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BACKGROUND: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN. METHODS: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis. RESULTS: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13-4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel. CONCLUSIONS: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.
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A 72 year-old man was referred to our hospital for a detailed examination of a recurrent rectal polyp. He had past histories of surgery and radiation therapy for prostate cancer at the age of 66 and endoscopic excision of a rectal polyp at the age of 70. Colonoscopy revealed a semi-pedunculated lesion surrounded by friable mucosa, which was positive under positron-emission tomography-computed tomography. Histopathological examination of the endoscopically excised polyp revealed proliferation of atypical cells, characterized by strong pleomorphic or spindle morphology, which was immunohistochemically compatible with undifferentiated pleomorphic sarcoma. We diagnosed this case as sarcoma presumably associated with radiation proctitis.
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INTRODUCTION: There is considerable concern about whether endoscopic resection (ER) before additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, the aim of this study was to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER vs primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study. METHODS: This study investigated 6,105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis. RESULTS: After propensity score matching, 1,219 of 2,438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval: 0.49-1.08), indicating the noninferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the 2 groups (odds ratio: 1.34, 95% confidence interval: 0.76-2.40, P = 0.344). DISCUSSION: ER before AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.
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BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.
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Clasificación del Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Quimioradioterapia , Adulto , Estudios Retrospectivos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/mortalidad , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Anciano de 80 o más Años , Terapia Neoadyuvante , Tasa de Supervivencia , Curva ROC , Estudios de SeguimientoRESUMEN
Here, we report a rare case of a depressed lesion exhibiting both tubular differentiated adenocarcinomatous (TDA) and intraepithelial foveolar neoplasia (IFN) components (with the histological appearance of foveolar hyperplasia due to low-grade atypia). Histologically, the TDA surrounded the IFN, suggesting that the TDA may have originated from the IFN. Therefore, we examined molecular alterations in the TDA and IFN components separately. MUC5AC and MUC6 expression was observed immunohistochemically in both components. p53 expression was wild type in both components, suggesting no mutation of TP53. We investigated allelic imbalances at multiple loci (1p, 3p, 4p, 5q, 8q, 9p, 13q, TP53, 18q, and 22q), mutations (KRAS, BRAF, and GNAS), and DNA methylation and microsatellite status in both components using PCR-based analyses. Although multiple allelic imbalances were common to both components, allelic imbalances at 3p and TP53 were found only in the TDA component. No mutations were found, and DNA methylation status was low epigenotype for both components. Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Metilación de ADN/genética , Masculino , Mutación , Desequilibrio Alélico/genética , Mucina 5AC/genética , Mucina 5AC/metabolismo , Anciano , Femenino , Persona de Mediana EdadRESUMEN
Mutations in the TP53 gene, most commonly observed in colorectal cancer (CRC), play an essential role in colorectal carcinogenesis. Although p53 immunohistochemical (IHC) expression patterns have been argued to serve as an excellent surrogate marker for TP53 mutations, its performance has not been confirmed in CRC. We aimed to determine whether p53 IHC expression patterns accurately predict TP53 mutation status as examined by next-generation sequencing (NGS). We performed p53 IHC and sequencing of TP53 by NGS in 92 CRC cases with a microsatellite stable phenotype to investigate the correlation between TP53 mutation status and p53 IHC expression. The concordance between p53 IHC and TP53 mutation was 84/92 (91.3%) overall. However, 6 mutant cases were found in 39 cases with a wild-type IHC pattern. Additionally, there were two discordant cases in which an abnormal p53 IHC pattern (overexpression or cytoplasmic pattern) was found, while NGS detected wild-type p53. Therefore, the optimized p53 IHC performs well and serves as a surrogate test for TP53 mutation in CRC cases. Furthermore, it demonstrates excellent reproducibility between two independent experienced pathologists and may have novel clinical utility for molecular classification algorithms in CRC. We suggest that the four-tier classification of p53 IHC patterns is helpful to evaluate molecular colorectal carcinogenesis.
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We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array-based methods in 97 intestinal-type IMNs, including 39 low-grade dysplasias (LGDs), 37 high-grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.
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Variaciones en el Número de Copia de ADN , Neoplasias Gástricas , Humanos , Variaciones en el Número de Copia de ADN/genética , Estudio de Asociación del Genoma Completo , Mutación , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Inestabilidad CromosómicaRESUMEN
Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.
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BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.
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Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Humanos , Adenoma/genética , Adenoma/patología , Pólipos del Colon/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Hiperplasia , Osteonectina , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,259 patients with local resection alone [group A], 1,508 patients with additional surgery after local resection [group B], and 1,952 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,801 patients. The LNM incidence was 10.3% (95% confidence interval 9.3-11.4) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.2) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.2%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.
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BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.
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Adenocarcinoma , Endoscopía Capsular , Neoplasias Duodenales , Neoplasias del Íleon , Neoplasias Intestinales , Neoplasias del Yeyuno , Anciano , Humanos , Masculino , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/patología , Neoplasias del Íleon/diagnóstico , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/terapia , Japón/epidemiología , Neoplasias del Yeyuno/diagnóstico , PronósticoRESUMEN
PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Japón , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Intestino Delgado/patología , Irinotecán/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Oxaliplatino/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Data regarding the status of the vertical margin of sessile serrated lesions (SSLs) resected using cold snare polypectomy (CSP) are lacking, and whether a histopathologically positive vertical margin is related to recurrence remains unclear. Therefore, this preliminary study aimed to clarify the rates of positive or unassessable vertical and horizontal margins and the rate of muscularis mucosae resection in SSLs treated using CSP compared with those treated with EMR. METHODS: Histologic outcomes of patients treated with CSP or EMR for SSLs were evaluated in this single-center observational study. The primary outcome was the incidence of histopathologically positive vertical margins in CSP and EMR. Furthermore, the comparisons were adjusted for confounding factors using propensity score matching. RESULTS: Overall, 82 patients with SSLs were included in the CSP and EMR groups after matching. The incidence of positive histologic vertical margins in the CSP and EMR groups were 67.1% and 2.4%, respectively (P < .001). Regarding the evaluation of the presence of muscularis mucosae, 29.3% and 98.8% of patients in the CSP and EMR groups, respectively, had a complete muscularis mucosae resection (P < .001). CONCLUSIONS: A rigorous histopathologic evaluation revealed that for SSLs, CSP more frequently leads to positive vertical margins than EMR. (Clinical trial registration number: UMIN 000051569.).
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Pólipos del Colon , Resección Endoscópica de la Mucosa , Mucosa Intestinal , Márgenes de Escisión , Humanos , Masculino , Femenino , Resección Endoscópica de la Mucosa/métodos , Anciano , Persona de Mediana Edad , Pólipos del Colon/cirugía , Pólipos del Colon/patología , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Colonoscopía/métodos , Puntaje de PropensiónRESUMEN
Recent studies have shown that sessile serrated lesions (SSLs) lead to the development of colorectal cancer (CRC) with a microsatellite instability (MSI) phenotype via a dysplasia-carcinoma sequence. However, the pathological and molecular mechanisms of SSL with dysplasia (SSLD) are unclear. Here, we aimed to examine the clinicopathological and molecular alterations in SSLD and to evaluate the significance of such alterations with regard to lesion progression. Fifty-four SSLDs (20 serrated dysplasia cases and 17 intestinal dysplasia cases, including 30 low-grade dysplasia [LGD] cases, 7 high-grade dysplasia [HGD] cases, and 17 intramucosal adenocarcinomas [IMAs]) were evaluated. Molecular alterations, including immunohistochemical expression of various markers, DNA methylation status, and multiple genetic mutations (using next-generation sequencing), were assessed. Additionally, such alterations were also investigated in 41 CRCs with an MSI phenotype (invasion beyond submucosa). The frequency of mismatch repair (MMR) deficiency in SSLD was 12 of 39 cases (32.4 %), whereas the MMR proficient type was observed in 17 of 39 SSLD cases. SSLD with serrated dysplasia showed a significantly higher frequency of loss of MMR protein expression and methylation status. Moreover, loss of MMR protein expression differed significantly between LGD and IMA. Furthermore, the frequency of TP53 mutation was significantly higher in IMA than in LGD. The current findings demonstrated that SSL with serrated dysplasia may be associated with an increased risk of malignant transformation compared with intestinal dysplasia. Loss of MMR proteins and mutation of TP53 may play important roles in tumor progression from dysplasia to carcinomatous lesions.
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Adenocarcinoma , Adenoma , Neoplasias Encefálicas , Pólipos del Colon , Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Humanos , Inestabilidad de Microsatélites , Neoplasias Colorrectales/patología , Adenoma/genética , Adenoma/patología , Hiperplasia , Adenocarcinoma/genética , Adenocarcinoma/patología , Fenotipo , Mutación , Pólipos del Colon/genética , Pólipos del Colon/patología , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3+CD4+FoxP3+ cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response.
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Linfocitos T Reguladores , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Anciano , Femenino , Linfocitos T Reguladores/patología , Estudios Retrospectivos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patología , Cistectomía , Respuesta Patológica Completa , Inmunidad , Músculos/patología , Invasividad Neoplásica/patología , Microambiente TumoralRESUMEN
BACKGROUND: Tumor-associated macrophages (TAMs) are an immune component of the cutaneous malignant melanoma (CMM) microenvironment and affect tumor growth. TAMs can polarize into different phenotypes, that is, proinflammatory M1 and anti-inflammatory M2 macrophages. However, the role of the macrophage phenotype in CMM remains unclear. METHODS: We examined 88 patients with CMM. Tissue microarrays were constructed, and the density of M1 and M2 macrophages was analyzed by immunohistochemistry. Immune cells coexpressing CD68 and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were considered M1 macrophages, whereas those coexpressing CD68 and c-macrophage activating factor (c-Maf) were defined as M2 macrophages. These TAMs were counted, and the relationships between the density of M1 and M2 macrophages and clinicopathological factors including prognosis were investigated. RESULTS: The CD68/c-Maf score ranged from 0 to 34 (median: 5.5). The patients were divided based on the median score into the CD68/c-Maf high (≥5.5) and low (<5.5) expression groups. Univariate and multivariate analyses revealed that CD68/c-Maf expression was an independent predictive factor for progression-free survival and an independent prognostic factor for overall survival. CD68/pSTAT1 expression was found in only two patients. CONCLUSION: We suggest that CD68/pSTAT1 coexpression is rarely observed in patients with CMM, and high CD68/c-Maf expression is a predictor of worse prognosis in these patients.
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Melanoma , Neoplasias Cutáneas , Humanos , Melanoma Cutáneo Maligno , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Antígenos CD/metabolismo , Melanoma/metabolismo , Neoplasias Cutáneas/patología , Pronóstico , Microambiente Tumoral , Antígenos de Diferenciación Mielomonocítica/metabolismoRESUMEN
OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Pronóstico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Neoplasias del Colon/patología , Resultado del Tratamiento , Estadificación de NeoplasiasRESUMEN
BACKGROUND: It has been suggested that serum leucine-rich α-2 glycoprotein (LRG) could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease. In particular, the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis (UC) has become a matter of interest. AIM: To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC. METHODS: This was a cross-sectional, single-center, observational study of Japanese patients with UC. Among 213 patients with UC, in whom LRG was measured from September 2020 to February 2022, we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein (CRP) were performed on the same day. We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices, including the Mayo endoscopic subscore and UC endoscopic index of severity. RESULTS: Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant (r = 0.754, P < 0.0001; r = 0.778, P < 0.0001, respectively). There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity (r = 0.599, P = 0.0005; r = 0.563, P = 0.0012, respectively), although the correlation coefficients were higher for LRG. The LRG cut-off value for predicting endoscopic remission was 13.4 µg/mL for a Mayo endoscopic subscore of 0 [area under the curve (AUC): 0.871; 95% confidence interval (CI): 0.744-0.998], and 13.4 µg/mL for an UC endoscopic index of severity of 0 or 1 (AUC: 0.904; 95%CI: 0.792-1.000). CONCLUSION: LRG may be a surrogate marker for endoscopic activity in UC, with a cut-off value of around 13.4 µg/mL for endoscopically inactive disease.