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BACKGROUND: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. METHODS: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. RESULTS: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. CONCLUSIONS: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.
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Increased expression of CD24 and MET, markers for cancer stem-like cells (CSCs), are each associated with ovarian cancer severity. However, whether CD24 and MET are co-expressed in ovarian CSCs and, if so, how they are related to CSC phenotype manifestation remains unknown. Our immunohistochemistry analysis showed that the co-expression of CD24 and MET was associated with poorer patient survival in ovarian cancer than those without. In addition, analyses using KM plotter and ROC plotter presented that the overexpression of CD24 or MET in ovarian cancer patients was associated with resistance to platinum-based chemotherapy. In our miRNA transcriptome and putative target genes analyses, miR-181a was downregulated in CD24-high ovarian cancer cells compared to CD24-low and predicted to bind to CD24 and MET 3'UTRs. In OV90 and SK-OV-3 cells, CD24 downregulated miR-181a expression by Src-mediated YY1 activation, leading to increased expression of MET. And, CD24 or MET knockdown or miR-181a overexpression inhibited the manifestation of CSC phenotypes, cellular quiescence-like state and chemoresistance, in OV90 and SK-OV-3 cells: increased colony formation, decreased G0/G1 phase cell population and increased sensitivity to Cisplatin and Carboplatin. Our findings suggest that CD24-miR-181a-MET may consist of a signalling route for ovarian CSCs, therefore being a combinatory set of markers and therapeutic targets for ovarian CSCs.
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PURPOSE: Ubiquitin-conjugating enzyme E2 C (UBE2C) is known to show a causal relationship with cancer development and advancement. The role of UBE2C is to control the mitotic spindle checkpoint. Excess UBE2C has been identified in patients with advanced prostate cancer. The objective of the present study was to examine positive connections between the expression of UBE2C and prognostic factors for prostate cancer. METHODS: Prostate cancer patients' clinical data were analysed. Tissue microarrays (TMAs) were also performed for human prostate cancer tissues (n = 335) and adjacent non-neoplastic tissues (n = 22). TMA slides were incubated with antibodies against UBE2C. Cores were scored by a pathologist who was blind to cancer results. RESULTS: Of 335 prostate cancer patients, 200 could be assessed for biochemical recurrence, clinical recurrence, and overall survival. Human prostate cancer tissues showed higher expression of UBE2C than adjacent non-neoplastic tissues. High expression level of UBE2C showed a strong positive relationship with a high prostate-specific antigen (PSA), Gleason's score, and pathological stage of prostate cancer. Patients with a higher UBE2C grade demonstrated greater lymphatic engagement of prostate cancer than those with a lower UBE2C grade. CONCLUSION: The expression of UBE2C has positive correlations with several prognostic factors for prostate cancer. Thus, investigating the expression level of UBE2C staining is a promising tool for predicting prostate cancer prognosis.
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Neoplasias de la Próstata , Enzimas Ubiquitina-Conjugadoras , Masculino , Humanos , PronósticoRESUMEN
BACKGROUND: Thoracic actinomycosis is an uncommon, chronic, and progressive infection, especially in patients with HIV. We report a case of thoracic actinomycosis presenting as an isolated pleural effusion in a patient with an HIV infection. CASE PRESENTATION: A 68-year-old patient with progressive dyspnea and fever was admitted. On the right side, an ipsilateral massive pleural effusion was confirmed on the chest radiograph, and an HIV infection was newly diagnosed. A pleural biopsy was performed for the further differential diagnosis of potential opportunistic infections and malignancies. The pathology findings were consistent with actinomycosis. CONCLUSIONS: Active diagnostic approaches such as a pleural biopsy should be considered for indeterminate pleural effusions in immunocompromised patients.
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Actinomicosis , Infecciones por VIH , Enfermedades Pulmonares , Derrame Pleural , Actinomicosis/diagnóstico , Actinomicosis/tratamiento farmacológico , Anciano , Biopsia , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Derrame Pleural/diagnósticoRESUMEN
BACKGROUND: The mTOR signaling pathway is inactivated by AMPK's tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. METHODS: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. RESULTS: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox's proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. CONCLUSION: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.
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INTRODUCTION: Although several studies have been conducted to evaluate the feasibility of Raman spectroscopy (RS) for the diagnosis of bladder cancer (BCa), it is difficult to use RS in real clinical settings based on the current limited evidence. Therefore, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of RS in BCa. MATERIALS AND METHODS: Comprehensive literature searches were performed in the PubMed/Medline, Embase, and Cochrane Library databases up to March 2019. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this study included reports according to the participant, intervention, comparator, outcomes, and study design approach. The methodological quality of the included studies was evaluated according to questionnaires and criteria suggested by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The quantitative outcomes included diagnostic accuracy (sensitivity and specificity). RESULTS: Fifteen studies were included for qualitative analysis and four studies (BCa cases, n = 139; control cases n = 107) were included in this analysis by screening the full text of the remaining articles based on the inclusion and exclusion criteria through a systematic review. The pooled sensitivity and specificity of RS were 0.91 (95% confidence interval [CI]: 0.85-0.95) and 0.93 (95% CI: 0.86-0.97), respectively. The among-study heterogeneity was statistically significant in the specificity results (Cochran Q statistic, P = 0.015; I2 statistic, 71.3%) but not in the sensitivity results (Cochran Q statistic, P = 0.189; I2 statistic, 37.2%). CONCLUSIONS: RS showed the potential to be an efficient tool with high accuracy for detecting malignant bladder lesions. More studies with in vivo real-time settings are warranted to validate our results.
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Cistoscopía/métodos , Espectrometría Raman , Neoplasias de la Vejiga Urinaria/diagnóstico , Vejiga Urinaria/patología , Estudios de Factibilidad , Humanos , Biopsia Líquida/métodos , Sensibilidad y Especificidad , Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Orina/citologíaRESUMEN
The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs.
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Glomerulonefritis por IGA , Podocitos , Membrana Basal Glomerular , Mesangio Glomerular , Humanos , ProteinuriaRESUMEN
BACKGROUND: Although various studies have been conducted to demonstrate the possibility of Raman spectroscopy (RS) as a diagnostic tool for prostate cancer (PC), it is difficult to use it in the real clinical area because of imitations in various research processes. Therefore, we did a systematic review and meta-analysis about the accuracy in diagnostic use of RS for PC. METHODS: A literature search was done using PubMed, Embase, and Cochrane library databases in March 2019 to analyze the accuracy of RS for diagnosis of PC. The accuracy of RS for diagnosis of PC was evaluated by means of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC). RESULTS: Five studies were included for qualitative analysis by screening the remaining articles according to the inclusion and exclusion criteria by means of a systematic review. The pooled sensitivity and specificity of RS were 0.89 (95% CI: 0.87-0.91) and 0.91 (95% CI: 0.89-0.93), respectively. The overall PLR and NLR were 9.12 (95% CI: 4.15-20.08) and 0.14 (95% CI: 0.07-0.29), respectively. The DOR of RS demonstrated high accuracy (73.32; 95% CI: 18.43-291.73). The area under the curves (AUCs) of SROC curves was 0.93. CONCLUSIONS: RS is an optical diagnostic method with high potential for diagnosis and grading of PC and has advantages of real-time and convenient use. In order to consider real-time use of RS in an actual clinical setting, more studies for standardization and generalization of RS performance and analytical method must be conducted.
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BACKGROUND: Thrombotic microangiopathy (TMA), a rare but serious complication of systemic lupus erythematosus (SLE), is associated with poor outcomes to conventional immunosuppressive therapy. Recently, eculizumab, a humanised monoclonal antibody that blocks the complement factor 5, has been known to effectively treat atypical haemolytic uremic syndrome (aHUS). Here, we report a case of aHUS co-existing with lupus nephritis that was successfully treated with eculizumab. CASE PRESENTATION: A 23-year-old man presented with abdominal pain and diarrhoea. Initial laboratory tests have shown thrombocytopaenia, microangiopathic haemolytic anaemia, and acute kidney injury. Immunologic tests were consistent with SLE. Kidney biopsy have revealed lupus nephritis class IV-G with TMA. Genetic analysis have shown complement C3 gene mutations, which hints the co-existence of lupus nephritis with aHUS, a form of complement-mediated TMA. Although initial treatment with haemodialysis, plasma exchange, and conventional immunosuppressive therapy (steroid and cyclophosphamide) did not appreciably improve kidney function and thrombocytopaenia, the patient was able to respond to eculizumab therapy. CONCLUSIONS: Due to the similar features of TMA and SLE, clinical suspicion of aHUS in patients with lupus nephritis is important for early diagnosis and prompt management. Timely administration of eculizumab should be considered as a treatment option for aHUS in lupus nephritis patients to yield optimal therapeutic outcomes.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Inactivadores del Complemento/uso terapéutico , Mutación , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/genética , Complemento C3/genética , Humanos , Nefritis Lúpica/complicaciones , Masculino , Adulto JovenRESUMEN
BACKGROUND: Papillary thyroid cancer (PTC) has good prognosis so that the local recurrence or distant metastasis can occur later on the lifetime follow up. In this study, we report recurrence of PTC in subcutaneous area combined with lymph node metastasis. A suspicion of needle tract implantation after core needle biopsy was found. CASE SUMMARY: A 66-year-old female patients who underwent right thyroid lobectomy for PTC complained of palpable nodule on anterior neck area. The location of the palpable nodule was not associated with her postoperative scar. After excision of the skin tumor, it was diagnosed as recurrence of PTC. Furthermore, results of subsequent imaging showed lymph node metastasis on her right cervical area. According to the previous medical records, the patient received core needle biopsy through the neck of the patient midline and hematoma was noted after the procedure. The time interval from the first diagnosis to local recurrence or metastasis to the skin and lymph nodes was ten years. As treatment, the patient underwent lymph node dissection in the right and completion thyroidectomy for radioisotope treatment. CONCLUSION: Needle tract implantation can occur after core needle biopsy. Further studies are needed to compare core-needle biopsy and fine-needle aspiration.
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BACKGROUND: A cutaneous ciliated cyst (CCC) is a rare, benign tumor in young female adults, which is usually found on the lower extremities. CASE SUMMARY: We found an uncommon location of CCC in the anterolateral cervical area and reviewed the literature. A 20-year-old female complained of a well-defined, painless, palpable mass that started several years ago. The mass was tense and movable and located at the anterolateral aspect of the neck. Imaging showed a non-enhancing round mass. Surgical excision biopsy was performed, and the cystic mass was revealed to be a CCC. CONCLUSION: The rare location of CCC can be found in anterior neck area, which should be another diagnostic option for mass on anterior neck.
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Scleromyxedema is a rare connective tissue disorder characterized by a generalized lichenoid eruption and sclerodermoid induration with histologic features of dermal mucin deposition. A 44-year-old man presented with a 3-year history of generalized progressive skin thickening and sclerosis. He had diffuse skin-colored to erythematous firm papules coalescing into indurated plaques over his whole body. He had been diagnosed with scleromyxedema from a skin biopsy with monoclonal gammopathy of undetermined significance (MGUS) at another tertiary hospital 3 years earlier. He had been treated with systemic corticosteroids and methotrexate, but his systemic symptoms (dyspnea, dysphagia, skin swelling, and induration) had worsened over the past year, so he visited our clinic seeking further evaluation and management. The patient received high-dose intravenous immunoglobulin (IVIG) therapy once a month in combination with systemic corticosteroids. After three courses of IVIG, his cutaneous symptoms and dyspnea had improved dramatically. Herein we report a case of scleromyxedema with systemic involvement with significant improvement following IVIG therapy.
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Erupciones Liquenoides , Escleromixedema , Adulto , Biopsia , Humanos , Inmunoglobulinas Intravenosas , Masculino , Escleromixedema/diagnóstico , Escleromixedema/tratamiento farmacológico , PielAsunto(s)
Ataxia Cerebelosa , Enfermedades Cerebelosas , Neoplasias Ováricas , Degeneración Cerebelosa Paraneoplásica , Enfermedad Aguda , Ataxia Cerebelosa/etiología , Enfermedades Cerebelosas/etiología , Femenino , Humanos , Neoplasias Ováricas/complicaciones , Degeneración Cerebelosa Paraneoplásica/diagnóstico , Degeneración Cerebelosa Paraneoplásica/etiologíaRESUMEN
Mitochondrial injury plays important roles in the pathogenesis of various kidney diseases. However, mitochondrial injury in IgA nephropathy (IgAN) remains largely unexplored. Here, we examined the associations among mitochondrial injury, IgAN, and treatment outcomes. We prospectively enrolled patients with IgAN and age-/sex-matched healthy volunteers (HVs) as controls (n = 31 each). Urinary copy numbers of the mitochondrial DNA (mtDNA) genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured. Urinary mtDNA levels were elevated in the IgAN group compared with that in HVs (p < 0.001). Urinary ND1 levels were significantly higher in the low proteinuria group than in the high proteinuria group (p = 0.027). Changes in urinary levels of ND1 and COX3 were positively correlated with changes in proteinuria (p = 0.038 and 0.024, respectively) and inversely correlated with changes in the estimated glomerular filtration rate (p = 0.033 and 0.017, respectively) after medical treatment. Mitochondrial injury played important roles in IgAN pathogenesis and may be involved in early-stage glomerular inflammation, prior to pathological changes and increased proteinuria. The correlation between changes in urinary mtDNA and proteinuria suggest that these factors may be promising biomarkers for treatment outcomes in IgAN.
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Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Glomerulonefritis por IGA , Mitocondrias , Adulto , ADN Mitocondrial/genética , ADN Mitocondrial/orina , Femenino , Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/orina , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/genética , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Estudios ProspectivosRESUMEN
Asia has the highest incidence of Henoch-Schönlein purpura (HSP). Although 50% to 75% of patients with HSP manifest gastrointestinal (GI) symptoms, endoscopic, and pathologic findings of HSP have been rarely reviewed in Asia.Patients diagnosed with HSP who had undergone endoscopic biopsy from GI tract (GIT) in Soonchunhyang University Seoul Hospital from 2000 to 2018 were evaluated and 25 cases with 44 biopsies from upper GI tract (U-GIT) or lower GI tract (L-GIT) were enrolled. Their clinical and endoscopic findings and histologic findings of endoscopic biopsy were reviewed.Of the 25 patients, 15 were males and 10 were females. There were 6 children and 19 adults. The most common GI symptom was abdominal pain (20/25), followed by loose stool or diarrhea (9/25). Biopsied sites included 19 from U-GIT (9 stomach and 10 duodenum) and 25 from L-GIT (7 terminal ileum, 1 cecum, 4 ascending, 1 transverse, 2 descending, 7 sigmoid, and 3 rectum). Erythema/petechia was the most common endoscopic finding in U-GIT, while erosion/ulceration was the most common one in L-GIT. In U-GIT, extravasted red blood cell (RBC) (14/19) was the most common histologic finding, while leukocytoclastic vasculitis (LCV)/capillarities were identified in 7 specimens, including 5 duodenum samples. In endoscopic investigations of L-GIT, erosion/ulceration (9/14) was predominantly identified. The most common histologic finding was also extravasted RBC (22/25), while LCV/capillarities were noted in 10 specimens, including 5 specimens from terminal ileum.The HSP commonly involves GIT. Histologic findings of our cases were not significantly different from results of previous studies in Western countries. However, endoscopic and pathologic characteristics of HSP have been rarely reviewed in Asia. Herein, we share experience of endoscopic biopsy of GIT in patients with HSP.
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Endoscopía Gastrointestinal/métodos , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/patología , Vasculitis por IgA/complicaciones , Vasculitis por IgA/patología , Adolescente , Adulto , Asia , Eritema/etiología , Eritema/patología , Femenino , Humanos , Incidencia , Masculino , Úlcera Péptica/etiología , Úlcera Péptica/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.
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Quimiocinas/metabolismo , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Enfermedad de Still del Adulto/inmunología , Enfermedad de Still del Adulto/patología , Adulto , Calgranulina A/sangre , Calgranulina A/metabolismo , Calgranulina B/sangre , Calgranulina B/metabolismo , Quimiocina CXCL10/sangre , Quimiocina CXCL10/metabolismo , Quimiocina CXCL13/sangre , Quimiocina CXCL13/metabolismo , Quimiocinas/sangre , Diagnóstico Diferencial , Femenino , Linfadenitis Necrotizante Histiocítica/diagnóstico , Humanos , Inmunohistoquímica , Ligandos , Linfadenitis/diagnóstico , Linfoma de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Receptores CXCR3/metabolismo , Estudios Retrospectivos , Enfermedad de Still del Adulto/diagnóstico , Receptor Toll-Like 4/metabolismo , Tuberculosis Ganglionar/diagnósticoRESUMEN
BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is a novel method for in vivo histological analysis of colorectal neoplasm mucosa, which provides meaningful information for the development of adequate therapeutic strategies. However, the in vivo histology of colorectal neoplasm submucosa has not been studied. We assessed the feasibility and safety of pCLE for evaluating colorectal submucosa, and identified and validated diagnostic criteria for submucosal carcinoma infiltration. METHODS: From March to July 2014, 83 pCLE videos of 51 lesions in 31 patients who underwent scheduled colonoscopic procedures for the removal of colorectal neoplasms were acquired consecutively. During the procedures, pCLE videos of the lesions and biopsy samples for histopathological analysis were acquired. Final histopathological results were used as the gold standard. RESULTS: Based on the confocal pattern, we classified colorectal submucosa findings as negative (superficial submucosa, deep submucosa, and submucosa with fibrosis) or indicative of carcinoma infiltration. Dark and irregular cell nests with irregular cell architecture and little or no mucin were seen in submucosal carcinoma infiltration. Based on rates of correlation with pathological findings, the sensitivity, specificity, and accuracy of the classification of submucosal carcinoma infiltration by two observers were 91.7, 86.8, and 88.0 %, respectively. In addition, the results showed good interobserver agreement for the detection of submucosal carcinoma infiltration (κ = 0.757, standard error = 0.102). No adverse events occurred during the procedures. CONCLUSIONS: Submucosa assessment by pCLE is feasible and safe. pCLE is useful for the differentiation of normal submucosa from carcinoma infiltration, particularly when infiltration is accompanied by severe fibrosis. Large-scale prospective studies are needed to further evaluate the clinical impact of the use of pCLE during endoscopy.
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Adenocarcinoma/patología , Adenoma/patología , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Mucosa Intestinal/patología , Microscopía Confocal/métodos , Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Anciano , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Microscopía Intravital , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The prediction of biologic behavior of poorly cohesive early gastric carcinoma (EGC) is an important issue in the selection of the treatment modality. To elucidate the risk factors for lymph node metastasis (LNM) of poorly cohesive EGC, we focused on the histologic purity of the poorly cohesive component and evaluated the impact of this factor on LNM. METHODS: We divided poorly cohesive EGC into (1) pure signet ring cell (SRC) carcinoma, which was defined as composed only of signet ring cells or poorly cohesive cells and (2) mixed SRC carcinoma, defined as poorly cohesive carcinoma with minor tubular components. We reviewed the clinicopathologic features, including age, sex, location, size, depth, lymphovascular invasion (LVI), LNM, ulceration, and intestinal metaplasia between the two groups in a large series of poorly cohesive, submucosa-invasive EGC (n = 317). RESULTS: LNM was found in 58 cases (18.3 %). Mixed SRC carcinoma histologic type (p < 0.001), larger tumor size (more than 2 cm) (p = 0.012), and the presence of LVI (p < 0.001) were associated with LNM. Pure SRC carcinomas accounted for 56.2 % (178/317) of the cases. Fourteen pure SRC carcinomas (7.8 %) showed LNM, whereas 44 mixed SRC carcinomas (31.9 %) exhibited LNM (p < 0.001). On multivariate logistic regression, the presence of LVI (odds ratio 6.737; 95 % confidence interval 2.714-16.720; p < 0.001) and mixed SRC carcinoma histologic type (odds ratio 4.674; 95 % confidence interval 2.370-9.216; p < 0.001) were independent predictors of LNM in poorly cohesive, submucosa-invasive EGC. CONCLUSIONS: The presence of a tubular component in SRC carcinoma was a risk factor for LNM in poorly cohesive, submucosa-invasive EGC. On the basis of this finding, we propose that the presence of a minor tubular component or the purity of the poorly cohesive/SRC carcinoma component should be reported in daily pathologic practice.
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Carcinoma de Células en Anillo de Sello/patología , Metástasis Linfática/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Femenino , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Males of many species fine-tune their ejaculates in response to sperm competition risk. Resource availability and the number of competitors during development can also strongly influence sperm production. However, despite the key role of seminal proteins in mediating reproductive processes, it is unclear whether seminal protein investment is dependent on the developmental environment.We manipulated the developmental environment of Drosophila melanogaster by rearing flies at low and high density. As expected, this resulted in large and small (i.e. high and low condition) adult phenotypes, respectively.As predicted, large males produced more of two key seminal proteins, sex peptide (SP) and ovulin, and were more successful at obtaining matings with both virgin and previously mated females. However, there was only a weak and non-significant trend for large males to transfer more absolute quantities of SP at mating, and thus, small males ejaculated proportionally more of their stored accessory gland SP resources.Males transferred more receptivity-inhibiting SP to large females. Despite this, large females remated more quickly than small females and thus responded to their developmental environment over and above the quantity of SP they received.The results are consistent with two non-mutually exclusive hypotheses. First, flies might respond to condition-dependent reproductive opportunities, with (i) small males investing heavily in ejaculates when mating opportunities arise and large males strategically partitioning SP resources and (ii) small females remating at reduced rates because they have higher mating costs or need to replenish sperm less often.Second, flies may be primed by their larval environment to deal with similar adult population densities, with (i) males perceiving high density as signalling increased competition, leading small males to invest proportionally more SP resources at mating and (ii) females perceiving high density as signalling abundant potential mates, leading to a higher sexual receptivity threshold.Thus, by influencing the mating frequencies of both sexes, as well as the quantity of seminal proteins produced by males and received by females, the developmental environment is likely to have far-reaching and sex-specific consequences for sexual selection and sexual conflict.