Cancers of unknown primary diagnosed during hospitalization: a population-based study

Background: Cancers of Unknown Primary (CUP) are the 3-4th most common causes of cancer death and recent clinical guidelines recommend that patients should be directed to a team dedicated to their care. Our aim was to inform the care of patients diagnosed with CUP during hospital admission. Methods: Descriptive study using hospital admissions (Scottish Morbidity Record 01) linked to cancer registrations (ICD-10 C77-80) and death records from 1998 to 2011 in West of Scotland, UK (population 2.4 m). Cox proportional hazards models were used to assess effects of baseline variables on survival. Results: Seven thousand five hundred ninety nine patients were diagnosed with CUP over the study period, 54.4% female, 67.4% aged ≥ 70 years, 36.7% from the most deprived socio-economic quintile. 71% of all diagnoses were made during a hospital admission, among which 88.6% were emergency presentations and the majority (56.3%) were admitted to general medicine. Median length of stay was 15 days and median survival after admission 33 days. Non-specific morphology, emergency admission, age over 60 years, male sex and admission to geriatric medicine were all associated with poorer survival in adjusted analysis. Conclusions: Patients with a diagnosis of CUP are usually diagnosed during unplanned hospital admissions and have very poor survival. To ensure that patients with CUP are quickly identified and directed to optimal care, increased surveillance and rapid referral pathways will be required

Cutaneous metastasis of occult breast cancer: a case report

Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case

Neuroendocrine Tumor of Unknown Primary Accompanied with Stomach Adenocarcinoma

A 67 year old male at a regular checkup underwent esophagogastroduodenoscopy. On performing esophagogastroduodenoscopy, a lesion about 1.2 cm depressed was noted at the gastric angle. The pathology of the biopsy specimen revealed a well-differentiated adenocarcinoma. On performing an abdominal computed tomography (CT) scan & positron emission tomography-computed tomography (PET-CT) scan, no definite evidence of gastric wall thickening or mass lesion was found. However, lymph node enlargement was found in the left gastric and prepancreatic spaces. This patient underwent laparoscopic assisted distal gastrectomy and D2 lymph node dissection. On final examination, it was found out that the tumor had invaded the mucosal layer. The lymph node was a metastasized large cell neuroendocrine carcinoma with an unknown primary site. The patient refused chemotherapy. He opted to undergo a close follow-up. At the postoperative month 27, he had a focal hypermetabolic lesion in the left lobe of the liver that suggested metastasis on PET-CT scan. He refused to undergo an operation. He underwent a radiofrequency ablation

Lymph node reactivity and microvessel density in neck metastases of unknown primary squamous cell carcinoma

BACKGROUND: neoangiogenesis and the immune response are important mechanisms in metastasis development. AIM: to evaluate lymph node reactivity and microvessel density in neck metastasis of occult primary squamous cell carcinoma considering their histological and clinical variables. STUDY DESIGN: retrospesctive case-series. METHOD: 19 patients with neck metastasis of occult primary squamous cell carcinoma who underwent neck dissection between 1983 and 2000 were selected. The lymph nodes were reevaluated on the type of reactivity in both the cortical and paracortical areas, and the metastasis were assessed as to grade, desmoplasia, necrosis and microvessel density (CD34). The relationship between histological and clinical variables was evaluated. RESULTS: the median microvessel density was 91 vessels/mm2, varying from 28 to 145. Paracortical hyperplasia was more common in patients below 55 years of age (90% x 44%, p= 0.05), but there was no relationship between reactivity patterns and microvessel density with prognosis. The disease-free survival was 52% in 3 years, being similar in both groups, with higher or lower microvessel densities. CONCLUSION: microvessel density in neck metastasis of occult primary squamous cell carcinoma had a great individual variability. It wasn t possible to establish the relationship between microvessel density and the clinical or histological variables studied.INTRODUÇÃO: A neoangiogênese e a resposta imunológica são mecanismos importantes no desenvolvimento das metástases. OBJETIVO: Avaliar a reatividade linfonodal e a densidade microvascular nas metástases cervicais de carcinoma epidermóide com tumor primário oculto, considerando a sua relação com outras variáveis histológicas e clínicas. TIPO DE ESTUDO: Série de casos, retrospectiva. CASUÍSTICA E MÉTODO: 19 pacientes submetidos a esvaziamento cervical entre 1983 e 2000. Os linfonodos foram reavaliados quanto ao tipo de reatividade, considerando a área cortical e paracortical. Nas metástases foi avaliado o grau de diferenciação, desmoplasia, necrose, e densidade microvascular (CD34). Foi estabelecida a relação entre as diferentes variáveis histológicas e clínicas, incluindo o estadiamento e a evolução dos pacientes. RESULTADOS: A densidade microvascular apresentou mediana de 91 vasos/mm2, variando de 28 a 145. A reatividade paracortical foi mais freqüente nos pacientes com menos de 55 anos (90% x 44%, p= 0,05). A sobrevida livre de doença foi de 52% em 3 anos, sendo similar entre os pacientes com maior ou menor densidade microvascular tumoral. CONCLUSÕES: A densidade microvascular nas metástases de tumor primário oculto apresenta grande variação individual. Não foi possível estabelecer relação entre a densidade microvascular e as variáveis clínicas e histológicas estudadas.Hospital HeliópolisCentro Universitário PositivoEscola Paulista de MedicinaUNIFESP, EPMSciEL

Unknown primary large-cell neuroendocrine tumor

Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal tract, although they are potentially ubiquitous throughout the body. Primary unknown NET has a worse prognosis and shorter survival comparing with other NETs, with limited available data in the literature concerning this subgroup. The authors report the case of large-cell NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two infracentimetric lung lesions that could not be accessed for biopsy and were negative at both somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed with three mediastinal masses, so the patient was started on chemotherapy with carboplatin and etoposide with initial total response. Early progression showed no response to further chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated with local radiotherapy. This patient has an atypical long survival (54 months) compared to the literature data. In fact, there are few long-term survivors of large-cell NET and they are all related to complete surgical resection

Significance of serum tumor markers monitoring in carcinomas of unknown primary site

Background/Aim. Unknown primary tumors represent a heterogeneous group of malignancies that are indicative of ominous prognosis. Cancer of unknown primary site (CUP) is defined as the lack of any detectable primary site after full evaluation, and accounts for approximately 3-5% of all newly diagnosed patients with malignancies. The aim of this report was to present the prognostic and predictive value of 8 serum tumor markers in this group of patients. Methods. The study involved 63 patients. On histological examination, all the patients were presented with metastatic tumors whose primary site (origin) could not be detected with noninvasive diagnostic techniques. Following the routine light microscopy, all histological findings were classified into one of the following three groups: plano-cellular carcinoma - 8 patients; adenocarcinoma - 33 patients; unclassifiable (undifferentiated) carcinoma - 22 patients. In all the cases we evaluated 8 serum tumor markers: alpha-fetoproteins (AFP), chronic gonadotrophin beta submit, human (beta-HCG), neuron specific enolase (NSE), marker of malignant ovarian tumors (CA 125), prostate-specific antigene (PSA), marker of malignant brest tumor (CA 15-3), marker of malignant pancreas tumor and gastrointestinal tumor (Ca 19-9), carcinoembryonic antigen (CEA) at the time of diagnosis. The patients on chemotherapy had the markers determined after the third and sixth chemocycle, i.e. at the time of illness progression observation, if present. The patients responding to chemotherapy with complete response (CR), partial response (PR) or stable disease (SD) had the markers determined after three-month periods until the time of relapse or progression. Chemotherapy was applied in 32 patients (20 females and 12 males), aged 29-70 years, who met the inclusion criteria. The following chemotherapy regimen was used: doxorubicin 50mg/m2 (day 1), cisplatin 60mg/m2 (day 1), and etoposide 120 mg/m2 (days 1-3). The period between two chemotherapy cycles was three weeks, and maximum five weeks in the case of prolonged hematological toxicity. Results. Most commonly elevated were NSE values (82.54%), while AFP values were least commonly elevated (11.11%). Average survival time was 17.89 months (95%CI 12.96; 22.83). The probability of 24 months' survival was 0.228. The group of 32 patients treated with chemotherapy had 12 (37.5%) fatal outcomes in the observed period (72 months). Average survival time was 26.6 months (95% CI 19.5; 33.7). Average tumor marker values before and after the chemotherapy were significantly lower for NSE and CA 125. Survival was significantly better in cases of NSE and CA 125 decrease of more than 20%. Conclusion. Increased values of serum tumor markers are very often in CUP. The tumors show nonspecific overexpression of tumor markers. The NSE and CA 125 levels show good correlation with response to the given chemotherapy. However, a routine evaluation of commonly used serum tumor markers has not been proven of any prognostic and predictive assistance

Perfil epidemiologico e histopatologico do melanoma cutaneo em um centro do nordeste brasileiro de 2000 a 2010

BACKGROUND:While representing only 3-4% of malignant skin tumors, cutaneous melanoma is the most aggressive and lethal. Statistical knowledge about the biological behavior of this tumor is essential for guiding daily outpatient practice and aiding public health policies.OBJECTIVES:To analyze the profile of patients with cutaneous melanoma attending a pathology department in Teresina (state of Piauí) between 2000 and 2010.METHODS:Retrospective study of melanoma patients diagnosed between 2000 and 2010 in the São Marcos Hospital in the city of Teresina. The pathology laboratory reports were studied and all the statistical analyses performed using SPSS 19.0.RESULTS:A total of 25 in situ, 199 invasive and 89 metastatic melanomas of unknown primary site were observed. Histological types found were nodular (52.8%), superficial spreading melanoma (18.6%), acral (10.6%) and lentigo maligna (9.5%). In 144 (73.4%) cases the Breslow thickness was >1 mm. Metastasis was found in 28.6% of invasive melanomas and nodular melanoma, Clark IV/ V, Breslow > 1 mm, mitotic index > 6 and ulcerated lesions were more likely to metastasize.CONCLUSION:Most melanomas presented Breslow> 1mm. The main factors associated with metastasis were nodular type, Clark IV / V, Breslow> 1mm, mitotic index > 6 and ulcerated lesions.FUNDAMENTOS:Apesar de representar apenas 3-4% dos tumores malignos de pele, o melanoma cutâneo é o mais agressivo e letal deles. O conhecimento estatístico do comportamento biológico deste tumor em nosso meio ambiente é fundamental para orientar a prática ambulatorial diária e para auxiliar políticas de saúde pública.OBJETIVOS:Analisar o perfil de pacientes com melanoma cutâneo diagnosticados em serviço de referência em patologia em Teresina-Piauí no período de 2000 a 2010.MÉTODOS:Estudo retrospectivo de pacientes com melanoma diagnosticados entre 2000 e 2010 no Hospital São Marcos, Teresina-Piauí-Brasil. Estudou-se laudos histopatológicos e realizou-se análises estatísticas com o programa SPSS 19,0.RESULTADOS:Um total de 25 melanomas in situ, 199 invasivos e 89 metastáticos de sítio primário desconhecido foram observados. Tipos histológicos encontrados foram nodular (52,8%), melanoma extensivo superficial (18,6%), acral (10,6%) e lentigo maligno (9,5%). Em 144 (73,4%) casos o índice de Breslow foi >1 mm. Verificou-se metástases em 28,6% dos melanomas invasivos e melanoma nodular, Clark IV/V, Breslow >1 mm, índice mitótico ≥6 e lesões ulceradas estavam mais propensos a metástases.CONCLUSÃO:Melanomas com Breslow >1mm foram os casos predominantes. Principais fatores associados a metástase foram tipo nodular, Clark IV/V, Breslow >1mm, índice mitótico ≥6 e lesões ulceradas.Piaui Federal UniversityFederal University of São PauloUSP Ribeirao Preto Medical FacultySao Marcos HospitalFederal University of PiauiUNIFESPSciEL

Robottiavusteinen kirurgia nielusyövän hoidossa

HALO-katsaus•Ha­vain­noivien vertai­lu­tut­ki­musten ja klii­nisen koke­muksen perus­teella tran­so­raa­linen robot­ti­ki­rurgia vai­kuttaa lupaa­valta mene­tel­mältä vali­koi­duissa poti­las­ryh­missä, mut­ta tutki­mus­näyttö vaikut­ta­vuu­desta ja turval­li­suu­desta on toistai­seksi puutteel­lista ja heikko­laa­tuista

Association of pregnancy complications/risk factors with the development of future long-term health conditions in women : overarching protocol for umbrella reviews

Acknowledgments Patient representatives and MuM-PreDiCT team. Funding This work was funded by the Strategic Priority Fund 'Tackling multimorbidity at scale' programme (grant number-MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health and Care Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council.Peer reviewedPublisher PD

Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study

[EN] Objective To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Methods Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. Results In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 +/- 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 +/- 0.054) and melanoma BM (eight features, AUC = 0.936 +/- 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 +/- 0.180). Conclusion Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels.This work has been partially funded by the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds under Grant BFU2015-64380-C2-2-R. Rafael Ortiz-Ramon was supported by grant ACIF/2015/078 from the Conselleria d'Educacio, Investigacio, Cultura i Esport of the Valencian Community (Spain). Andres Larroza was supported by grant FPU12/01140 from the Spanish Ministerio de Educacion, Cultura y Deporte (MECD).Ortiz-Ramón, R.; Larroza-Santacruz, A.; Ruiz-España, S.; Arana Fernandez De Moya, E.; Moratal, D. (2018). Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study. European Radiology. 28(11):4514-4523. https://doi.org/10.1007/s00330-018-5463-6S451445232811Gavrilovic IT, Posner JB (2005) Brain metastases: epidemiology and pathophysiology. J Neurooncol 75:5–14Stelzer KJ (2013) Epidemiology and prognosis of brain metastases. Surg Neurol Int 4:S192–S202Soffietti R, Cornu P, Delattre JY et al (2006) EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. 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