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1.
Proc Natl Acad Sci U S A ; 120(1): e2204269120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574662

RESUMO

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Subpopulações de Linfócitos T/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Memória Imunológica
2.
Carcinogenesis ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868979

RESUMO

BRAF V600E, one of the most frequent mutations in the MAPK pathway, confers poor prognosis to colorectal cancers (CRCs), partly because of chemotherapeutic resistance. Oncogene-induced DNA damage responses (DDRs) that primarily activate p53 are important mechanistic barriers to the malignant transformation of cells; however, the mechanism underlying this impairment in cancer remains unknown. Here, we evaluated the responses of BRAFV600E-induced DDRs in two CRC cell lines, SW48 and LIM1215, both of which harbor wild-type TP53, KRAS, and BRAF. BRAFV600E transduction exhibited distinct phenotypes in these cells: SW48 cell proliferation markedly decreased, whereas that of LIM1215 increased. BRAFV600E expression induced the activation of oncogene-induced DDR signaling in SW48 cells, but not in LIM1215 cells, whereas chemotherapeutic agents similarly activated DDRs in both cell lines. Knockdown experiments revealed that these responses in SW48 cells were mediated by p53-p21 pathway activation. Comet assay (both alkaline and neutral) revealed that BRAFV600E increased single-strand breaks to the same extent in both cell lines; however, in case of LIM1215 cells, it only facilitated double-strand breaks. Furthermore, the proliferation of LIM1215 cells, wherein no oncogene-induced DDRs occurred, was synergistically inhibited upon MDM2 inhibitor-mediated p53 activation combined with MEK inhibition. Taken together, these distinct DDR signaling responses highlight the novel characteristics of BRAFV600E-mutated CRC cells and define the therapeutic potential of p53 activation combined with MAPK inhibition against TP53 wild-type CRC harboring a BRAFV600E mutation.

3.
BMC Cancer ; 24(1): 1027, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164626

RESUMO

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.


Assuntos
Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Neoplasias Retais , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Feminino , Masculino , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Incidência , Adulto , Sacro/cirurgia , Idoso de 80 Anos ou mais
4.
Br J Cancer ; 128(10): 1828-1837, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36869093

RESUMO

BACKGROUND: Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm. METHODS: Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan-Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC. RESULTS: The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells. CONCLUSIONS: The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.


Assuntos
Neoplasias Colorretais , Memória Imunológica , Fatores de Transcrição , Humanos , Linfócitos T CD8-Positivos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Linfócitos do Interstício Tumoral , Células T de Memória , Prognóstico , Fatores de Transcrição/metabolismo
5.
Am J Gastroenterol ; 118(9): 1626-1637, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36988310

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.


Assuntos
Neoplasias do Ânus , Neoplasias Associadas a Colite , Doença de Crohn , Neoplasias Retais , Humanos , Neoplasias do Ânus/patologia , Doença de Crohn/complicações , População do Leste Asiático , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Neoplasias Associadas a Colite/patologia
6.
Am J Pathol ; 192(6): 904-916, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35358474

RESUMO

Most patients with Crohn disease (CD), a chronic inflammatory gastrointestinal disease, experience recurrence despite treatment, including surgical resection. However, methods for predicting recurrence remain unclear. This study aimed to predict postoperative recurrence of CD by computational analysis of histopathologic images and to extract histologic characteristics associated with recurrence. A total of 68 patients who underwent surgical resection of the intestine were included in this study and were categorized into two groups according to the presence or absence of postoperative disease recurrence within 2 years after surgery. Recurrence was defined using the CD Activity Index and the Rutgeerts score. Whole-slide images of surgical specimens were analyzed using deep learning model EfficientNet-b5, which achieved a highly accurate prediction of recurrence (area under the curve, 0.995). Moreover, subserosal tissue images with adipose cells enabled highly accurate prediction. Adipose cell morphology showed significant between-group differences in adipose cell size, cell-to-cell distance, and cell flattening values. These findings suggest that adipocyte shrinkage is an important histologic characteristic associated with recurrence. Moreover, there was a significant between-group difference in the degree of mast cell infiltration in the subserosa. These findings show the importance of mesenteric adipose tissue in patient prognosis and CD pathophysiology. These findings also suggest that deep learning-based artificial intelligence enables the extraction of meaningful histologic features.


Assuntos
Doença de Crohn , Aprendizado Profundo , Adipócitos/patologia , Inteligência Artificial , Colo/patologia , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Humanos , Íleo/patologia , Intestinos/patologia , Mastócitos/patologia , Recidiva
7.
Ann Surg Oncol ; 30(11): 6913-6924, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37523119

RESUMO

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.


Assuntos
Receptores de Hialuronatos , Neoplasias , Humanos , Fluoruracila/farmacologia , Células-Tronco Neoplásicas , Linhagem Celular Tumoral , Neoplasias/patologia
8.
Gan To Kagaku Ryoho ; 50(4): 508-510, 2023 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-37066470

RESUMO

A 61-year-old man presented with dyschezia, and further examination revealed squamous cell carcinoma of the lower rectum invading the bladder and seminal vesicles. The clinical diagnosis was squamous cell carcinoma of the lower rectum, cT4b(bladder and seminal vesicle)N0M0, cStage Ⅱc. Neoadjuvant chemoradiotherapy was administered with external irradiation of the entire pelvis(50.4 Gy/28 Fr)and chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin(FOLFOX). Once tumor shrinkage was observed 3 months after chemoradiotherapy, laparoscopic total pelvic exenteration with TaTME approach was performed. The patient was discharged on the 26th postoperative day without any postoperative complications. Histopathological examination showed only squamous cell carcinoma component with Grade 1a histological treatment effect. The pathological diagnosis was ypT4b(bladder, seminal vesicle)ypN0cM0, ypStage Ⅱc. The patient was alive without any recurrence 6 months after surgery.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Retais , Masculino , Humanos , Pessoa de Meia-Idade , Reto/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila , Pelve/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/tratamento farmacológico
9.
Carcinogenesis ; 43(8): 797-807, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-35640269

RESUMO

The histone methyltransferase G9a is expressed in various types of cancer cells, including colorectal cancer (CRC) cells. Interleukin 8 (IL)-8, also known as C-X-C motif chemokine ligand 8 (CXCL8), is a chemokine that plays a pleiotropic function in the regulation of inflammatory responses and cancer development. Here, we examined the relationship between G9a and IL-8 and the clinical relevance of this association. We immunohistochemically analyzed 235 resected CRC samples to correlate clinical features. Samples with high G9a expression had better overall survival and relapse-free survival than those with low G9a expression. Univariate and multivariate analyses demonstrated that low G9a expression remained a significant independent prognostic factor for increased disease recurrence and decreased survival (P < 0.05). G9a was expressed at high levels in commercially available CRC cell lines HCT116 and HT29. Knockdown of G9a by siRNA, shRNA or the G9a-specific inhibitor BIX01294 upregulated IL-8 expression. The number of spheroids was significantly increased in HCT116 cells with stably suppressed G9a expression, and the number of spheroids was significantly decreased in HCT116 cells with stably suppressed IL-8 expression. Thus, the suppression of IL-8 by G9a may result in a better prognosis in CRC cases with high G9a expression. Furthermore, G9a may suppress cancer stemness and increase chemosensitivity by controlling IL-8. Therefore, G9a is a potential novel marker for predicting CRC prognosis, and therapeutic targeting of G9a in CRC should be controversial.


Assuntos
Neoplasias Colorretais , Antígenos de Histocompatibilidade , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade/genética , Antígenos de Histocompatibilidade/metabolismo , Histona Metiltransferases/genética , Histona Metiltransferases/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Interleucina-8/genética , Ligantes , RNA Interferente Pequeno
10.
World J Surg Oncol ; 20(1): 166, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619103

RESUMO

BACKGROUND: The standard treatment for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, it has been suggested that intensification of neoadjuvant treatment with polychemotherapy in addition to CRT instead of as an adjuvant chemotherapy is better tolerated and associated with a higher pathological complete response (pCR) rate. This concept is known as total neoadjuvant therapy (TNT). Recently, the addition of immunotherapy to preoperative CRT has been reported to be useful in LARC patients with mismatch-repair-deficiency and high levels of microsatellite instability (MSI-H), but there are no reports showing the therapeutic effect of nivolumab in combination with TNT. CASE PRESENTATION: A 23-year-old man had frequent diarrhea. Preoperative examination revealed two adenocarcinomas in the rectum. His maternal grandmother had a rectal cancer patient who developed the disease at age 70s. The larger tumor was located at the peritoneal reflection, and its anterior border close to the prostate (<1 mm); there were eight enlarged pararectal lymph nodes. Considering the size and depth of the tumor, it was judged that radical resection with sufficient margins would be difficult. Therefore, it was decided that TNT would be performed. At first, CAPOX (capecitabine and L-OHP) was administered, followed by preoperative CRT (RT:50.4 Gy and capecitabine). During this period, genetic testing diagnosed this patient as MSI-H, so additional nivolumab was administered after CRT. Colonoscopy revealed that the larger tumor was no longer detectable, so robot-assisted intersphincteric resection and bilateral lateral lymph node dissection was performed. The diagnosis of pCR was made for the larger tumor and partial response was achieved for the smaller tumor, and no lymph node metastasis was found. Major complications were not observed and the patient was discharged on the 14th day after surgery. He was followed up without adjuvant chemotherapy and is alive and recurrence-free after 9 months. CONCLUSION: A case of LARC with MSI-H was treated with TNT with nivolumab, resulting in pCR and complete radical resection. This result suggests that nivolumab in addition to TNT can be an option as a preoperative strategy for LARC with MSI-H.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Adulto , Idoso , Capecitabina , Humanos , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Nivolumabe/uso terapêutico , Neoplasias Retais/patologia , Reto/patologia , Adulto Jovem
11.
Gan To Kagaku Ryoho ; 49(13): 1926-1928, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36733046

RESUMO

BACKGROUND: Perineal wound complications(PWCs)are common after abdominoperineal resection(APR). We examined the incidence of PWCs after APR for anorectal lesions and their risk factors. METHODS: Patients who underwent APR for anorectal lesions at our hospital from January 2011 to December 2021 were included. Complications of Clavien-Dindo Grade Ⅱ or higher were considered as PWCs. RESULTS: Eighty-one patients were included; PWCs were observed in 24 patients (29.6%), and associated with a history of Crohn's disease(p=0.018), longer operation time(p=0.040), higher blood loss (p=0.011), extensive perineal resection(p=0.003), and closure with a skin flap(p=0.003). Forty-one patients underwent APR for initial rectal cancer without extended perineal resection, and PWCs were observed in 9 patients(22.0%). Prognostic nutritional index(PNI)<45(p=0.049), smoking(p=0.034), and alcohol consumption(p=0.021)were associated with PWCs. CONCLUSION: We examined the incidence of PWCs after APR for anorectal lesions and their risk factors. Appropriate intervention in nutrition, smoking, and alcohol consumption may prevent PWCs.


Assuntos
Doença de Crohn , Procedimentos de Cirurgia Plástica , Protectomia , Neoplasias Retais , Humanos , Retalhos Cirúrgicos/patologia , Retalhos Cirúrgicos/cirurgia , Neoplasias Retais/patologia , Doença de Crohn/complicações , Protectomia/efeitos adversos , Períneo/cirurgia , Períneo/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
12.
J Hum Genet ; 66(7): 659-669, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33486503

RESUMO

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women's opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC (p = 0.05). Sixty-two women (54.4%) preferred a duration of 15-29 min for pretest GC sessions, followed by 30-59 min (28.9%) and <15 min (14.9%). Women's preference of ≥30 min in length was significantly associated with anhedonia, singleton pregnancies, acquaintance with people with trisomy 21, and awareness of prenatal testing. Women who were unaware of the need for agreement with the partner for prenatal testing and who did not know the average life expectancy of a trisomy 21 patient significantly preferred <15 min in length over other durations. While the majority of women preferred in-person GC for <30 min, their preferences varied by their background characteristics, experiences, attitudes, and knowledge. These findings will help establish a prenatal GC system offering a choice of GC models in Japan; however, further large-scale studies are needed to confirm these findings.


Assuntos
Aconselhamento Genético/tendências , Testes Genéticos/tendências , Gestantes/psicologia , Diagnóstico Pré-Natal , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Japão/epidemiologia , Preferência do Paciente , Gravidez , Inquéritos e Questionários
13.
Surg Today ; 50(3): 292-297, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31595366

RESUMO

PURPOSE: We examined the association between pathological lateral pelvic lymph node (LPLN) metastasis and the LPLN diameter in patients with locally advanced rectal cancer (LARC) who received a neoadjuvant chemotherapy (NAC) regimen based on oxaliplatin as induction chemotherapy. We aimed to determine whether or not the LPLN size predicts LPLN metastasis in NAC cases. METHODS: We retrospectively examined data from 3 institutes for 60 patients with LARC who received mesorectal excision and LPLN dissection after NAC. We evaluated the LPLN size on magnetic resonance imaging (MRI) scans acquired before and after NAC. We performed multivariate analyses to analyze the relationship between the LPLN size and clinicopathological factors. RESULTS: For patients with visible LPLNs, the median short-axis diameter (SA) was significantly reduced from 5.1 mm (range 2.0-17.4) before NAC to 3.7 mm (range 2.1-19.0) after NAC (p = 0.0479). SA diameters were significantly larger in pathological LPLNs than in healthy LPLNs, both before (p = 0.0002) and after NAC (p < 0.0001). A SA cut-off value of 7 mm before NAC was able to independently predict lymph node metastasis (p = 0.0178). CONCLUSIONS: We showed that MRI-based evaluations of LPLN size were able to predict metastasis in patients who underwent NAC for LARC. This finding might be useful when considering selective LPLN dissection in NAC cases.


Assuntos
Quimioterapia Adjuvante , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Neoplasias Retais/terapia , Humanos , Quimioterapia de Indução , Oxaliplatina/administração & dosagem , Valor Preditivo dos Testes , Estudos Retrospectivos
14.
Digestion ; 99(3): 194-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30343293

RESUMO

BACKGROUND/AIMS: There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn's disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell -subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn's disease (CDi). METHODS: We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14-CD11c-, CD14-CD11c+, and CD14+CD11c+CD163low cells from NC and CDi. RESULTS: Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. CONCLUSION: Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.


Assuntos
Colo/patologia , Doença de Crohn/imunologia , Imunidade Inata , Mucosa Intestinal/patologia , Células Mieloides/imunologia , Colo/citologia , Colo/imunologia , Biologia Computacional , Doença de Crohn/patologia , Perfilação da Expressão Gênica , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Células Mieloides/patologia , Análise de Sequência de RNA , Transcriptoma/imunologia
16.
Surg Case Rep ; 10(1): 111, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700734

RESUMO

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.

17.
Surg Case Rep ; 10(1): 186, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39138697

RESUMO

BACKGROUND: An enterocutaneous fistula (ECF) is defined as an abnormal communication between the gastrointestinal tract and skin. ECFs are rarely encountered in clinical practice, yet are frequently difficult to treat. Few reports exist regarding the surgical techniques for the treatment of an ECF. Therefore, we report a case of refractory ECF with concomitant severe adhesions, in which we performed combined laparoscopic adhesiolysis and planned open conversion. CASE PRESENTATION: A 57-year-old female patient underwent a laparotomy for an ovarian cyst in her 20s. At 46 years, adhesiolysis without bowel resection was performed for adhesive small bowel obstruction (SBO). However, her symptoms did not improve. Eighteen days postoperatively, she underwent a reoperation and jejunostomy. An ECF developed post-reoperation; therefore, stoma closure and radical surgery for the ECF were planned. Due to the severe adhesions, only stoma closure was performed, based on intraoperative assessments. The patient was subsequently referred to our hospital. First, skin care around the fistula was provided during an outpatient visit. Appropriate sizing of the stoma pouch was performed, to improve erosions and ulcers. Thereafter, debridement of the perifistula skin and simple closure of the ECF outlet were attempted; however, the ECF recurred shortly thereafter. After 8 years of regular skin care, with the ECF remaining stable, however, manifesting as symptomatic SBO, she underwent laparoscopic adhesiolysis. This procedure was initiated in the epigastric region, where relatively fewer adhesions were anticipated. Post-open conversion, partial resection of the small intestine at four locations, including the fistula site, was performed. Postoperatively, jejunal edema and peristaltic dysfunction, due to narrowing of the superior mesenteric artery occurred. Regular drainage by percutaneous endoscopic gastrostomy was required. However, she improved and was discharged 3 months post-operatively. Three years post-operatively, the ECF and SBO did not recur. CONCLUSIONS: We reported a case of refractory ECF in which we were able to safely perform surgery, by combining laparoscopic adhesiolysis and a planned open conversion. Therefore, the surgical approach used in this case may be an option for securing a safe surgical field, while avoiding collateral damage.

18.
Anticancer Res ; 44(2): 695-701, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307590

RESUMO

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.


Assuntos
Neoplasias Retais , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias Retais/patologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva Local de Neoplasia/patologia
19.
Cancer Diagn Progn ; 4(3): 264-269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707722

RESUMO

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.

20.
In Vivo ; 38(5): 2565-2569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39187314

RESUMO

BACKGROUND/AIM: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function. CASE REPORT: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder. CONCLUSION: The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery.


Assuntos
Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica Transanal/métodos , Instrumentos Cirúrgicos , Resultado do Tratamento
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