RESUMO
BACKGROUND: The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM). METHOD: All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses. RESULTS: In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses. CONCLUSION: OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.
Assuntos
Neoplasias Colorretais , Omento , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/cirurgia , Pseudomixoma Peritoneal/patologia , Masculino , Feminino , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Pessoa de Meia-Idade , Omento/cirurgia , Omento/patologia , Idoso , Adulto , Quimioterapia Intraperitoneal Hipertérmica/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Idoso de 80 Anos ou maisRESUMO
Infections and inflammation are profoundly influenced by the extracellular matrix (ECM), but their molecular underpinnings are ill defined. Here, we demonstrate that lumican, an ECM protein normally associated with collagens, is elevated in sepsis patients' blood, while lumican-null mice resolve polymicrobial sepsis poorly, with reduced bacterial clearance and greater body weight loss. Secreted by activated fibroblasts, lumican promotes Toll-like receptor (TLR) 4 response to bacterial lipopolysaccharides (LPS) but restricts nucleic acid-specific TLR9 in macrophages and dendritic cells. The underlying mechanism involves lumican attachment to the common TLR coreceptor CD14 and caveolin 1 (Cav1) in lipid rafts on immune cell surfaces via two epitopes, which may be cryptic in collagen-associated lumican. The Cav1 binding epitope alone is sufficient for cell surface enrichment of Cav1, while both are required for lumican to increase cell surface TLR4, CD14, and proinflammatory cytokines in response to LPS. Endocytosed lumican colocalizes with TLR4 and LPS and promotes endosomal induction of type I interferons. Lumican-null macrophages show elevated TLR9 in signal-permissive endolysosomes and increased response, while wild types show lumican colocalization with CpG DNA but not TLR9, consistent with a ligand sequestering, restrictive role for lumican in TLR9 signaling. In vitro, lumican competes with CD14 to bind CpG DNA; biglycan, a lumican paralog, also binds CpG DNA and suppresses TLR9 response. Thus, lumican and other ECM proteins, synthesized de novo or released from collagen association during ECM remodeling, may be internalized by immune cells to regulate their transcriptional programs and effector responses that may be harnessed in future therapeutics.
Assuntos
Endocitose , Matriz Extracelular/metabolismo , Leucócitos/metabolismo , Lumicana/metabolismo , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Adulto , Animais , Caveolina 1/metabolismo , Membrana Celular/metabolismo , Modelos Animais de Doenças , Endossomos/metabolismo , Fibroblastos/metabolismo , Células HEK293 , Humanos , Ligantes , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fator 88 de Diferenciação Mieloide/metabolismo , Oligodesoxirribonucleotídeos/metabolismo , Omento/patologia , Comunicação Parácrina , Peritônio/patologia , Ligação Proteica , Transporte Proteico , Sepse/microbiologiaRESUMO
Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (LEPR), suppressor of cytokine signaling 3 (SOCS3), sterol regulatory element-binding transcription factor 1 (SREBF1), stearoyl-CoA desaturase-1 (SCD1), and patatin-like phospholipase domain-containing protein 2 (PNPLA2), were determined from liver and adipose tissue. Higher serum leptin and LEPR levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, LEPR was positively correlated with leptin expression in adipose tissue, and SOCS3 was correlated with SREBF1-SCD1. In OAT, SOCS3 was correlated with insulin resistance and transaminase enzymes (p < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.
Assuntos
Tecido Adiposo , Fígado Gorduroso , Leptina , Fígado , Omento , Humanos , Leptina/metabolismo , Feminino , Masculino , Fígado/metabolismo , Pessoa de Meia-Idade , Omento/metabolismo , Omento/patologia , Tecido Adiposo/metabolismo , Adulto , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Receptores para Leptina/metabolismo , Receptores para Leptina/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Resistência à Insulina , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genéticaRESUMO
INTRODUCTION: Lymphangiomas belong to the group of benign vascular tumors that originate in the lymphatic tissue. Up to 90% of cases manifest in children before the second year of life. In adults, their presence is very rare. In most cases, they are located in the head, neck and axilla. Intra-abdominal lymphangiomas are very rare and represent less than 1% of all cases. CASE REPORT: The authors present the case of a 64-year-old female patient diagnosed with an intra-abdominal cystic lesion following a routine examination. A CT scan of the abdomen confirmed a cystic lesion located in the lesser omentum between the left lobe of the liver and the lesser curvature of the stomach. The patient was scheduled for laparoscopic exstirpation of the lesion. Histological examination confirmed the clinical diagnosis of cystic lymphangioma of the lesser omentum. CONCLUSION: The etiopathogenesis of lymphangiomas remains unclear. Despite the fact that they are benign tumors, lymphangiomas tend to have an infiltrative pattern of growth, invading surrounding structures. The majority of cases are asymptomatic and the diagnosis is incidental. The gold standard in treatment remains complete surgical extirpation with microscopically negative margins.
Assuntos
Linfangioma Cístico , Omento , Neoplasias Peritoneais , Humanos , Linfangioma Cístico/cirurgia , Linfangioma Cístico/patologia , Linfangioma Cístico/diagnóstico , Linfangioma Cístico/diagnóstico por imagem , Feminino , Omento/patologia , Omento/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Ovarian cancer (OC) is characterized by frequent widespread peritoneal metastasis. Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote omentum metastasis in OC patients. However, the role of exosomes derived from omental CAFs in metastasis remains unclear. We isolated exosomes from primary omental normal fibroblasts (NFs) and CAFs from OC patients (NF-Exo and CAF-Exo, respectively) and assessed their effect on metastasis. In mice bearing orthotopic OC xenografts, CAF-Exo treatment led to more rapid intraperitoneal tumor dissemination and shorter animal survival. Similar results were observed in mice undergoing intraperitoneal injection of tumor cells. Among the miRNAs downregulated in CAF-Exo, miR-29c-3p in OC tissues was associated with metastasis and survival in patients. Moreover, increasing miR-29c-3p in CAF-Exo significantly weakened the metastasis-promoting effect of CAF-Exo. Based on RNA sequencing, expression assays, and luciferase assays, matrix metalloproteinase 2 (MMP2) was identified as a direct target of miR-29c-3p. These results verify the significant contribution of exosomes from omental CAFs to OC peritoneal metastasis, which could be partially due to the relief of MMP2 expression inhibition mediated by low exosomal miR-29c-3p.
Assuntos
Fibroblastos Associados a Câncer , Exossomos , MicroRNAs , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Animais , Camundongos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Exossomos/metabolismo , Neoplasias Peritoneais/patologia , Omento/metabolismo , Omento/patologia , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Microcystic stromal tumors (MCSTs) are rare ovarian stromal tumors. They harbor CTNNB1 or APC mutations, resulting in ß-catenin nuclear expression. To date, all MCST cases treated with oophorectomy or more extensive surgery have followed benign clinical courses. However, 1 of the 3 cases treated with ovarian cystectomy/tumor resection recurred in the residual ovary and iliac fossa 9 years after ovarian cystectomy. Here, we report a case of recurrent MCST in a 38-year-old woman. The patient underwent ovarian cystectomy for a 7.5 cm solid-cystic right ovarian mass, which showed classic morphological and immunophenotypical features of MCST. Four years later, the tumor recurred in the residual right ovary as a 21 cm mass, involving the pelvic peritoneum and omentum. Molecular analysis using next-generation sequencing revealed a single C TNNB1 exon 3 S37A mutation in the recurrent tumor. To the best of our knowledge, this is the second case of recurrent MCST, which presents more evidence that MCST has the potential to recur and spread locally. Rather than ovarian cystectomy/tumor resection, more aggressive surgery, such as unilateral oophorectomy, may be necessary to decrease the risk of recurrence. Long-term postsurgery follow up is needed, especially after simple ovarian cystectomy/tumor resection.
Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Tumores do Estroma Gonadal e dos Cordões Sexuais , Feminino , Humanos , Adulto , Peritônio/patologia , Omento/cirurgia , Omento/patologia , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/metabolismo , Mutação , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologiaRESUMO
BACKGROUND: The greater omentum is derived from the foregut, and the right hemicolon is derived from the midgut based on developmental anatomy. This study aimed to investigate whether the greater omentum should be resected in laparoscopic complete mesocolic excision based on developmental anatomy for right-sided colon cancer. METHODS: A total of 183 consecutive patients with right-sided colon cancer were recruited in this study between February 2020 and July 2022. Ninety-eight patients underwent standard laparoscopic complete mesocolic excision surgery (CME group). The presence of isolated tumor cells and micrometastases was detected in resected greater omentum by the HE staining and immunohistochemistry analysis. Based on developmental anatomy, laparoscopic CME surgery with greater omentum preservation (DACME group) was proposed and performed on 85 right-sided colon cancer patients. To overcome selection bias, we performed a 1:1 match between two groups using four variables: age, sex, BMI, and ASA scores. RESULTS: No isolated tumor cells and micrometastases were found in the resected greater omentum specimen in the CME group. After the propensity score, 81 pairs were balanced and analyzed. Patients in the DACME group showed shorter operative time (194.9 ± 16.4 min vs.201.5 ± 11.5 min, p = 0.002), less blood loss (23.5 ± 24.7 ml vs.33.6 ± 26.3 ml, p = 0.013), and the shorter hospital stays (9.6 ± 1.7 days vs.10.3 ± 2.0 days, p = 0.010) compared with patients in the CME group. In addition, patients in the DACME group had a lower incidence of postoperative complications (4.9% vs.14.8%, p = 0.035) than patients in the CME group. CONCLUSION: The greater omentum should be preserved during right-sided colon cancer surgery, laparoscopic CME surgery based on developmental anatomy is technically safe and feasible for right-sided colon cancer.
Assuntos
Neoplasias do Colo , Laparoscopia , Mesocolo , Humanos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Resultado do Tratamento , Omento/cirurgia , Omento/patologia , Micrometástase de Neoplasia , Colectomia , Excisão de Linfonodo , Mesocolo/cirurgiaRESUMO
BACKGROUND: A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to establishing innovative chemotherapeutical and surgical strategies without any limitation on rodent models. METHODS: A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with laparoscopic surgery. In phase I trial, 5.0 × 106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0 × 106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns within the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to 4 weeks after inoculation. Tumor tissues disseminated in the peritoneum 4 weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining. RESULTS: In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at 3 weeks after the first inoculation, which increased to 14 and 15 after 4 weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at 4 weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Immunohistochemical H&E and PAX-8 staining confirmed metastatic tumors. CONCLUSIONS: This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cell lines from humans. Using two cell lines, the PM rate is 75%.
Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Animais , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Omento/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Peritônio/patologia , SuínosRESUMO
BACKGROUND: Since 1910, omentectomy has been an essential component of radical gastrectomy for advanced gastric cancer. However, researchers have recently questioned the benefit of omentectomy in radical gastrectomy. The aim of this meta-analysis was to compare omentectomy and omentum preservation in gastrectomy for advanced gastric cancer in terms of survival outcomes and short-term outcomes. METHODS: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched. Studies that compared omentum preservation with omentectomy were included. Overall survival (OS) and relapse-free survival (RFS) were analyzed as primary outcomes. RESULTS: Of 3509 records screened, one randomized clinical trial and five propensity-score matched retrospective studies with 1661 patients were selected. Omentum preservation was associated with improved OS (hazard ratio [HR] = 0.757, 95% confidence interval [CI] = 0.603-0.950, P = 0.016, I2 = 0%), but not with improved RFS (HR = 0.821, 95% CI = 0.668-1.009, P = 0.060, I2 = 9%) compared with omentectomy for advanced gastric cancer. Furthermore, less blood loss and shorter operation time were found in the omentum preservation group than in the omentectomy group. Additionally, the rate of peritoneal recurrence, the number of harvested lymph nodes, and the incidences of postoperative complications and ileus were comparable in the two groups. CONCLUSIONS: Basing on the current literature, gastrectomy with omentum preservation was associated with improved OS and short-term outcomes compared with omentectomy for advanced gastric cancer. Further randomized trials are required to confirm the survival benefit of omentum-preserving gastrectomy.
Assuntos
Neoplasias Gástricas , Gastrectomia , Humanos , Recidiva Local de Neoplasia/patologia , Omento/patologia , Omento/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Although pediatric inguinal hernia (IH) is a very common disease, systematic reviews of herniated organs are scarce. The current study aims to clarify the contents of pediatric IH using preoperative ultrasonography (US) in association with patient age, sex, and risk for developing irreducible/strangulated hernia. METHODS: The medical records of pediatric IH patients who underwent inguinal US examination prior to surgery between 2014 and 2019 were reviewed. Hernia contents were categorized into four groups based on US findings: bowel, omentum, ovary with or without fallopian tube, and ascites. RESULTS: A total of 524 IH lesions found in 220 men and 304 women were analyzed. The most common hernia content in patients under 12 months of age was the bowel (91.0%) in males and ovaries (89.5%) in females. The omentum became the most common herniated organ in both men (78.6%) and women (88.0%) aged 2 years and older. Emergency operations were performed in 3 patients (0.57%) due to irreducible IH, where 2 patients with irreducible ovaries, 5 and 7 months old, developed ovarian torsion and needed to undergo emergent salpingo-oophorectomy. CONCLUSIONS: The contents of pediatric IH depended on patient age and sex. Herniated ovaries in infants can twist in the hernia sac and become strangulated. It is important for clinicians to expect the herniated organ and take appropriate measures in the pediatric primary care setting.
Assuntos
Hérnia Inguinal , Doenças Ovarianas , Criança , Feminino , Hérnia Inguinal/complicações , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/cirurgia , Humanos , Lactente , Masculino , Omento/patologia , Doenças Ovarianas/cirurgia , Salpingo-OoforectomiaRESUMO
We report unexpected death of a 72-year-old man due to a hemoperitoneum (1.9 L of blood in the abdominal cavity). Postmortem examination revealed that the cause of the hemorrhage was an arterial aneurysmal lesion in the greater omentum. The lesion measured 4 × 4 × 6 cm with a generally smooth wall, but with a focal area of rupture within a hemorrhagic region measuring 1 × 2 cm. There was a substantial feeding artery. Histological examination revealed features in keeping with a pseudoaneurysm, but also with some features of a true aneurysm. There was no history of trauma and the rupture of the aneurysmal lesion that had caused the hematoperitoneum was considered to be spontaneous. Prior to his death the deceased had attended hospital for epigastric pain, which was attributed to dyspepsia, but otherwise he had not had symptoms prior to his death.
Assuntos
Falso Aneurisma , Hemoperitônio , Masculino , Humanos , Idoso , Hemoperitônio/etiologia , Hemoperitônio/patologia , Omento/irrigação sanguínea , Omento/patologia , Artérias/patologia , Autopsia , Ruptura EspontâneaRESUMO
Background and Objectives: Surgery remains the only possible curative treatment for advanced gastric cancer (AGC). Peritoneal metastases are estimated to occur in approximately 55-60% AGC patients. Greater omentum is the most common metastatic area in AGC. At present, omentectomy alone or bursectomy are usually carried out during gastric cancer surgery. We performed a meta-analysis in order to evaluate long-term and short-term outcomes among AGC patients, who have undergone radical gastrectomy with or without complete omentectomy (CO). Materials and Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed by use of RevMan (Computer program) Version 5.4. Results: The eight included studies covered an approximately 20 years long study period (2000-2018). Almost all included studies were retrospective ones and originated from Asian countries. Meta-analysis indicated gastrectomy without CO as significantly associated with longer 3-year (RR: 0.94, 95% CI: 0.90-0.98, p = 0.005) and 5-year overall survivals (OS) (RR: 0.93, 95% CI: 0.88-0.98, p = 0.007). Moreover, we found longer operative time (MD: 24.00, 95% CI: -0.45-48.45, p = 0.05) and higher estimated blood loss (MD: 194.76, 95% CI: 96.40-293.13, p = 0.0001) in CO group. Conclusions: Non-complete omentectomy (NCO) group had a statistically greater rate in 3-year and 5-year OSs than the CO group, while the CO group had significantly longer operative time and higher estimated blood loss than the NCO group. Further randomized, possibly multi-center trials may turn out of paramount importance in confirming our results.
Assuntos
Laparoscopia , Neoplasias Gástricas , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Omento/patologia , Omento/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
A 61-year-old woman was diagnosed with a low-absorption tumor measuring 17×5.5×9 cm with fat density between the stomach and transverse colon by follow-up contrast-enhanced CT after surgery for early rectal cancer. The right gastroepiploic artery and vein flowed into the tumor. The tumor demonstrated high signal intensity on contrast-enhanced T2- weighted MRI images, while the overall signal intensity being suppressed on fat-suppressed T2-weighted images. Thus, the patient was diagnosed with primary omental liposarcoma and underwent surgery. The tumor, mainly located on the right omental wall with the right gastroepiploic artery and vein as feeding vessels, was hanging caudally from the greater omentum to the anterior and posterior lobes of the transverse colon. Due to the absence of peritoneal dissemination and infiltration into the surrounding organs, the transverse mesocolon was hollowed out and the entire tumor excised. Based on the histopathological findings, the patient was diagnosed with well-differentiated liposarcoma. Surgical resection is the first-line treatment for liposarcoma, and postoperative adjuvant chemotherapy is ineffective. Since the tumor was completely resected, the patient has survived without recurrence for 2 years and 6 months after surgery.
Assuntos
Colo Transverso , Lipossarcoma , Feminino , Humanos , Pessoa de Meia-Idade , Omento/cirurgia , Omento/patologia , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/cirurgia , Colo Transverso/patologia , Quimioterapia Adjuvante , Peritônio/patologiaRESUMO
Our patient was a 69-year-old man being treated for hyperlipidemia. He was admitted to our hospital with the chief complaint of vomiting and abdominal pain. Abdominal computed tomography(CT)showed dilation of the distal small intestines, a small amount of ascites in the small intestines near the right pelvis, and a closed loop of the small intestine. Enhanced abdominal CT was performed to evaluate intestinal ischemia. Given the adequate blood flow to the wall, the small intestines forming the closed loop, and no increase in ascites, the patient was treated conservatively. Diagnostic laparoscopy was performed because of the narrowed lumen and incomplete obstruction observed on the abdominal CT and contrast- enhanced imaging of the ileal tube. The tip of the appendix adherent to the mesentery of the small intestines, approximately 80 cm from the ileum, and the omentum adherent to the bottom of the right pelvis caused the obstruction. A cord dissection and appendectomy were performed. Making the diagnosis was difficult because there was no history of appendicitis and the small intestinal obstruction was caused by adhesions in 2 places with no history of laparotomy.
Assuntos
Hérnia Interna , Obstrução Intestinal , Intestino Delgado , Idoso , Humanos , Masculino , Apêndice/diagnóstico por imagem , Apêndice/patologia , Ascite/diagnóstico por imagem , Hérnia Interna/complicações , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/cirurgia , Mesentério/diagnóstico por imagem , Mesentério/patologia , Omento/diagnóstico por imagem , Omento/patologia , Aderências Teciduais/complicações , Aderências Teciduais/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The peritoneum, especially the omentum, is a common site for gastric cancer (GC) metastasis. Our aim was to expound the role and mechanisms of Piezo1 on GC omentum metastasis. A series of functional assays were performed to examine cell proliferation, clone formation, apoptosis, Ca2+ influx, mitochondrial membrane potential (MMP) and migration after overexpression or knockdown of Piezo1. A GC peritoneal implantation and metastasis model was conducted. After infection by si-Piezo1, the number and growth of tumours were observed in abdominal cavity. Fibre and angiogenesis were tested in metastatic tumour tissues. Piezo1 had higher expression in GC tissues with omentum metastasis and metastatic lymph node tissues than in GC tissues among 110 patients. High Piezo1 expression was associated with lymph metastasis, TNM and distant metastasis. Overexpressed Piezo1 facilitated cell proliferation and suppressed cell apoptosis in GC cells. Moreover, Ca2+ influx was elevated after up-regulation of Piezo1. Piezo1 promoted cell migration and Calpain1/2 expression via up-regulation of HIF-1α in GC cells. In vivo, Piezo1 knockdown significantly inhibited peritoneal metastasis of GC cells and blocked EMT process and angiogenesis. Our findings suggested that Piezo1 is a key component during GC omentum metastasis, which could be related to up-regulation of HIF-1α.
Assuntos
Regulação Neoplásica da Expressão Gênica , Canais Iônicos/genética , Canais Iônicos/metabolismo , Mecanotransdução Celular , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Mecanotransdução Celular/genética , Potencial da Membrana Mitocondrial , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Omento/patologia , Neoplasias Gástricas/patologiaRESUMO
Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-ß1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/ß-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.
Assuntos
Adipócitos/patologia , Fibroblastos Associados a Câncer/patologia , Omento/patologia , Neoplasias Ovarianas/patologia , Microambiente Tumoral , Células 3T3-L1 , Actinas/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Ascite/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Desdiferenciação Celular/efeitos dos fármacos , Movimento Celular , Proliferação de Células , Feminino , Humanos , Imidas/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Omento/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , Quinolinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Wnt3A/metabolismoRESUMO
The global obesity epidemic is contributing to increased prevalence of diseases fuelled by chronic inflammation, including cancer. Oesophageal adenocarcinoma (OAC) is an obesity-associated malignancy with increasing prevalence, dismal prognosis, and severely dysregulated immune processes. We previously reported that αß T cells migrate to omentum and liver in OAC and contribute to inflammation in these tissues. Here, we assessed the tissue distribution and phenotype of gamma/delta (γδ) T cells in the blood, omentum, liver and tumour of OAC patients. Our data show that the Vδ1 and Vδ3 subsets of γδ T cells are most prevalent in omentum and liver of OAC patients. Furthermore, γδ T cells are predominantly pro-inflammatory in these tissues, and co-express IFN-γ and IL-17. Moreover, γδ T cells exhibit cytotoxic capabilities in OAC omentum and liver. This study provides the first indication that γδ T cells contribute to obesity-associated inflammation in OAC and might be exploited therapeutically.
Assuntos
Adenocarcinoma/imunologia , Neoplasias Esofágicas/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Degranulação Celular , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Imunofenotipagem , Inflamação/complicações , Interferon gama/metabolismo , Interleucina-17/metabolismo , Fígado/imunologia , Fígado/patologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Omento/imunologia , Omento/patologia , Receptores CCR6/metabolismo , Subpopulações de Linfócitos T/patologia , Subpopulações de Linfócitos T/fisiologia , Distribuição TecidualRESUMO
The loss of DYNLL1 contributes to chemoresistance in ovarian cancer. DYNLL1 binds to MRE11, a component of MRN complex (MRE11-RAD50-NBS1), and limits its function in homologous recombination (HR) repair in BRCA1-mutant cells. Decreased activity of MRE11 results in less HR-repair events and thus leads to higher sensitivity against DNA-damaging agents such as cisplatin. Therefore, a better understanding of the cellular changes in DYNLL1-MRN axis in ovarian cancer is needed. Here, we showed that DYNLL1 overexpression leads to decreased chemoresistance even in BRCA-proficient ovarian cancer cells. ATMIN, a transcriptional activator of DYNLL1, showed decreased expression; however, two components of MRN complex, MRE11 and NBS1 (NBN), showed increased expression in high grade compared to low grade serous ovarian cancer. We found that the components of MRN complex (MRE11-RAD50-NBS1) have higher protein levels in sites of omental metastasis and serous tubal intraepithelial carcinoma (STIC) compared to surrounding non-malignant stromal cells in patients with high grade serous ovarian cancer. We showed that the percentage of copy number variation (CNV) events in genes encoding ATMIN, DYNLL1, MRE11 and NBN are the highest in ovarian cancer among other cancer types. ATMIN and DYNLL1 genes are mostly characterized by copy number losses; however, CNV events in MRN complex components are mostly copy number gains. This study highlights the importance of ATMIN-DYNLL1-MRN axis in the development, progression and therapy response of ovarian cancer. MRN levels in ovarian cancer that differ from adjacent, non-malignant tissues may represent actionable therapeutic vulnerabilities.
Assuntos
Cistadenocarcinoma Seroso/patologia , Dineínas do Citoplasma/metabolismo , Progressão da Doença , Complexos Multiproteicos/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais , Fatores de Transcrição/metabolismo , Hidrolases Anidrido Ácido/metabolismo , Proteína BRCA1/metabolismo , Carcinoma in Situ , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Proteína Homóloga a MRE11/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteínas Nucleares , Omento/patologia , Neoplasias Ovarianas/genética , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
Ovarian cancer is uncommon in relation to other women's cancer, however, it is associated with a disproportionate number of deaths due to women's cancer. According to the National Institute of Health, only 1.2% of new cancer diagnoses in the United States are attributed to ovarian cancer, yet it is the fifth leading cause of cancer death in women and is responsible for 2.3% of all female cancer deaths. Ovarian cancer deaths are largely due to widely metastatic and chemoresistant disease that often presents at a late stage. The omentum is one of the most common sites for ovarian cancer metastasis. Recent research findings have highlighted the specific tumor microenvironment of the omentum and how it can be manipulated to prevent ovarian cancer proliferation, metastasis and chemoresistance. Debulking surgery has been the mainstay in the treatment for ovarian cancer. Total omentectomy is classically described as essential to this procedure. This article explores the known benefits of total omentectomy in the surgical treatment of epithelial ovarian cancer as well as the potential benefit contained within the omental tumor microenvironment when the omentum is macroscopically free of disease at the time of initial surgery.
Assuntos
Omento/cirurgia , Neoplasias Ovarianas/cirurgia , Feminino , Humanos , Imunoterapia , Omento/imunologia , Omento/patologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Microambiente TumoralRESUMO
OBJECTIVE: To explore the influence of omentectomy on postoperative outcomes in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Although several meta-analyses have investigated the influence of bursectomy on postoperative outcomes in patients with LAGC, no meta-analyses have explored the influence of omentectomy on postoperative outcomes in such patients. METHODS: We performed a comprehensive electronic search of the literature up to December 2020 to identify studies that compared postoperative outcomes between patients with LAGC who did and did not undergo omentectomy. A meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I2 statistics. RESULTS: Eight retrospective studies involving a total of 2658 patients with LAGC who underwent surgery were included in this meta-analysis. Among them, 3 propensity score matching (PSM) studies demonstrated that the 5-y recurrence-free survival (RFS) rate was 72.9% (314/431) in patients with LAGC who did not undergo omentectomy, whereas it was 70.3% (303/431) in those who did. The results revealed no significant difference in 5-y RFS between groups (RR, 0.91; 95% CI, 0.74-1.13; P = 0.41; I2 = 0%). Two PSM studies also revealed no significant difference in 5-y overall survival (OS) between groups (RR, 0.77; 95% CI, 0.52-1.13; P = 0.18; I2 = 47%). CONCLUSIONS: The results of these meta-analyses show that omentectomy had no significant influence on 5-y OS, especially 5-y RFS, in patients with LAGC.