Fatal pulmonary thromboembolism in gastrectomy intraoperative procedures by gastric adenocarcinoma: case report

The case of a patient with gastric adenocarcinoma with indication for gastrectomy is reported. The surgery took place without complications. A palliative, subtotal gastrectomy was performed after para-aortic lymph nodes compromised by neoplasm were found, which was confirmed by pathological exam of frozen sections carried out during the intervention. At the end of the gastroenteroanastomosis procedure, the patient began to show intense bradycardia: 38 beats per minute (bpm), arterial hypotension, changes in the electrocardiogram's waveform (upper unlevelling of segment ST), and cardiac arrest. Resuscitation maneuvers were performed with temporary success. Subsequently, the patient had another circulatory breakdown and again was recovered. Finally, the third cardiac arrest proved to be irreversible, and the intra-operative death occurred. Necropsy showed massive pulmonary embolism. The medical literature has recommended heparinization of patients, in an attempt to avoid pulmonary thromboembolism following major surgical interventions. However, in the present case, heparinization would have been insufficient to prevent death. This case indicates that it is necessary to develop preoperative propedeutics for diagnosing the presence of venous thrombi with potential to migrate, causing pulmonary thromboembolism (PTE). If such thrombi could be detected, preventative measures, such as filter installation in the Cava vein could be undertaken.

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).

Meningeal carcinomatosis as the initial manifestation of a gallbladder adenocarcinoma associated with a Krukenberg tumor

A case of malignant neoplasm is described in which the initial manifestations were mental dysfunction and meningeal irritation, mimicking chronic or subacute meningitis. Physical examination showed cranial nerve involvement and a pelvic tumor. There was progressive deterioration, and death occurred in 2 weeks. The autopsy revealed a gallbladder adenocarcinoma, meningeal carcinomatosis, and ovarian metastasis presenting as a Krukenberg tumor. The authors emphasize the importance of including meningeal carcinomatosis as a possibility in the differential diagnosis of non-characteristic clinical pictures, as well as the importance of the cerebrospinal fluid cytologic examination, repeated as needed, in order to confirm this diagnosis.

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

RESUMO: Actualmente, a ��nica possibilidade de cura para doentes com adenocarcinoma do p��ncreas (PDAC) �� a ressec����o cir��rgica, no in��cio deste estudo, perguntamo-nos se os predictores cl��nico-patol��gicos cl��ssicos de prognostico poderiam ser validados em uma grande cohort de doentes com cancro do p��ncreas ressec��vel e se outros predictores cl��nicos poderiam ter um papel na decis��o de que doentes beneficiariam de ressec����o cir��rgica. No cap��tulo 2, observamos que at�� 30% dos doentes morrem no primeiro ano ap��s a ressec����o cir��rgica, pelo que o nosso objectivo foi determinar factores pr��-operat��rios que se correlacionam com mortalidade precoce ap��s resseca����o cir��rgica 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), complica����es p��s-operat��rias (p = 0,042), e mortalidade em 1 ano p��s- ressec����o cir��rgica (p <0,001). Um CACI superior a 6 triplicou a mortalidade no primeiro ano p��s-cirurgia e estes doentes t��m menos de 50% de probabilidade de estarem vivos um ano ap��s a cirurgia. No cap��tulo 3, o nosso objectivo foi identificar uma prote��na de superf��cie que se correlacionasse estatisticamente com o prognostico de doentes com adenocarcinoma do p��ncreas e permitisse a distin����o de subgrupos de doentes de acordo com as suas diferen��as moleculares, perguntamo-nos ainda se essa prote��na poderia ser um marcador de c��lulas-estaminais. No nosso trabalho anterior observamos que as c��lulas tumorais na circula����o sangu��nea apresentavam genes com caracter��sticas bifenot��pica epitelial e mesenquimal, enriquecimento para genes de c��lulas estaminais (ALDH1A1 / ALDH1A2 e KLF4), e uma super-express��o de genes da matriz extracelular (colag��nios, SPARC, e DCN) normalmente identificados no estroma de PDAC. Ap��s a avalia����o dos tumores prim��rios com RNA-ISH, muitos dos genes identificados, foram encontrados co-localizando em uma sub-popula����o de c��lulas na regi��o basal dos ductos pancre��ticos malignos. Al��m disso, observamos que estas c��lulas expressam o marcador SV2A neuroend��crino, e o marcador de c��lulas estaminais ALDH1A1/2. Em compara����o com tumores negativos para SV2, os doentes com tumores SV2 positivos apresentaram n��veis mais baixos de CA 19-9 (69% vs. 52%, p = 0,012), tumores maiores (> 4 cm, 23% vs. 10%, p = 0,0430), menor invas��o de g��nglios linf��ticos (69% vs. 86%, p = 0,005) e tumores mais diferenciados (69% vs. 57%, p = 0,047). A presen��a de SV2A foi associada com uma sobrevida livre de doen��a mais longa (HR: 0,49 p = 0,009) bem como melhor sobrevida global (HR: 0,54 p = 0,018). Em conjunto, esta informa����o aponta para dois subtipos diferentes de adenocarcinoma do p��ncreas, e estes subtipos co-relacionam estatisticamente com o prognostico de doentes, sendo este subgrupo definido pela presen��a do clone celular SV2A / ALDH1A1/2 positivo com caracter��sticas neuroend��crinas. No Cap��tulo 4, a express��o de SV2A no cancro do p��ncreas foi validado em linhas celulares prim��rias. Demonstramos a heterogeneidade do adenocarcinoma do p��ncreas de acordo com caracter��sticas clonais neuroend��crinas. 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 muta����o KRAS, prolifera����o e a resposta �� quimioterapia. No cap��tulo 5, perguntamo-nos se o clone celular SV2 positivo poderia explicar a resist��ncia a quimioterapia observada em doentes. Observamos um aumento absoluto de clones celulares expressando SV2A, em m��ltiplas linhas de evid��ncia - doentes, linhas de c��lulas prim��rias e xenotransplantes. Embora, tenhamos sido capazes de demonstrar que o adenocarcinoma do p��ncreas �� uma doen��a heterog��nea, consideramos que a caracteriza����o gen��tica destes clones celulares expressando SV2A �� de elevada import��ncia. Pretendemos colmatar esta limita����o com as seguintes estrat��gias: Ap��s o tratamento com quimioterapia neoadjuvante na nossa coorte, realizamos microdisseca����o a laser das amostras primarias em parafina, de forma a analisar muta����es gen��ticas observadas no adenocarcinoma pancre��tico; em segundo lugar, pretendemos determinar consequ��ncias de knockdown da express��o de SV2A em nossas linhas celulares seguindo-se o tratamento com gemicitabina para determina����o do papel funcional de SV2A; finalmente, uma vez que os nossos esfor��os anteriores com um promotor - rep��rter e SmartFlare ��� falharam, o pr��ximo passo ser�� realizar RNA-ISH PrimeFlow��� seguido de FACS e RNA-seq para caracteriza����o deste clone celular. Em conjunto, conseguimos provar com v��rias linhas de evid��ncia, que o adenocarcinoma pancre��tico �� uma doen��a heterog��nea, definido por um clone de c��lulas que expressam SV2A, com caracter��sticas neuroend��crinas. A presen��a deste clone no tecido de doentes correlaciona-se estatisticamente com o prognostico da doen��a, incluindo sobrevida livre de doen��a e sobrevida global. Juntamente com padr��es de prolifera����o e co-express��o de ALDH1A1/2, este clone parece apresentar um comportamento de c��lulas estaminais e est�� associado a resist��ncia a quimioterapia, uma vez que a sua express��o aumenta ap��s agress��o qu��mica, quer em doentes, quer em linhas de c��lulas prim��rias.----------------------------- 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.

Clear cell adenocarcinoma of the cervix in a young woman: a diagnostic challenge

Clear cell adenocarcinoma of the cervix is a rare tumor, classically related with in utero diethylstilbestrol (DES) exposure. The authors report a rare case of clear cell adenocarcinoma of the cervix in a 21-yearold woman who had no history of in utero DES exposure, presenting with intermittent vaginal bleeding. It stresses the relevance to always clarify the etiology of abnormal genital bleeding and consider the possibility of cervicovaginal tumors.

Marcadores tumorales (p53 y Ki67) en la secuencia metaplasia, displasia, adenocarcinoma en el es��fago de Barrett

La Enfermedad de Reflujo Gastroesof��gico (ERGE) constituye en gastroenterolog��a, junto con el s��ndrome de intestino irritable y la dispepsia, la patolog��a de m��s alta prevalencia. El reflujo gastroesof��gico (RGE) cr��nico y severo puede conducir a lesiones de la mucosa del es��fago distal, objetivables endosc��picamente, como Erosiones, Estenosis, Ulceras y Metaplasia Columnar. La Metaplasia Columnar (reemplazo del epitelio esof��gico por epitelio columnar) puede ser del tipo Cardial (transicional), G��strico F��ndico o Intestinal. La Metaplasia Intestinal (MI) se denomina Es��fago de Barrett, y es una condici��n precancerosa con alta prevalencia (del 5 al 20%). En nuestra casu��stica de los ��ltimos a��os gira siempre alrededor del 20%. La historia natural de la Enfermedad por Reflujo Gastroesof��gico es la siguiente: RGE ��� metaplasia cardial del epitelio esof��gico ��� carditis por reflujo - metaplasia intestinal ��� displasia ��� adenocarcinoma. ��C��mo se podr��a modificar esta historia natural?. A trav��s de la prevenci��n, la detecci��n precoz y el desarrollo de terap��uticas efectivas. La lesi��n histol��gica que aparece precediendo, y/o acompa��ando al adenocarcinoma (ACa) , es la displasia (D), definida como una alteraci��n citoarquitectural de los tejidos y de las c��lulas, muchas veces imprecisa y subjetiva, y que puede ser de bajo (DBG) y de alto grado (DAG). Como acercamiento al diagn��stico temprano del ACa, adem��s de la b��squeda de displasia, es posible detectar alteraciones moleculares o gen��ticas en los tejidos, mediante t��cnicas inmunohistoqu��micas, utilizando ciertos tipos de Marcadores Tumorales (MT). El objetivo principal de este trabajo es la detecci��n precoz (diagn��stico temprano del c��ncer) en el es��fago de Barrett en nuestro medio, mediante la utilizaci��n de los mencionados MT.

Adenocarcinoma c��stico hemorr��gico da gl��ndula mam��ria de camondongo

The A. A. have observed a hemorrhagic cyst-adenocacinoma of the mammary gland of mouse. This malignant tumor shows atipical, it is composed almost entirely of large cuboidal epithelial cells, which possess eosinophilic cytoplasm and generally hyperchromatic nuclei. There is a acinouslike structure. One can find many hemorragic areas, which form cyst-like blood filled spaces.

Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to esophageal adenocarcinoma.

Barrett's esophagus (BE) is an acquired condition in which the normal lining of the esophagus is replaced by intestinal metaplastic epithelium. BE can evolve to esophageal adenocarcinoma (EAC) through low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The only generally accepted marker for increased risk of EAC is the presence of HGD, diagnosed on endoscopic biopsies. More specific markers for the prediction of EAC risk are needed. A tissue microarray was constructed comprising tissue samples from BE, LGD, HGD, and EAC. Marker expression was studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2, SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi-quantitatively. CD44 expression decreased in HGD and EAC relative to BE and LGD. DKK1 expression increased in HGD and EAC relative to BE and LDG. CDX2 expression increased in HGD but decreased in EAC. COX2 expression decreased in EAC, and SOX9 expression increased only in the upper crypt epithelial cells in HGD. E-cadherin expression decreased in EAC. Nuclear beta-catenin was not significantly different between BE, LGD, and HGD. Loss of CD44 and gain of DKK1 expression characterizes progression from BE and LGD to HGD and EAC, and their altered expression might indicate an increased risk for developing an EAC. This observation warrants inclusion of these immunohistochemically detectable markers in a study with a long patient follow-up.

An��lisis retrospectivo de supervivencia y toxicidad en pacientes con adenocarcinoma g��strico avanzado tratados con el esquema DCF: Experiencia de un centro

Analizamos retrospectivamente una serie de 52 pacientes con adenocarcinoma ga��strico avanzado y tratados con el esquema DCF (docetaxel, cisplatino, 5-�����fluorouracilo) entre los an��os 2005 y 2011. La mediana de supervivencia ha sido de 6���53 meses y el tiempo hasta la progresio��n de 4���33 meses. Como factores prono��sticos independientes hemos obtenido el Performance Status basal (PS) y el sexo. Los pacientes con un PS2���3 presentan un riesgo de muerte de 2���68 veces mayor respecto al PS0-1, con una mediana de supervivencia de 4���33 meses, frente a la de 9���73 meses de los pacientes con un PS0-1. El esquema DCF en carcinoma ga��strico avanzado debe reservarse para los pacientes con un buen estado general basal.

Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53.

We report a 26-year-old female patient who was diagnosed within 4��years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18��months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations.

Ad��nocarcinome meibomien du bord libre palp��bral. A propos d'une observation [Meibomian adenocarcinoma of the free palpebral edge. Report of a case].

A case of meibomian carcinoma of the left eyelid is reported in a 72-year-old female patient. The tumor had been present on the left eyelid for months. Clinically, the tumor appeared as a reddish mass implanted on the external part of the free margin of the left superior eyelid. An excisional biopsy disclosed meibomian carcinoma. A total resection of the left superior eyelid was followed by plastic surgery. Results after a one-month follow-up were very satisfactory. This case is emphasizes the importance of an early diagnosis which enabled us to perform a rather conservative treatment limited to the removal of the affected eyelid. The diagnosis of meibomian carcinoma is infrequent but it must be kept in mind in cases of tumor without the typical clinical characteristics of a basal cell or squamous cell carcinoma. Complete removal surgery may bring a curative effect and histopathology has a key role in the diagnosis of meibomian carcinoma.