy.  A 53-year-old woman was brought to the ED for sudden onset abdominal pain. CT revealed hematoma in the omentum and was diagnosed as idiopathic omental bleeding accordingly. The patient underwent laparoscopic partial omentectomy and was discharged nine days after surgery. The pathological findings of the resected omentum were not remarkable, and the final diagnosis was made as idiopathic omental bleeding. In some case reports of omental bleeding, interventional radiology (IVR) was chosen for hemostasis, but IVR cannot resect tissue of omentum so it is difficult to make a pathological diagnosis. The surgical approach of idiopathic omental bleeding is uncommon. However, the use of the laparoscopic approach hasn't been reported in the literature. Laparoscopic partial omentectomy can provide effective hemostasis. We report laparoscopic partial omentectomy surgical procedure and review of the literature.

10.
JCI Insight ; 6(9)2021 05 10.
Article in English | MEDLINE | ID: mdl-33755595

ABSTRACT

Most colorectal cancers (CRCs) are moderately differentiated or well differentiated, a status that is preserved even in metastatic tumors. However, the molecular mechanisms underlying CRC differentiation remain to be elucidated. Herein, we unravel a potentially novel posttranscriptional regulatory mechanism via a LIN28B/CDX2 signaling axis that plays a critical role in mediating CRC differentiation. Owing to a large number of mRNA targets, the mRNA-binding protein LIN28B has diverse functions in development, metabolism, tissue regeneration, and tumorigenesis. Our RNA-binding protein IP (RIP) assay revealed that LIN28B directly binds CDX2 mRNA, which is a pivotal homeobox transcription factor in normal intestinal epithelial cell identity and differentiation. Furthermore, LIN28B overexpression resulted in enhanced CDX2 expression to promote differentiation in subcutaneous xenograft tumors generated from CRC cells and metastatic tumor colonization through mesenchymal-epithelial transition in CRC liver metastasis mouse models. A ChIP sequence for CDX2 identified α-methylacyl-CoA racemase (AMACR) as a potentially novel transcriptional target of CDX2 in the context of LIN28B overexpression. We also found that AMACR enhanced intestinal alkaline phosphatase activity, which is known as a key component of intestinal differentiation, through the upregulation of butyric acid. Overall, we demonstrated that LIN28B promotes CRC differentiation through the CDX2/AMACR axis.


Subject(s)
Adenocarcinoma/genetics , CDX2 Transcription Factor/metabolism , Cell Differentiation/genetics , Colorectal Neoplasms/genetics , RNA-Binding Proteins/genetics , Racemases and Epimerases/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Animals , Caco-2 Cells , Cell Line, Tumor , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , HCT116 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Mice , Mice, Transgenic , Neoplasm Transplantation , RNA-Binding Proteins/metabolism
11.
Sci Rep ; 11(1): 5027, 2021 03 03.
Article in English | MEDLINE | ID: mdl-33658561

ABSTRACT

Although numerous studies have highlighted the prognostic values of various inflammation-related markers, clinical significance remains to be elucidated. The prognostic values of inflammation-related biomarkers for rectal cancer were investigated in this study. A total of 448 patients with stage II/III rectal cancer undergoing curative resection were enrolled from the discovery cohort (n = 240) and validation cohort (n = 208). We comprehensively compared the prognostic values of 11 inflammation-related markers-derived from neutrophil, lymphocyte, platelet, monocyte, albumin, and C-reactive protein for overall survival (OS) and recurrence-free survival (RFS). Among 11 inflammation-related markers, only "lymphocyte × albumin (LA)" was significantly associated with both OS and RFS in the discovery cohort (P = 0.007 and 0.015, respectively). Multivariate analysis indicated that low LA was significantly associated with poor OS (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.58, P = 0.025), and poor RFS (HR 1.61, 95% CI 1.01-2.80, P = 0.048). Furthermore, using the discovery cohort, we confirmed that low LA was significantly associated with poor OS (HR 2.89, 95% CI 1.42-6.00, P = 0.002), and poor RFS (HR 1.79, 95% CI 1.04-2.95, P = 0.034). LA can be a novel prognostic biomarker for stage II/III rectal cancer.


Subject(s)
Lymphocytes/pathology , Rectal Neoplasms/diagnosis , Serum Albumin/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Platelets/immunology , Blood Platelets/pathology , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , Cohort Studies , Female , Humans , Inflammation , Lymphocyte Count , Lymphocytes/immunology , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology , Neoplasm Staging , Neutrophils/immunology , Neutrophils/pathology , Prognosis , Rectal Neoplasms/immunology , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Serum Albumin/immunology , Survival Analysis
12.
Gan To Kagaku Ryoho ; 48(2): 219-221, 2021 Feb.
Article in Japanese | MEDLINE | ID: mdl-33597363

ABSTRACT

Spontaneous spinal epidural hematomas(SSEH)are rare. The causes of SSEH include hematologic disorders, anticoagulation and antiplatelet therapy, vascular malformations, neoplasms, trauma, or medical interventions, such as epidural catheterization or spinal surgery. However, the cause is usually unclear in most cases. We report a case of SSEH during chemotherapy with paclitaxel and ramucirumab for advanced gastric cancer. A 68-year-old woman was referred to our hospital with a diagnosis of advanced gastric cancer. After 4 courses of neoadjuvant chemotherapy containing S-1 plus oxaliplatin, distal gastrectomy with D2 lymphadenectomy was performed. Postoperative chemotherapy with paclitaxel and ramucirumab was initiated, with a diagnosis of ypStage Ⅲc(T4aN3bM0). She was later transported by ambulance to our hospital with symptoms of sudden onset posterior neck pain and weakness of the extremities. Magnetic resonance imaging(MRI)of her cervical spine showed an epidural hematoma from C2 to C5. The symptoms improved gradually after admission, and the epidural hematoma decreased in size on MRI. Hemorrhagic events such as SSEH should be considered during treatment with angiogenesis inhibitors.


Subject(s)
Hematoma, Epidural, Spinal , Stomach Neoplasms , Aged , Antibodies, Monoclonal, Humanized , Female , Humans , Magnetic Resonance Imaging , Paclitaxel/adverse effects , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Ramucirumab
13.
Inflamm Bowel Dis ; 27(2): 256-267, 2021 01 19.
Article in English | MEDLINE | ID: mdl-32556182

ABSTRACT

BACKGROUND: Defining epithelial cell contributions to inflammatory bowel disease (IBD) is essential for the development of much needed therapies for barrier repair. Children with very early onset (VEO)-IBD have more extensive, severe, and refractory disease than older children and adults with IBD and, in some cases, have defective barrier function. We therefore evaluated functional and transcriptomic differences between pediatric IBD (VEO and older onset) and non-IBD epithelium using 3-dimensional, biopsy-derived organoids. METHODS: We measured growth efficiency relative to histopathological and clinical parameters in patient enteroid (ileum) and colonoid (colon) lines. We performed RNA-sequencing on patient colonoids and subsequent flow cytometry after multiple passages to evaluate changes that persisted in culture. RESULTS: Enteroids and colonoids from pediatric patients with IBD exhibited decreased growth associated with histological inflammation compared with non-IBD controls. We observed increased LYZ expression in colonoids from pediatric IBD patients, which has been reported previously in adult patients with IBD. We also observed upregulation of antigen presentation genes HLA-DRB1 and HLA-DRA, which persisted after prolonged passaging in patients with pediatric IBD. CONCLUSIONS: We present the first functional evaluation of enteroids and colonoids from patients with VEO-IBD and older onset pediatric IBD, a subset of which exhibits poor growth. Enhanced, persistent epithelial antigen presentation gene expression in patient colonoids supports the notion that epithelial cell-intrinsic differences may contribute to IBD pathogenesis.


Subject(s)
Antigen Presentation , Inflammatory Bowel Diseases , Organoids/growth & development , Child , Humans , Inflammation , Inflammatory Bowel Diseases/genetics , Organoids/physiopathology , Up-Regulation
14.
Ann Med Surg (Lond) ; 60: 675-679, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33282280

ABSTRACT

BACKGROUND: The global pandemic of COVID-19 has changed cancer treatment environments. In Japan, cancer screenings were halted and the numbers of endoscopies and surgeries were restricted in some hospitals based on the state of emergency declared. Herein, we investigated the impact of the COVID-19 pandemic on the characteristics of colorectal cancer (CRC) patients in facilities that are on the frontline of both COVID-19 and cancer treatments. PATIENTS AND METHODS: We retrospectively analyzed the cases of all of the CRC patients (n = 123) who underwent surgery at our regional cancer treatment center and tertiary emergency hospital in Japan during a 120-day period ranging from before to after the state of emergency declaration. CRC patients during the corresponding period in the previous year were also examined. RESULTS: Although the number of CRC patients did not show a significant change related to the pandemic, the incidence of obstructive CRCs significantly increased after the pandemic's start. The numbers of outpatients and colonoscopies both decreased, which could have resulted in the decrease of CRC patients detected by cancer screening during the pandemic. The numbers of symptomatic CRC patients and emergency admissions both increased significantly during the pandemic. CONCLUSION: Our findings indicate the possibility that the discovery of CRCs in patients could be delayed due to the halt in screenings caused by the COVID-19 pandemic, resulting in the increase of obstructive CRCs. These results highlight the importance of cancer screening and suggest that the screening system for cancers should be reorganized before future pandemics.

15.
Int Cancer Conf J ; 9(4): 170-174, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32904044

ABSTRACT

Laparoscopic approaches have become a standard strategy for colon cancer patients who undergo surgical treatment. Complete mesocolic excision (CME) with central vascular ligation (CVL) is the fundamental principle of radical resection of colon cancers. Splenic flexure colon cancer (SFCC) is rare, accounting for less than 4% of all colorectal cancer cases. Moreover, a laparoscopic approach for SFCC following the CME/CVL concept can be challenging because the blood supply of the splenic flexure is derived from either the middle colic artery (MCA) branching from the superior mesenteric artery, the left colic artery (LCA) branching from the inferior mesenteric artery. In addition, approximately one third of SFCC patients have an accessory MCA that can originate from the celiac trunk. Herein, we describe the technical procedure of a laparoscopic left hemicolectomy for SFCC using indocyanine green (ICG) for necessary and sufficient lymphadenectomy followed by intracorporeal anastomosis. Two injections of ICG (0.5 mg/0.2 ml × 2) into the subserosa of the proximal and distal sides of the tumor preceded the surgical procedure after pneumoperitoneum. Near infrared images obtained throughout the laparoscopic procedure helped visualize lymphatic drainage vessels and inform decision making for determining vessels requiring ligation according to the CVL concept: MCA, LCA or accessory MCA. Complete intracorporeal anastomosis following necessary and sufficient lymphadenectomy with ICG can minimize the dissecting area of the laparoscopic left hemicolectomy for SFCC patients. Intravenous ICG injection (2.5 mg) after anastomosis helps confirm blood perfusion at the anastomosis site. Four patients with SFCC underwent a laparoscopic colectomy under ICG navigation in 2019 at our institute. The median operative time was 237 min, the median estimated blood loss was 0 ml, and the median number of dissected lymph nodes was 13. No patients experienced postoperative complications. In conclusion, laparoscopic left hemicolectomy with ICG navigation and intracorporeal anastomosis for SFCC patients may be a feasible option for the radical resection of colon cancer.

16.
Int Cancer Conf J ; 9(3): 102-106, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32582511

ABSTRACT

Although the application of laparoscopic rectal surgery has been widely accepted by accumulated evidence, it remains technically difficult in some cases of obesity, narrow male pelvis, bulky tumors, or involvement of adjacent organs. After robotic rectal surgery has been covered by the health insurance system in Japan since April 2018, we have employed robotic rectal surgery for an increasing number of cases by taking advantages of its 3D vision and wrist function. When a colorectal cancer involves the urinary bladder, the surgical treatment of choice is an anterior resection with en bloc (partial or total) bladder resection, depending on the site and extent of bladder involvement. In the attached video, robotic surgery was conducted with the aid of intraoperative cystoscopy, which resulted in curative resection with negative margin. Given that the robotic system provides excellent stability and dexterity for bladder reconstruction, the robotic approach can be technically suitable for locally advanced T4 colorectal cancer with urinary involvement.

17.
Cancer Lett ; 487: 53-62, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32473241

ABSTRACT

Tumor-stromal interaction is implicated in tumor progression. Although CCR1 expression in myeloid cells could be associated with pro-tumor activity, it remains elusive whether disruption of CCR1-mediated myeloid cell accumulation can suppress tumor progression. Here, we investigated the role of CCR1 depletion in myeloid cells in two syngeneic colorectal cancer mouse models: MC38, a transplanted tumor model and CMT93, a liver metastasis model. Both cells induced tumor accumulation of CCR1+ myeloid cells that express MMP2, MMP9, iNOS, and VEGF. Lack of the Ccr1 gene in host mice dramatically reduced MC38 tumor growth as well as CMT93 liver metastasis. To delineate the contribution of CCR1+ myeloid cells, we performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type or Ccr1-/- mice. Mice reconstituted with Ccr1-/- BM exhibited marked suppression of MC38 tumor growth and CMT93 liver metastasis, compared with control mice. Consistent with these results, administration of a neutralizing anti-CCR1 monoclonal antibody, KM5908, significantly suppressed MC38 tumor growth and CMT93 liver metastases. Our findings highlight the importance of the application of CCR1 blockade as a therapeutic strategy.


Subject(s)
Cell- and Tissue-Based Therapy , Colorectal Neoplasms/genetics , Liver Neoplasms/genetics , Protein Serine-Threonine Kinases/genetics , Animals , Bone Marrow/metabolism , Bone Marrow/pathology , Cell Line, Tumor , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Disease Models, Animal , Disease Progression , Gene Expression Regulation, Neoplastic/genetics , Heterografts , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Mice , Myeloid Cells/metabolism , Myeloid Cells/pathology , Neoplasm Metastasis , Nitric Oxide Synthase Type II/genetics , Protein Serine-Threonine Kinases/therapeutic use , Vascular Endothelial Growth Factor A/genetics
18.
Int J Mol Sci ; 20(24)2019 Dec 11.
Article in English | MEDLINE | ID: mdl-31835815

ABSTRACT

The number of colorectal cancer (CRC) patients is increasing worldwide. Accumulating evidence has shown that the tumor microenvironment (TME), including macrophages, neutrophils, and fibroblasts, plays an important role in the development and progression of CRC. Although targeting the TME could be a promising therapeutic approach, the mechanisms by which inflammatory cells promote CRC tumorigenesis are not well understood. When inflammation occurs in tissues, prostaglandin E2 (PGE2) is generated from arachidonic acid by the enzyme cyclooxygenase-2 (COX-2). PGE2 regulates multiple functions in various immune cells by binding to the downstream receptors EP1, EP2, EP3, and EP4, and plays an important role in the development of CRC. The current therapies targeting PGE2 using non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors have failed due to the global prostanoid suppression resulting in the severe adverse effects despite the fact they could prevent tumorigenesis. Therefore, therapies targeting the specific downstream molecules of PGE2 signaling could be a promising approach. This review highlights the role of each EP receptor in the TME of CRC tumorigenesis and their therapeutic potential.


Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Dinoprostone/metabolism , Signal Transduction , Tumor Microenvironment , Animals , Humans , Inflammation/pathology , Molecular Targeted Therapy
19.
Surg Case Rep ; 5(1): 160, 2019 Oct 29.
Article in English | MEDLINE | ID: mdl-31664540

ABSTRACT

BACKGROUND: Internal hemorrhoids are the most common anal diseases. Aluminum potassium sulfate and tannic acid (ALTA) injection is a new sclerosing therapy for the treatment of internal hemorrhoids. Although ALTA injection has been widely used, there are no previous reports of rectal cancer patients who underwent robot-assisted low anterior resection (Rob-LAR) after ALTA injection to treat internal hemorrhoids. CASE PRESENTATION: A 70-year-old man with rectal cancer was presented to our hospital. He had an ALTA injection 2 months before presentation at a clinic due to hematochezia with internal hemorrhoids. The rectal tumor was located 7 cm above the anal verge, and Rob-LAR with the da Vinci Xi system was performed. The patient had sclerosis on the stump of the anal side, which made it difficult to transect the rectum with linear staplers. This required multiple repeats of compression through the SmartClamp feedback. After anastomosis with the double-stapling technique, we constructed a diverting ileostomy. CONCLUSION: Although ALTA injection is a promising strategy for internal hemorrhoids, rectal cancer should be excluded before the sclerosing therapy.

20.
Int Cancer Conf J ; 8(4): 141-145, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31559111

ABSTRACT

Cooperation with multiple departments is essential for the treatment of patients with rectal cancer and other pelvic cancers. In our department, we experienced two cases of rectal cancer that underwent robotic low anterior resection (LAR) and simultaneous resection of other pelvic organs (case 1 with prostatectomy and case 2 with hysterectomy) using the da Vinci Xi system. Here, we show the precise procedures of these two robotic surgeries. Under general anesthesia and lithotomy position, five da Vinci ports were symmetrically placed along the umbilical horizontal line with a 7 cm interval, and a 5 mm AirSeal Access Port was added in the right or left upper quadrant. Patients were placed with 22-degree Trendelenburg and 8-degree tilt to the right. The operators used the center port on the umbilicus as a camera port and chose the docking arms with either two-left-one-right or one-left-two-right setting depending on their preference. This port setting was quite useful for the operators from multiple departments to change the docking arms, even if their preference may be different. Moreover, assistants could use the remaining two ports to provide a well-expanded and safer surgical field. "With a familiar view" and "with a wide view" are our two concepts to safely perform extended pelvic surgeries. We have employed this symmetrical horizontal port site position as a general setting for usual rectal surgeries.

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