RESUMEN
OBJECTIVES: An investigation of patients with pancreatic carcinoma aims to identify those who will benefit from surgery. Physical examination, radiology and laboratory findings are helpful. Most prognostic markers, such as lymph node status, micro metastasis and tumour differentiation, are not preoperatively accessible. Metastatic disease in lymph node 8a (Ln8a) in patients operated for pancreatic carcinoma has been reported to be a predictor of shorter overall survival (OS). This lymph node can be assessed preoperatively through resection (possibly even with laparoscopy) and subsequent histopathology. The value of the procedure is disputed. The aim of this study is to investigate whether metastatic disease in Ln8a is a predictor of decreased OS. MATERIALS AND METHODS: In patients with suspected pancreatic or periampullary carcinoma, who were operated with pancreatoduodenectomy (PD), Ln8a was separately resected and analysed with standard and immuno-histochemical methods. Patients with or without metastasis in Ln8a were compared regarding OS. RESULTS: Between 2008 and 2011, 122 consecutive patients were eligible and 87 were resected and had LN8a analysed separately. Sixteen patients were Ln8a + and 71 were Ln8a-. Patients with Ln8a + had a significantly reduced median OS as compared to patients with Ln8a- (0.74 (95% CI 0.26-1.26) versus 5.91 years (95% CI 2.91-), p < .001). CONCLUSION: Ln8a + was associated with a marked reduction of OS, indicating a possible role in the future preoperative workup in patients with a suspicion of pancreatic cancer.
Asunto(s)
Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Ganglio Linfático Centinela/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Páncreas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Suecia , Centros de Atención TerciariaRESUMEN
OBJECTIVE: Patients who undergo ileal pouch-anal anastomosis (IPAA) after colectomy for ulcerative colitis (UC) occasionally have neoplasia in the IPAA. Patients with evidence of dysplasia or carcinoma in the colorectal specimen may have an increased risk of such neoplasia. A surveillance program has been suggested. The aims of this study were to evaluate the outcomes of surveillance of a large patient cohort, and to investigate the prevalences of neoplasia in the ileal pouch mucosa and in the anal transitional zone (ATZ). MATERIAL AND METHODS: A total of 629 patients underwent IPAA for UC at Sahlgrenska University Hospital, Gothenburg, Sweden. Identified from a register, 73 patients with neoplasia in their specimen considered eligible for the trial were prospectively enrolled, and underwent clinical examination, endoscopy with macroscopic evaluation, and mucosal biopsies from the ileal pouch and the ATZ. The biopsies were independently evaluated by two experienced gastro-pathologists. RESULTS: In all, 56 patients (39 males) with a median follow-up time of 18 (range, 1-29) years were evaluated. One patient (1.8%; 95% CI 0%-5.3%) showed low-grade dysplasia in the pouch, as recorded by one of the two pathologists. The individual pathologists recorded indefinite for dysplasia (IFD) in the pouch for 19 and 20 patients, respectively, and IFD in the ATZ for 2 and 4 patients, respectively. None of the biopsies showed evidence of high-grade dysplasia (HGD) or carcinoma. CONCLUSIONS: Neoplasia in the ileal pouch or ATZ after IPAA for UC is rare in the proposed risk group. The necessity for and value of a routine surveillance program should be prospectively evaluated.
Asunto(s)
Anastomosis Quirúrgica/efectos adversos , Carcinoma/patología , Colitis Ulcerosa/patología , Reservorios Cólicos/patología , Proctocolectomía Restauradora/efectos adversos , Adulto , Anciano , Canal Anal/patología , Biopsia , Colitis Ulcerosa/cirugía , Femenino , Estudios de Seguimiento , Humanos , Íleon/patología , Masculino , Persona de Mediana Edad , Factores de Riesgo , SueciaRESUMEN
Tumor progression in the colon moves from aberrant crypt foci to adenomatous polyps to invasive carcinomas. The composition of the tumor-infiltrating leukocyte population affects the ability of the immune system to fight the tumor. T cell infiltration into colorectal adenocarcinomas, particularly T helper 1 (Th1) type T cells as well as increased regulatory T cell (Treg) frequencies, is correlated with improved prognosis. However, whether Th1 cells and Tregs are already present at the adenoma stage is not known. In this study, the APC(Min/+) mouse model of intestinal adenomatous polyposis was used to investigate tumor-associated lymphocyte subsets and the mechanisms of their accumulation into gastrointestinal adenomas. Compared to unaffected tissue, adenomas accumulated CD4(+)FoxP3(+) putative Treg in parallel with lower frequencies of conventional T cells and B cells. The accumulation of Treg was also observed in human adenomatous polyps. Despite high Treg numbers, the function of conventional T cells present in the APC(Min/+) adenomas was not different from those in the unaffected tissue. Adenomas displayed an altered chemokine balance, with higher CCL17 and lower CXCL11 and CCL25 expression than in the unaffected tissue. In parallel, CXCR3(+) Tregs were largely absent from adenomas. The data indicate that already in early stages of tumor development, the balance of lymphocyte-recruiting chemokines is altered possibly contributing to the observed shift toward higher frequencies of Treg.
Asunto(s)
Adenocarcinoma/inmunología , Adenoma/inmunología , Quimiocinas/biosíntesis , Neoplasias Colorrectales/inmunología , Linfocitos T Reguladores/inmunología , Anciano , Animales , Quimiocinas/inmunología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana EdadRESUMEN
Breast cancer (BC) is a genetically heterogeneous disease with high prevalence in Northern Europe. However, there has been no detailed investigation into the Scandinavian somatic landscape. Here, in a homogeneous Swedish cohort, we describe the somatic events underlying BC, leveraging a targeted next-generation sequencing approach. We designed a 20.5 Mb array targeting coding and regulatory regions of genes with a known role in BC (n = 765). The selected genes were either from human BC studies (n = 294) or from within canine mammary tumor associated regions (n = 471). A set of predominantly estrogen receptor positive tumors (ER + 85%) and their normal tissue counterparts (n = 61) were sequenced to ~ 140 × and 85 × mean target coverage, respectively. MuTect2 and VarScan2 were employed to detect single nucleotide variants (SNVs) and copy number aberrations (CNAs), while MutSigCV (SNVs) and GISTIC (CNAs) algorithms estimated the significance of recurrent somatic events. The significantly mutated genes (q ≤ 0.01) were PIK3CA (28% of patients), TP53 (21%) and CDH1 (11%). However, histone modifying genes contained the largest number of variants (KMT2C and ARID1A, together 28%). Mutations in KMT2C were mutually exclusive with PI3KCA mutations (p ≤ 0. 001) and half of these affect the formation of a functional PHD domain. The tumor suppressor CDK10 was deleted in 80% of the cohort while the oncogene MDM4 was amplified. Mutational signature analyses pointed towards APOBEC deaminase activity (COSMIC signature 2) and DNA mismatch repair (COSMIC signature 6). We noticed two significantly distinct patterns related to patient age; TP53 being more mutated in the younger group (29% vs 9% of patients) and CDH23 mutations were absent from the older group. The increased somatic mutation prevalence in the histone modifying genes KMT2C and ARID1A distinguishes the Swedish cohort from previous studies. KMT2C regulates enhancer activation and assists tumor proliferation in a hormone-rich environment, possibly pointing to a role in ER + BC, especially in older cases. Finally, age of onset appears to affect the mutational landscape suggesting that a larger age-diverse population incorporating more molecular subtypes should be studied to elucidate the underlying mechanisms.