Iliac-hepatic arterial bypass for compromised collateral flow during modified Appleby operation for advanced pancreatic cancer

Involvement of the celiac trunk and common hepatic artery are two of the most common forms of vascular invasion by tumours of the distal pancreas, and until recently this finding was considered a contra-indication to resection. We described a modified Appleby operation for locally advanced distal pancreatic cancer with compromised hepatic collateral flow that needed hepatic arterial revascularization, successfully accomplished by left external iliac-hepatic arterial bypass with Dacron prosthesis. Patient recovery was uneventful and he was discharged on the 10th postoperative day. Postoperative angio-CT disclosed a patent arterial bypass. Patient is well and asymptomatic 13 months after operation. At the time of this writing, postoperative CT scan showed no evidence of disease and CA 19-9 level is normal. There is a well established rationale to perform extended resection of pancreatic carcinomas that compromise vascular structures. Modified Appleby procedure can safely be performed, has oncological advantages to palliative procedures and provides relief of pain but is reserved for selected patients. Preservation of hepatic arterial flow has utmost importance to avoid hepatobiliary complications as liver necrosis, liver abscess, gallbladder necrosis or cholecystitis. In this case, hepatic revascularization was particularly challenging, but was successfully accomplished by left external iliac-hepatic arterial bypass. To our knowledge this type of arterial bypass has never been described so far in the English literature and its description may be important for surgeons dealing with advanced pancreatic cancer. (C) 2009 Elsevier Ltd. All rights reserved.

Analysis of outcome and cancer stem cells status in patients with resectable pancreatic adenocarcinoma

RESUMO: Actualmente, a única possibilidade de cura para doentes com adenocarcinoma do pâncreas (PDAC) é a ressecção cirúrgica, no início deste estudo, perguntamo-nos se os predictores clínico-patológicos clássicos de prognostico poderiam ser validados em uma grande cohort de doentes com cancro do pâncreas ressecável e se outros predictores clínicos poderiam ter um papel na decisão de que doentes beneficiariam de ressecção cirúrgica. No capítulo 2, observamos que até 30% dos doentes morrem no primeiro ano após a ressecção cirúrgica, pelo que o nosso objectivo foi determinar factores pré-operatórios que se correlacionam com mortalidade precoce após ressecação cirúrgica com recurso a um instrumento estatisticamente validado, o Charlson-Age Comorbidity Index (CACI), determinamos que um CACI score superior a 4 foi preditivo de internamentos prolongados (p <0,001), complicações pós-operatórias (p = 0,042), e mortalidade em 1 ano pós- ressecção cirúrgica (p <0,001). Um CACI superior a 6 triplicou a mortalidade no primeiro ano pós-cirurgia e estes doentes têm menos de 50% de probabilidade de estarem vivos um ano após a cirurgia. No capítulo 3, o nosso objectivo foi identificar uma proteína de superfície que se correlacionasse estatisticamente com o prognostico de doentes com adenocarcinoma do pâncreas e permitisse a distinção de subgrupos de doentes de acordo com as suas diferenças moleculares, perguntamo-nos ainda se essa proteína poderia ser um marcador de células-estaminais. No nosso trabalho anterior observamos que as células tumorais na circulação sanguínea apresentavam genes com características bifenotípica epitelial e mesenquimal, enriquecimento para genes de células estaminais (ALDH1A1 / ALDH1A2 e KLF4), e uma super-expressão de genes da matriz extracelular (colagénios, SPARC, e DCN) normalmente identificados no estroma de PDAC. Após a avaliação dos tumores primários com RNA-ISH, muitos dos genes identificados, foram encontrados co-localizando em uma sub-população de células na região basal dos ductos pancreáticos malignos. Além disso, observamos que estas células expressam o marcador SV2A neuroendócrino, e o marcador de células estaminais ALDH1A1/2. Em comparação com tumores negativos para SV2, os doentes com tumores SV2 positivos apresentaram níveis mais baixos de CA 19-9 (69% vs. 52%, p = 0,012), tumores maiores (> 4 cm, 23% vs. 10%, p = 0,0430), menor invasão de gânglios linfáticos (69% vs. 86%, p = 0,005) e tumores mais diferenciados (69% vs. 57%, p = 0,047). A presença de SV2A foi associada com uma sobrevida livre de doença mais longa (HR: 0,49 p = 0,009) bem como melhor sobrevida global (HR: 0,54 p = 0,018). Em conjunto, esta informação aponta para dois subtipos diferentes de adenocarcinoma do pâncreas, e estes subtipos co-relacionam estatisticamente com o prognostico de doentes, sendo este subgrupo definido pela presença do clone celular SV2A / ALDH1A1/2 positivo com características neuroendócrinas. No Capítulo 4, a expressão de SV2A no cancro do pâncreas foi validado em linhas celulares primárias. Demonstramos a heterogeneidade do adenocarcinoma do pâncreas de acordo com características clonais neuroendócrinas. Ao comparar as linhas celulares expressando SV2 com linhas celulares negativas, verificamos que as linhas celulares SV2+ eram mais diferenciadas, diferindo de linhas celulares SV2 negativas no que respeita a mutação KRAS, proliferação e a resposta à quimioterapia. No capítulo 5, perguntamo-nos se o clone celular SV2 positivo poderia explicar a resistência a quimioterapia observada em doentes. Observamos um aumento absoluto de clones celulares expressando SV2A, em múltiplas linhas de evidência - doentes, linhas de células primárias e xenotransplantes. Embora, tenhamos sido capazes de demonstrar que o adenocarcinoma do pâncreas é uma doença heterogénea, consideramos que a caracterização genética destes clones celulares expressando SV2A é de elevada importância. Pretendemos colmatar esta limitação com as seguintes estratégias: Após o tratamento com quimioterapia neoadjuvante na nossa coorte, realizamos microdissecação a laser das amostras primarias em parafina, de forma a analisar mutações genéticas observadas no adenocarcinoma pancreático; em segundo lugar, pretendemos determinar consequências de knockdown da expressão de SV2A em nossas linhas celulares seguindo-se o tratamento com gemicitabina para determinação do papel funcional de SV2A; finalmente, uma vez que os nossos esforços anteriores com um promotor - repórter e SmartFlare ™ falharam, o próximo passo será realizar RNA-ISH PrimeFlow™ seguido de FACS e RNA-seq para caracterização deste clone celular. Em conjunto, conseguimos provar com várias linhas de evidência, que o adenocarcinoma pancreático é uma doença heterogénea, definido por um clone de células que expressam SV2A, com características neuroendócrinas. A presença deste clone no tecido de doentes correlaciona-se estatisticamente com o prognostico da doença, incluindo sobrevida livre de doença e sobrevida global. Juntamente com padrões de proliferação e co-expressão de ALDH1A1/2, este clone parece apresentar um comportamento de células estaminais e está associado a resistência a quimioterapia, uma vez que a sua expressão aumenta após agressão química, quer em doentes, quer em linhas de células primárias.----------------------------- ABSTRACT: Currently, the only chance of cure for patients with pancreatic adenocarcinoma is surgical resection, at the beginning of my thesis studies, we asked if the classical clinicopathologic predictors of outcome could be validated in a large cohort of patients with early stage pancreatic cancer and if other clinical predictors could have a role on deciding which patients would benefit from surgery. In chapter 2, we found that up to 30% of patients die within the first year after curative intent surgery for pancreatic adenocarcinoma. We aimed at determining pre-operative factors that would correlate with early mortality following resection for pancreatic cancer using a statistically validated tool, the Charlson-Age Comorbidity Index (CACI). We found that a CACI score greater than 4 was predictive of increased length of stay (p<0.001), post-operative complications (p=0.042), and mortality within 1-year of pancreatic resection (p<0.001). A CACI score of 6 or greater increased 3-fold the odds of death within the first year. Patients with a high CACI score have less than 50% likelihood of being alive 1 year after surgery. In chapter 3 we aimed at identifying a surface protein that correlates with patient’s outcome and distinguishes sub-groups of patients according to their molecular differences and if this protein could be a cancer stem cell marker. The most abundant class of circulating tumor cells identified in our previous work was found to have biphenotypic features of epithelial to mesenchymal transition, enrichment for stem-cell associated genes (ALDH1A1/ALDH1A2 and KLF4), and an overexpression of extracellular matrix genes (Collagens, SPARC, and DCN) normally found in the stromal microenvironment of PDAC primary tumors. Upon evaluation of matched primary tumors with RNA-ISH, many of the genes identified were found to co-localize in a sub-population of cells at the basal region of malignant pancreatic ducts. In addition, these cells expressed the neuroendocrine marker SV2A, and the stem cell marker ALDH1A1/2. Compared to SV2 negative tumors, patients with SV2 positive tumors were more likely to present with lower CA 19-9 (69% vs. 52%, p = 0.012), bigger tumors (size > 4 cm, 23% vs. 10%, p= 0.0430), less nodal involvement (69% vs. 86%, p = 0.005) and lower histologic grade (69% vs. 57%, p = 0.047). The presence of SV2A expressing cells was associated with an improved disease free survival (HR: 0.49 p=0.009) and overall survival (HR: 0.54 p=0.018) and correlated linearly with ALDH1A2. Together, this information points to two different sub-types of pancreatic adenocarcinoma, and these sub-types correlated with patients’ outcome and were defined by the presence of a SV2A/ ALDH1A1/2 expressing clone with neuroendocrine features. In Chapter 4, SV2A expression in cancer was validated in primary cell lines. We were able to demonstrate pancreatic adenocarcinoma heterogeneity according to neuroendocrine clonal features. When comparing SV2 expressing cell lines with SV2 negative cell lines, we found that SV2+ cell lines were more differentiated and differ from SV2 negative cell lines regarding KRAS mutation, proliferation and response to chemotherapy. In Chapter 5 we aimed at determining if this SV2 positive clone could explain chemoresistance observed in patients. We found an absolute increase in SV2A expressing cells, with multiple lines of evidence, in patients, primary cell lines and xenografts. Although, we have been able to show evidence that pancreatic adenocarcinoma is a heterogeneous disease, our findings warrant further investigation. To further characterize SV2A expressing clones after treatment with neoadjuvant chemotherapy in our cohort, we have performed laser capture microdissection of the paraffin embedded tissue in this study and will analyze the tissue for known genetic mutations in pancreatic adenocarcinoma; secondly, we want to know what will happen after knocking down SV2A expression in our cell lines followed by treatment with gemcitabine to determine if SV2A is functionally important; finally, since our previous efforts with a promoter – reporter and SmartFlare™ have failed, we will utilize a novel PrimeFlow™ RNA-ISH assay followed by FACS and RNA sequencing to further characterize this cellular clone. Overall our data proves, with multiple lines of evidence, that pancreatic adenocarcinoma is a heterogeneous disease, defined by a clone of SV2A expressing cells, with neuroendocrine features. The presence of this clone in patients’ tissue correlates with patient’s disease free survival and overall survival. Together with patterns of proliferation and ALDH1A1/2 co-expression, this clone seems to present a stem-cell-like behavior and is associated with chemoresistance, since it increases after chemotherapy, both in patients and primary cell lines.

How Much Chemotherapy Are Patients With Advanced Pancreatic Cancer Receiving at the End of Life?

Background: Advanced pancreatic adenocarcinoma (APC) is a chemoresistant cancer with poor prognosis. We evaluated the use of chemotherapy in the last months of life.Methods: Retrospective analysis of patients with APC treated from 1993 to 2010 at the Oncology Institute of Southern Switzerland. Clinical and laboratory parameters starting from 28 days prior to the last administration of chemotherapy were recorded, including ECOG performance status, presence of ascites, haemoglobin (Hb), white blood cell (WBC) count, platelets, total bilirubin, albumin, LDH, C-reactive protein (C-rp) and Ca 19.9.Results: The characteristics of the 231 patients were: males/females 53%/47%; metastatic/locally advanced disease 80%/20%; median age 66 years (range 32−85). Median overall survival calculated from diagnosis was 6.1 months (95% CI: 5.1−7.2); death was due to disease progression in all cases. At last chemotherapy administration, ECOG performance status was 0−1 in 38% and 2−3 in 62%. Fifty-nine percent of pts received first-line chemotherapy only (gemcitabine in 70%; gemcitabine-based doublets or 5FU in 30%), whilst 32%, 8% and 1% had second- (5FU 37%; oxaliplatinbased doublets 57%; phase I trial 6%), third- and fourth-line therapy (single agent or phase I trial), respectively. The interval between last chemotherapy administration and death was <4 weeks in 24%, _4−12 weeks in 47% and >12 weeks in 29%. Table 1 summarizes the proportion of patients treated according to the interval between last chemotherapy and death refered to chemotherapy line. Median survival from last chemotherapy delivery to death was 7.5 weeks (95% CI 6.7−8.4). In univariate analysis, presence of ascites, elevated WBC, total bilirubin, LDH, C-rp and Ca 19.9, and reduced albumin were found to predict shorter survival (p < 0.05 for each). However, none of them was an independent predictor in the multivariate analysis.Conclusions: A significant proportion of patients with APC received chemotherapy in the last months of life. In our study, none of the clinical and laboratory parameters recorded 28 days priorto the last chemotherapy delivery were found to predict survival.

Chemotherapy in patients with advanced pancreatic cancer: too close to death?

PURPOSE: We evaluated the attitude in using chemotherapy near the end of life in advanced pancreatic adenocarcinoma (PAC). Clinical and laboratory parameters recorded at last chemotherapy administration were analyzed, in order to identify risk factors for imminent death. METHODS: Retrospective analysis of patients who underwent at least one line of palliative chemotherapy was made. Data concerning chemotherapy (regimens, lines, and date of last administration) were collected. Clinical and laboratory factors recorded at last chemotherapy administration were: performance status, presence of ascites, hemoglobin, white blood cell (WBC), platelets, total bilirubin, albumin, LDH, C-reactive protein (C-rp), and Ca 19.9. RESULTS: We analyzed 231 patients: males/females, 53/47 %; metastatic/locally advanced disease, 80/20 %; and median age, 66 years (range 32-85). All patients died due to disease progression. Median overall survival was 6.1 months (95 % CI 5.1-7.2). At the last chemotherapy delivery, performance status was 0-1 in 37 % and 2 in 63 %. Fifty-nine percent of patients received one chemotherapy line, while 32, 8, and 1 % had second-, third-, and fourth line, respectively. The interval between last chemotherapy administration and death was <4 weeks in 24 %, ≥4-12 in 47 %, and >12 in 29 %. Median survival from last chemotherapy to death was 7.5 weeks (95 % CI 6.7-8.4). In a univariate analysis, ascites, elevated WBC, bilirubin, LDH, C-rp and Ca 19.9, and reduced albumin were found to predict shorter survival; however, none of them remained significant in a multivariate analysis. CONCLUSIONS: A significant proportion of patients with advanced PAC received chemotherapy within the last month of life. The clinical and laboratory parameters recorded at last chemotherapy delivery did not predict shorter survival.

Quimioterapia neoadjuvante torna ressecável carcinoma de cabeça de pâncreas

We present a case of non-resectable head pancreatic cancer by mesenteric venous invasion in which treatment with Gemcitabine (Gemzar) 1.000 mg/m 2 weekly for 3 weeks, followed by a 1-week rest, normalized CA 19.9 and promoted tumor resecability in a second operation (ultrasound, helicoidal tomography and magnetic ressonance exams). The value of the adjuvant treatment (radiochemotherapy) and the association with immunotherapy (Interferon) is discussed.

Avaliação hormonal e de marcadores séricos em pacientes com abortamento

Estudos têm demonstrado a utilização de glicoproteínas e hormônios para prognosticar a evolução de uma gravidez complicada por ameaça de abortamento. Entretanto, alguns resultados ainda são duvidosos. Portanto, o objetivo deste estudo foi avaliar as dosagens de CA-125, CA-19.9, CA-15.3, beta-hCG, estradiol, progesterona, alfa-fetoproteína e antígeno cárcino-embrionário no sangue periférico de mulheres com abortamento inevitável (n=18) e com ameaça de abortamento que posteriormente evoluíram para o abortamento (n=6) no prazo de 1 a 26 dias. O grupo controle foi constituído de mulheres grávidas normais com idade gestacional semelhante (n=7). Todas as pacientes foram atendidas no Hospital Escola e/ou Ambulatório de Ginecologia e Obstetrícia da Faculdade de Medicina do Triângulo Mineiro. Os resultados demonstraram que as dosagens de CA-125 nos grupos controle, abortamento inevitável e ameaça de abortamento foram, respectivamente: 24,7 ± 13,4 UI/ml; 153,9 ± 43,3 UI/ml e 17,4 ± 2,6 UI/ml sendo estatisticamente significante a diferença entre o grupo com abortamento inevitável em comparação com os outros grupos. A dosagem de CA-19.9 foi significantemente menor no grupo com abortamento inevitável em relação ao grupo com ameaça de abortamento (6,6 ± 1,4 UI/ml versus 20,2 ± 11,4 UI/ml). A dosagem de estradiol foi significantemente menor no grupo com abortamento inevitável em comparação com o grupo controle (1.327 ± 1.015 ng/ml versus 10.774 ± 9.244 ng/ml). As pacientes com ameaça de abortamento e com abortamento inevitável apresentaram níveis mais baixos de progesterona que o grupo controle, respectivamente: 17,38 ± 9,4 ng/ml; 18,3 ± 8,9 ng/ml e 60,4 ± 26,8 ng/ml. Concluímos que as dosagens de progesterona, CA-19.9 e do beta-hCG podem servir como prognóstico de evolução de uma gravidez inicial complicada com ameaça de abortamento.

Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma

Metabolomics as one of the most rapidly growing technologies in the "-omics" field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Formula: see text] We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and-despite all its current limitations-can deliver marker panels with high selectivity even in multi-class settings.

Retrospective cohort study to determine the effect of metformin on survival of diabetic patients with pancreatic adenocarcinoma

Background: Pancreatic cancer is the fourth most common cause of cancer death in the United States. Despite advances in cancer treatment, prognosis of pancreatic cancer remains extremely poor with survival rates of 24% and 5% in 1 and 5 years, respectively. Many patients with pancreatic cancer have a history of diabetes and are treated with various antidiabetic regimens including metformin. In multiple retrospective studies, metformin has been associated with decreased risk of cancer and cancer-related mortality. Metformin has also been reported to inhibit the growth of cancer cells, both in vitro and in vivo.^ Methods: We conducted a retrospective cohort study to examine the survival benefit of metformin in diabetic patients with pancreatic cancer at MD Anderson Cancer Center (MDACC). A dataset of 397 patients who carried the diagnosis of "Diabetes Mellitus" and "Pancreatic Cancer" at MD Anderson were screened for this study. ^ Results: Mean age of patients at diagnosis of cancer was 64.0 ± 8.7 years (range 37-84). The majority of the patients were male (65.6%) and of Caucasian race (78.5%). The most common antidiabetic regimen used were insulin and metformin (in 39.1% and 38.7%, respectively). Patients' cancer were staged as resectable in 34.1%, locally advanced unresectable in 29.1%, and disseminated disease in 36.7% of cases. Overall 1-year and 3-year survival rates for all stages combined were 51.8% and 7.6%, respectively. Earlier stage, metformin use, low CA19-9 level, better ECOG performance status, surgical intervention, negative surgical margins, and smaller tumor size were associated with longer survival. Metformin use was associated with a 33% decrease in risk of death (HR: 0.67; 95% CI: 0.51-0.88). Multivariate Cox proportional hazard regression showed hazard ratio of 1.77 (95% CI 1.49-2.10) for cancer stage, 0.65 (95% CI 0.49-0.86) for metformin use, and 1.68 (95% CI 1.26-2.23) for CA 19-9 level above population median. ^ Conclusion: Our study suggests that metformin may improve the outcome in diabetic patients with pancreatic cancer independently of other known prognostic factors. Pancreatic cancer carries extremely poor prognosis; metformin may provide a suitable adjunct therapeutic option for pancreatic cancer in patients with and without diabetes mellitus.^

Correlation of blood type with thrombosis in pancreatic cancer patients

Objective: The study aimed to identify the risk factors involved in initiating thromboembolism (TE) in pancreatic cancer (PC) patients, with focus on ABO blood type. ^ Methods and Patients: There were 35.7% confirmed cases of TE and 64.3% cases remained free of TE (n=687). There were 12.7% only Pulmonary embolism (PE), 9% only Deep vein thrombosis (DVT), 53.5% only other sites, 3.3% combined PE and DVT, 8.6% combined PE and other sites, 9.8% combined DVT and other sites, and 3.3% all three combined cases. ^ Results: The risk factors for thrombosis identified by multivariate logistic regression were: history of previous anti-thrombotic treatment, tumor site in pancreatic body or tail, large tumor size, maximum glucose category more than 126 and 200 mg/dL. ^ The factors with worse overall survival by multivariate Cox regression and Kaplan Meier analyses were: locally advanced or metastatic stage, worsening performance status, high CA 19-9 levels, and HbA1C levels more than 6 %, at diagnosis. ^ There were 29.1% and 39.1% of the patients with thrombosis in the O and non-O blood type groups respectively. Both Non-O blood type (P=0.02) and the A, B and AB blood types (P= 0.007) were associated with thrombosis as compared to O type. The odds of thrombosis were nearly half in O blood type patients as compared to non-O blood type [OR-0.54 (95% C.I.- 0.37-0.79), P<0.001]. ^ Conclusion: A better understanding of the TE and PC relationship and involved risk factors may provide insights on tumor biology and patient response to prophylactic anticoagulation therapy.^

Avaliação dos biomarcadores urinários no controle do tratamento de estenose de junção ureteropélvica em adultos

INTRODUÇÃO E OBJETIVO: A estenose de junção ureteropélvica (EJUP) é importante causa de obstrução do trato urinário e pode levar a deterioração progressiva da função renal. Há espaço para o aprimoramento de novos métodos diagnósticos capazes de discriminar hidronefrose e uropatia obstrutiva. Acredita-se que os biomarcadores urinários podem fornecer indícios de lesão renal precoce na obstrução urinária. Neste contexto, KIM-1 pode elevar-se na urina por lesão tubular proximal, NGAL por lesão no túbulo proximal, distal ou alça de Henle, CA19-9 por produção excessiva no túbulo obstruído e ?2-microglobulina (beta2M) por injúria ao glomérulo ou ao túbulo proximal. O objetivo do presente estudo foi avaliar as propriedades diagnósticas dos biomarcadores urinários citados em adultos com EJUP, sendo o primeiro estudo na literatura a avaliar tais moléculas nesta população. MÉTODOS: Foram estudados de modo prospectivo pacientes consecutivos acima de 18 anos com diagnóstico de EJUP submetidos a pieloplastia videolaparoscópica de dezembro de 2013 a fevereiro de 2015. Foram excluídos do estudo pacientes com EJUP bilateral, rim contralateral patológico, EJUP em rim único, antecedentes de tratamento cirúrgico para estenose de JUP ou taxa de filtração glomerular inferior a 60 ml/min/1,73m2. Cada paciente forneceu quatro amostras de urina para medição de biomarcadores, uma no pré-operatório e outras com 1, 3 e 6 meses de seguimento pós-operatório. O grupo controle foi constituído por voluntários saudáveis sem hidronefrose à ultrassonografia. RESULTADOS: Foram incluídos 47 pacientes com idade média de 38,6 ± 12,7 anos (intervalo 19 a 64 anos), sendo 17 (36,2%) do sexo masculino e 30 (62,8%) do sexo feminino. O grupo controle foi composto por 40 indivíduos semelhantes ao grupo com EJUP no que concerne idade (p = 0,95) e sexo (p = 0,82). KIM-1 foi o marcador com melhores propriedades diagnósticas, apresentando área sob a curva (AUC) de 0,79 (95% CI 0,70 a 0,89). O NGAL, por sua vez, teve AUC de 0,71 (95% CI 0,61 a 0,83), CA19- 9 teve AUC de 0,70 (95% CI 0,60 a 0,81) e (beta2M) apresentou AUC de 0,61 (95% CI 0,50 a 0,73), sendo o único biomarcador com propriedades inadequadas neste cenário. O KIM-1 foi o marcador mais sensível com o ponto de corte 170,4 pg/mg de creatinina (sensibilidade 91,4%, especificidade 59,1%) e o CA 19-9 o mais específico para o ponto de corte de 51,3 U/mg de creatinina (sensibilidade 48,9%, especificidade 88,0%), enquanto o NGAL foi o que apresentou maior queda após desobstrução, com 90,0% dos pacientes apresentando clareamento superior a 50%. CONCLUSÕES: A avaliação dos biomarcadores urinários é útil no diagnóstico de obstrução em adultos com EJUP submetidos a pieloplastia videolaparoscópica. O KIM-1 foi o marcador mais sensível e o CA 19-9 o mais específico, enquanto o NGAL foi o que apresentou maior que com a desobstrução. Houve queda das concentrações dos marcadores após pieloplastia no período estudado. O papel exato dos biomarcadores urinários no cenário de obstrução em adultos deve ser mais amplamente investigado

Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report

Background. Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy. Case report. A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors. Conclusions. To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.

Cholangiocarcinoma: from molecular biology to treatment

Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.

The Banhado Alkaline Complex, Southeastern Brazil: source and evolution of potassic SiO2-undersaturated high-Ca and low-Ca magmatic series

The Cretaceous Banhado alkaline complex in southeastern Brazil presents two potassic SiO2-undersaturated series. The high-Ca magmatic series consist of initially fractionated olivine (Fo(92-91)) + diopside (Wo(48-43)En(49-35)Ae(0-7)), as evidenced by the presence of xenocrysts and xenoliths. In that sequence, diopside (Wo(47-38)En(46-37)Ae(0-8)) + phlogopite + apatite + perovskite (Prv(> 92)) crystallized to form the phlogopite melteigite and led to the Ca enrichment of the magma. Diopside (Wo(47-41)En(32-24) Ae(3-14)) continued to crystallize as an early mafic mineral, followed by nepheline (Ne(74.8-70.1)Ks(26.3-21.2)Qz(7.6-0.9)) and leucite (Lc(65-56)) and subsequently by melanite and potassic feldspar (Or(85-99)Ab(1-7)) to form melanite ijolites, wollastonite-melanite urtites and melanite-nepheline syenites. Melanite-pseudoleucite-nepheline syenites are interpreted to be a leucite accumulation. Melanite nephelinite dykes are believed to represent some of the magmatic differentiation steps. The low-Ca magmatic series is representative of a typical fractionation of aegirine-augite (Wo(36-29)En(25-4)Ae(39-18)) + alkali feldspar (Or(57-96)Ab(3-43)) + nepheline (Ne(76.5-69.0)Ks(19.9-14.4)Qz(15.1-7.7)) + titanite from phonolite magma. The evolution of this series from potassic nepheline syenites to sodic sodalite syenites and sodalitolites is attributed to an extensive fractionation of potassic feldspar, which led to an increase of the NaCl activity in the melt during the final stages forming sodalite-rich rocks. Phonolite dykes followed a similar evolutionary process and also registered some crustal assimilation. The mesocratic nepheline syenites showed interactions with phlogopite melteigites, such as compatible trace element enrichments and the presence of diopside xenocrysts, which were interpreted to be due to a mixing/mingling process of phonolite and nephelinite magmas. The geochemical data show higher TiO2 and P2O5 contents and lower SiO2 contents for the high-Ca series and different LILE evolution trends and REE chondrite-normalized patterns as compared to the low-Ca series. The Sr-87/Sr-86, Nd-143/Nd-144, Pb-206/Pb-204 and Pb-208/Pb-204 initial ratios for the high-Ca series (0.70407-0.70526, 0.51242-0.51251, 17.782-19.266 and 38.051-39.521, respectively) were slightly different from those of the low-Ca series (0.70542-0.70583, 0.51232-0.51240, 17.758-17.772 and 38.021-38.061, respectively). For both series, a CO2-rich potassic metasomatized lithospheric mantle enriched the source with rutile-bearing phlogopite clinopyroxenite veins. Kamafugite-like parental magma is attributed to the high-Ca series with major contributions from the melting of the veins. Potassic nephelinite-like parental magma is assigned to the low-Ca series, where the metasomatized wall-rock played a more significant role in the melting process.

Lille, France, ca. 1709 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan de la ville et citadelle de Lille, P. v. Call fecit. It was published by chez Anna Beek ca. 1709. Scale [ca. 1:9,281]. Covers Citadelle de Lille and a portion of Lille, France. Map in French.The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 31N projected coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas and selected buildings, fortifications, defenses, and lines of fire, ground cover, and more. Relief shown by hachures. Includes also index.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.