Sobre alguns casos de carcinoma primitivo do pulmão, do bronchio e da trachéa

1-Out of 1531 autopsies at Rio de Janeiro, Brazil, recorded in the Section of Pathology of «Instituto OSWALDO CRUZ», we found three cases of primary carcinoma of the lung, which gives the incidence of 0,195 per cent. They were not associated with tuberculos's and anthracos's was not marked. 2-The gross and microscopical features indicate that they are in reality primary cancers of the larger bronchi arising probably, from the bronchial lining epithelium. There is a striking similarity both macro and microscopical in Cases I and II, where the structure is that of cylindrical cell alveolar carcinoma. Mucus formation was never a prominent feature in these tumors. As in HENRICI's case they apparently invade the lung along the alveolar wall in more or less considerable extension retaining the alveolar septa as stroma. In case III the structure is that of squamous cell carcinoma, and the tumor mass, usually ulcerating, lies in the immediate vicinity of the bronchi, the extension to the lung tissue being not widespread. 3-Cases IV and V are tumors of the lower and median portion of the trachéa, squamous cell carcinoma in structure, which form marked contrast with the tumors originating in the larger bronchi: the tumor process never invades the lung parenchyma by continuous extension. In Case V extension to the mediastinal lymph-nodes is observed, and a tumor of the size of an orange is found in the anterior mediastinum: that tumor mass and the upper lobe of the right lung were only adherent by fibrous tissue of inflammatory origin and the tumor did not extend into the lung tissue.

Carcinoma epidermoide primario do estomago

Os AA. chamam a attenção para a raridade deste typo histologico de tumor do estomago e descrevem um caso verificado pela autopsia, em individuo branco, brasileiro, de 67 annos de edade. O tumor localiza-se na pequena curvatura do estomago, sob o aspecto de uma formação crateriforme de 3,5 cms. de diametro e com adherencias ao pancreas. O esophago e o cardia não são de modo algum comprometidos pelo processo. Foram encontradas metastases no coração, no figado, na capsula do pancrea, no pulmão e glandulas suprarenaes. O exame histologico mostra tratar-se de um carcinoma epidermoide, não só no tumor primitivo, como tambem nos fócos metastaticos. As AA. são inclinados a acreditar que o tumor tenha se originado por intermedio de um processo d metaplasia epidermoide da mucosa gastrica.

Carcinoma primário do pulmão

Em um período de 23 anos, de 1919 a 1941, observaram-se 25 casos de carcinoma primário do pulmão entre o total de 6.458 necrópsias, registadas na Secção de Anatomia Patológica do Instituto Osvaldo Cruz e realizadas nos vários hospitais do Rio de Janeiro. Os indivíduos eram de procedência variada, não só de diferentes regiões do Brasil, como também de alguns países estrangeiros. A incidência do carcinoma primário do pulmão, considerado como causa mortis, entre o total das necrópsias e de 0,38 % e, entre os casos de cancer, 4,5 %. Em referência ao sexo, 21 casos eram de indivíduos masculinos (84 %) e 4 femininos (16 %), fornecendo a relação de 5:1. Dos 25 casos, 13 (52 %) eram de nacionalidade estrangeira e 12 (48 %) brasileira; 18, em indivíduos de cor branca, 6 pretos e 1 pardo. Em relação à idade, a maior incidência ocorreu entre 41 e 70 anos, com o máximo entre 51 a 60, existindo casos extremos de 21 e 93 anos. A forma anatômica mais freqüente, no mesmo material, e a infiltrante hilar, 16 casos (64 %), seguindo-se a nodular, com 7 casos (28 %) e a difusa, 2 casos (8) . O carcinoma de células indiferenciadas é o tipo histológico mais comum, existindo em 13 casos (52 %), seguindo-se o tipo de células cilíndricas, em 8 casos (32 %) e o de células pavimentosas em 4 casos (16 %). A incidência das metastases foi observada em 22 casos (88 %), sendo, para o carcinoma de células indiferenciadas, de 76,9 %, e, tanto para o carcinoma de células cilíndricas como para o de células pavimentosas, de l00%. Em três casos (12 %), não foram observadas metástases. Entre os orgãos sede frequente das metástases, foi observada a seguinte relação: gênglios linfáticos, 72 %; fígado, 56 %; pleura, 12 %; peritônio, pericárdio, rins e suprarrenal, 8 %; cérebro e osso, 4 %. Nos últimos 10 anos (1932 a 1941), ocorreram 16 casos (64 % do total dos 25 encontrados), demostrando senão o aumento do cancer pulmonar, certamente o maior número de diagnostico positivos.

Carcinoma metastatico do baço

Among the material of the archives of the Pathological Section of the Oswaldo Cruz Institue (Rio de Janeiro, Brasil) we found 9 cases of cancer metastasis in the spleen. Four of them were macroscopically apparent, but five had only been diagnosed microscopically. Of these cases of tumors, 3 are adenocarcinoma originated from the pancreas (cases 1, 3, 5,); 3 are primary carcinoma of stomach (cases 7,8 and 9); 1 adenocarcinoma of gall-bladder (case 2); 1 originated form the mammary gland (case 4) and finally 1 form the colon. (case 6.). The incidence of the metastasis observed in the spleen among the total of 6.400 studied autopsies is of 0,14%; The same incidence among those of epithelial blastomata is of 1,8%.

Carcinoma primário do pâncreas

O estudo anatomopatológico baseado em uma coleção de 6823 necrópsias, constantes do arquivo da Seção de Anatomia Patológica do Instituto Oswaldo Cruz, Rio de Janeiro, Brasil, realizadas durante os anos de 1919 a 1944, revelou a existência de 28 casos de carcinoma primário do pâncreas. A incidência deste tipo de tumor entre o total das necropsias examinadas atinge a 0,40% e, entre os casos de câncer observados na referida série de necrópsias, a 4,08%. O tumor localizou-se na cabeça do pâncreas em 20 casos (71,4%); na cauda, em um caso (3,5%); difuso, em cinco casos (17,8%) e sem localização precisada, em dois casos (7,1%). O tipo histológico predominante foi o adenocarcinoma, reconhecido em 2 casos (78,57%); e em seguida o carcinoma acinoso, em seis casos (21,43%). Geralmente se observa o tipo cirrótico e, em alguns casos, era pronunciada a formação de mucina. A incidência das metástases, em relação aos casos de adenocarcinoma, foi de 95,45% (21 vêzes em 22 casos) e, em relação ao carcinoma acinoso, de 100% (6 vêzes em 6 casos). Entre os órgãos atingidos pelas metástases citam-se em ordem decrescente: o fígado e os gânglios linfáticos (70,3%) o peritônio (25,9%), o pulmão (22,2%), a suprarrenal (18,5%), a pleura bago e rim (7,4%), os intestinos, tiróide, pericárdio, epiploon, estomago, ovário e seio venoso longitudinal superior (3,7%).Em um só caso, não houve produção de metástase (3,57%). Em relação às metástases no peritônio, é interessante acentuar a sua maior freqüência nos casos de adenocarcinoma (7 vêzes em 22 casos). A distribuição do tumor, segundo o sexo, foi de 19 casos em indivíduos do sexo masculino (67,8%) e nove casos, para os do sexo feminino (32,1%), fornecendo a relação de cêrca de 2:1. Segundo a nacionalidade, observaram-se 21 casos (75%) em brasileiros e sete casos (25%) em estrangeiros. Segundo a côr, em 15 casos (53,5%) eram indivíduos de côr branca, em oito casos, (28,5%) de côr preta e, em cinco casos (17,8%), de côr parda. O maior número de casos, em referência à idade, ocorreu em indivíduos de 41 a 50 anos, quando a incidência foi de 11 casos ou 39,3% do total dos casos observados. Em referência a ocorrência anual, verifica-se o maior número (22 casos ou 78,9%) nos últimos dez anos, isto e, de 1935 a 1944.

Inhibitory effect of cyclophosphamide on the biosynthesis of a perchloro-soluble protein fraction of ehrlich ascites carcinoma cells

The perchloro-soluble mucroptotein fraction was determined in the cells of Ehrlich ascites carcinoma on the 10th and 12th days post-inoculation of the tumor. After 3 days of a single subcutaneous dose of cyclophosphamide (200 mg/kg) the mucoprotein levels were found considerable lower. This difference was highly significant statistically.

Acute Eosinophilic and Neutrophilic Pneumonia following Transarterial Chemoembolization with Drug-Eluting Beads Loaded with Doxorubicin for Hepatocellular Carcinoma: A Case Report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization. © 2014 S. Karger AG, Basel.

Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy.

Autophagy or "self eating" is frequently activated in tumor cells treated with chemotherapy or irradiation. Whether autophagy represents a survival mechanism or rather contributes to cell death remains controversial. To address this issue, the role of autophagy in radiosensitive and radioresistant human cancer cell lines in response to gamma-irradiation was examined. We found irradiation-induced accumulation of autophagosomes accompanied by strong mRNA induction of the autophagy-related genes beclin 1, atg3, atg4b, atg4c, atg5, and atg12 in each cell line. Transduction of specific target-siRNAs led to down-regulation of these genes for up to 8 days as shown by reverse transcription-PCR and Western blot analysis. Blockade of each autophagy-related gene was associated with strongly diminished accumulation of autophagosomes after irradiation. As shown by clonogenic survival, the majority of inhibited autophagy-related genes, each alone or combined, resulted in sensitization of resistant carcinoma cells to radiation, whereas untreated resistant cells but not sensitive cells survived better when autophagy was inhibited. Similarly, radiosensitization or the opposite was observed in different sensitive carcinoma cells and upon inhibition of different autophagy genes. Mutant p53 had no effect on accumulation of autophagosomes but slightly increased clonogenic survival, as expected, because mutated p53 protects cells by conferring resistance to apoptosis. In our system, short-time inhibition of autophagy along with radiotherapy lead to enhanced cytotoxicity of radiotherapy in resistant cancer cells.

ATP-competitive inhibitors of mTOR: new perspectives in the treatment of renal cell carcinoma.

Targeting mTOR (mammalian target of rapamycin) is an effective approach in the treatment of advanced RCC (renal cell carcinoma). Rapamycin-like drugs (rapalogues) have shown clinical activities and have been approved for the treatment of RCC. Recently, with the development of ATP-competitive inhibitors of mTOR, therapies targeting mTOR have entered a new era. Here, we discuss the biological relevance of blocking mTOR in RCC and review the mechanisms of action of rapalogues in RCC. We also advance some perspectives on the use of ATP-competitive inhibitors of mTOR in RCC.

Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial : B-241

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.

Correlation of tumor-associated antigens MAGE, NY-ESO-1 and P53 expression with clinical and pathological relationships of patients with oral squamous cell carcinoma

Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma.

Cancer-testis (CT) antigens comprise families of tumor-associated antigens that are immunogenic in patients with various cancers. Their restricted expression makes them attractive targets for immunotherapy. The aim of this study was to determine the expression of several CT genes and evaluate their prognostic value in head and neck squamous cell carcinoma (HNSCC). The pattern and level of expression of 12 CT genes (MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, MAGE-C2, NY-ESO-1, LAGE-1, SSX-2, SSX-4, BAGE, GAGE-1/2, GAGE-3/4) and the tumor-associated antigen encoding genes PRAME, HERV-K-MEL, and NA-17A were evaluated by RT-PCR in a panel of 57 primary HNSCC. Over 80% of the tumors expressed at least 1 CT gene. Coexpression of three or more genes was detected in 59% of the patients. MAGE-A4 (60%), MAGE-A3 (51%), PRAME (49%) and HERV-K-MEL (42%) were the most frequently expressed genes. Overall, the pattern of expression of CT genes indicated a coordinate regulation; however there was no correlation between expression of MAGE-A3/A4 and BORIS, a gene whose product has been implicated in CT gene activation. The presence of MAGE-A and NY-ESO-1 proteins was verified by immunohistochemistry. Analysis of the correlation between mRNA expression of CT genes with clinico-pathological characteristics and clinical outcome revealed that patients with tumors positive for MAGE-A4 or multiple CT gene expression had a poorer overall survival. Furthermore, MAGE-A4 mRNA positivity was prognostic of poor outcome independent of clinical parameters. These findings indicate that expression of CT genes is associated with a more malignant phenotype and suggest their usefulness as prognostic markers in HNSCC.