Nonsmall cell lung cancer: evaluation of 737 consecutive patients in a single institution

OBJECTIVE: To analyze surgical and pathological parameters and outcome and prognostic factors of patients with nonsmall cell lung cancer (NSCLC) who were admitted to a single institution, as well as to correlate these findings to the current staging system. METHOD: Seven hundred and thirty seven patients were diagnosed with NSCLC and admitted to Hospital do Cancer A. C. Camargo from 1990 to 2000. All patients were included in a continuous prospective database, and their data was analyzed. Following staging, a multidisciplinary team decision on adequate management was established. Variables included in this analysis were age, gender, histology, Karnofsky index, weight loss, clinical stage, surgical stage, chemotherapy, radiotherapy, and survival rates. RESULTS: 75.5% of patients were males. The distribution of histologic type was squamous cell carcinoma 51.8%, adenocarcinoma 43.1%, and undifferentiated large cell carcinoma 5.1%. Most patients (73%) presented significant weight loss and a Karnofsky index of 80%. Clinical staging was IA 3.8%, IB 9.2%, IIA 1.4%, IIB 8.1%, IIIA 20.9%, IIIB 22.4%, IV 30.9%. Complete tumor resection was performed in 24.6% of all patients. Surgical stage distribution was IA 25.3%, IB 1.4%, IIB 17.1%, IIIA 16.1%, IIIB 20.3%, IV 11.5%. Chemotherapy and radiotherapy were considered therapeutic options in 43% and 72%, respectively. The overall 5-year survival rate of nonsmall cell lung cancer patients in our study was 28%. Median survival was 18.9 months. CONCLUSIONS: Patients with NSCLC who were admitted to our institution presented with histopathologic and clinical characteristics that were similar to previously published series in cancer hospitals. The best prognosis was associated with complete tumor resection with lymph node dissection, which is only achievable in earlier clinical stages.

P53 and Rb tumor suppressor gene alterations in gastric cancer

Inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. Our purpose was to study the involvement of p53, APC, DCC, and Rb genes in gastric carcinoma. METHOD: Loss of heterozygosity of the p53, APC, DCC and Rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35S-dATP, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone. RESULTS AND DISCUSSION: No loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the Rb gene in 23% (3/13) of the cases of intestinal-type gastric carcinoma. Eighteen (81.8%) cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. The presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%). Normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. The correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (P = .90). There was no correlation of gene alterations with the disease severity. CONCLUSIONS: The inactivation of Rb and p53 genes is involved in gastric carcinogenesis in our environment. Loss of the Rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with Helicobacter pylori infection. The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.

Umbilical mass as the sole presenting symptom of pancreatic cancer: a case report

Umbilical nodes are rare. The metastatic involvement of the region was first described in 1846. Sister Mary Joseph was the first observer to establish the correlation between carcinomas and umbilical nodes. The umbilical node may be the sole presenting sign of cancer and is usually associated with advanced disease and poor prognosis. A 64-year-old woman, previously healthy, presented vague abdominal discomfort and a hard umbilical nodule for 1 week, which was first diagnosed as an incarcerated umbilical hernia. She underwent a new clinical assessment and biopsy. After immunohistochemical analysis and computerized tomography, she was diagnosed with pancreatic cancer. The clinical staging showed advanced disease with distant metastasis. She received palliative chemotherapy. After 8 months, she was alive in poor clinical condition. Clinical suspicion should lead to a careful additional evaluation whenever an umbilical nodule presents with malignant signs.

Microsatellite instability in solitary and sporadic gastric cancer

Recently, the presence of microsatellite instability (MSI) has been reported in gastric cancer and associated with older age of presentation, distal tumor location, early disease staging, and better overall prognosis. Different characteristics in presentation and in tumor behavior may be explained by different genetic alterations during carcinogenesis of gastric cancer. Identification of specific genetic pathways in gastric cancer may have direct impact on prognosis and selection of treatment strategies. PATIENTS AND METHODS: All 24 patients were treated by radical surgery. Fragments of normal and tumor tissues were extracted from the specimen and stored at -80ºC before DNA purification and extraction. PCR amplification utilizing microsatellite markers was performed. Tumors presenting PCR products of abnormal sizes were considered positive for microsatellite instability (MSI+). RESULTS: Five patients (21%) had tumors that were MSI+ in at least 1 marker. In the group of patients with Lauren's intestinal-type gastric carcinoma, 3 had tumors that were MSI+ (23%), while in the group of diffuse-type gastric cancer, 2 patients had tumors that were MSI+ (19%). The mean age of presentation and the male:female ratio was similar in both groups. Tumors that were MSI+ were more frequently located in proximal portion of the stomach compared to microsatellite-stable (MSS) tumors (40% vs. 16%). Although there was a trend of patients with MSI+ tumors towards a proximal gastric tumor location, early staging, and negative lymph node metastasis, there was no statistical significance compared to those with MSS tumors (P >.1). Comparison of overall and disease-free survival between gastric tumors that were MSI+ and those that were MSS found no statistically significant differences (P >.1). CONCLUSIONS: Microsatellite instability is a frequent event in gastric carcinogenesis and shows a trend towards distinct clinical and pathological characteristics of gastric cancer.

Prognostic factors in locally advanced colon cancer treated by extended resection

The impact of clinical, pathologic, and surgical variables on the postoperative morbidity, mortality, and survival of patients undergoing extended resections of colon carcinoma were evaluated. METHODS: The medical records of 95 patients who underwent extended resections for colon carcinoma between 1953 and 1996 were reviewed. In all cases, in addition to colectomy, 1 or more organs and/or structures were resected en bloc due to a macroscopically based suspicion of tumor invasion. The clinical, pathologic, and surgical parameters were analyzed. Overall survival rates were analyzed according to the method of Kaplan and Meier. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Eighty-six patients were treated by curative surgeries and the remaining by palliative resections. Invasion of the organs and/or adjacent structures and regional lymph nodes was found microscopically in 48 and 31 patients, respectively. The median follow-up without postoperative mortality was 47.7 months. The 5-year overall survival rates was 52.6%. The 5-year overall survival rates for patients undergoing curative and palliative surgeries was 58.3% and 0%, respectively. The mean survival time in the palliative surgery group was 3.1 months. Multivariate analysis showed that Karnofsky performance status was strongly related to the risk of postoperative complications (P = .01), and postoperative deaths were associated with the type of surgery and Karnofsky performance status at the time of admission (P = .001). CONCLUSIONS: Some patients with locally advanced colon adenocarcinomas undergoing extended resections have a 5-year overall survival rates of 58.3%. Patients could benefit from palliative-intent procedures, but these measures should cautiously be indicated and avoided in patients with low Karnofsky performance status due to high rates of postoperative mortality and poor survival.

Cytotoxic evaluation of essential oil from Casearia sylvestris Sw on human cancer cells and erythrocytes

A Casearia sylvestris (Flacourtiaceae) é uma planta popularmente conhecida como "guaçatonga" e é usada por povos indígenas da América do sul (Brasil, Peru e Bolivia) no tratamento de muitas doenças, incluindo câncer. Estudos citotóxicos mostraram que esta planta apresenta um possível e interessante potencial antitumoral devido à presença de moléculas chamadas casearinas. Além disso, a composição do óleo essencial mostrou uma alta concentração de sesquiterpenos de alto potencial citotóxico. Neste trabalho, nós verificamos que o óleo essencial da C. sylvestris apresentou uma boa citotoxicidade seletiva contra as linhagens de células tumorais HeLa, A-549 and HT-29 (CD50 63,3, 60,7 e 90,6 µg.ml-1, respectivamente) quando comparada às células não-tumorais Vero (CD50 210,1 µg.ml-1) e macrófagos de camundongos (CD50 234,0 µg.ml-1). Além disso, o óleo causou hemólise em sete diferentes tipos de eritrócitos, indicando que a C. sylvestris precisa ser usada com cuidado. Também foram testados padrões de β-cariofileno e α-humuleno que mostraram citotoxicidade similar àquelas apresentadas pelo óleo, indicando que estes compostos podem ser os responsáveis pelos efeitos tóxicos que foram observados neste estudo.

Hypertension in Patients with Cancer

There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

Multiplicações celulares e tumores induzidos por virus: o cancer como infecção

Após terem sido apreciadas, à luz de fatos experimentais, as principais causas determinantes das multiplicações celulares normais e aquelas responsabilidades pelas multiplicações anormais, encontradas nos tumores blastomatosos, foram analisados os tumores animais que reconhecidamente são causados por virus tais como: o sarcoma e o epitelioma das galinhas; o papiloma e o mixoma dos coelhos; os carcinomas de ratos e rãs, e finalmente, o papiloma oral e o linfo-sarcoma venéreo dos cães. Em seguida, foram focalizadas as várias propriedades em comum existentes entre os vírus indutores dêsses tumores como: capacidade de determinar multiplicações anormais nos tecidos atacados; elevada especificidade para as espécies sensíveis; existência de diminuição do poder infeccioso à medida que aumenta a capacidade de estimular a formação de tumores e, as afinidades existentes entre êles e os gens, principalmente àquelas referentes à sensibilidade aos raios X. Finalmente, foi aventada a hipótese da possível existência de elementos patogênicos ainda não identificados, situados entre os virus citocinéticos conhecidos e os gens, com poder infeccioso mínimo, exigindo por isso, condições de susceptibilidade ainda não totalmente conhecidas e controladas, possuidores de elevado poder de induzir multiplicações anormais nos tecidos atacados e possìvelmente responsáveis pelos tumores neoplásicos humanos.

Methionine enkephalin: immunomodulator in normal volunteers, cancer and AIDS patients

Clinical studies of the immunological effects of methionine enkephalin in normal volunteers, cancer, and AIDS patients are summarized. The major immunology changes seen were increases in T cell subsets, natural killer activity, as well as mitogen blastogenesis. Clinically, the cancer and ARC patients did not develop infections.

Human papillomavirus infection and cervical cancer in Brazil: a retrospective study

Two hundred and thirty paraffin-embedded biopsies obtained from female cervical lesions were tested for the presence of human papillomavirus (HPV) types 6/11,16/18 and 31/33/35 DNA using non-isotopic in situ hybridization. Specimens were classified according to the Bethesda System in low grade squamous intraepithelial lesion (LSIL), high grade SIL (HSIL) and squamous cell carcinoma (SCC). HPV prevalence ranged from 92.5% in LSIL to 68.5% in SCC. Benign types were prevalent in LSILs while oncogenic types infected predominantly HSILs and SCC. HPV infection showed to be age-dependent, but no significant relation to race has been detected. Patients were analyzed through a five-year period: 20.7% of the lesions spontaneously regressed while 48.9% persisted and 30.4% progressed to carcinoma. Patients submitted to treatment showed a 19.4% recurrence rate. High risk types were present in 78.6% (CrudeOR 13.8, P=0.0003) of the progressive lesions, and in 73.7% of the recurrent SILs (COR 19.3, P=0.0000001). Possible co-factors have also been evaluated: history of other sexually transmitted diseases showed to be positively related either to progression (Adjusted OR 13.0, P=0.0002) or to recurrence (AOR 17.2, P=0.0002) while oral contraceptive use and tobacco smoking were not significantly related to them (P>0.1). Association of two or more co-factors also proved to be related to both progression and recurrence, indicating that they may interact with HPV infection in order to increase the risk of developing malignant lesions.

An Adenovirus Vector Containing the Suicide Gene Thymidine Kinase for a Broad Application in Cancer Gene Therapy

Treatment of cancer using gene therapy is based on adding a property to the cell leading to its elimination. One possibility is the use of suicide genes that code for enzymes that transform a pro-drug into a cytotoxic product. The most extensively used is the herpes simplex virus thymidine kinase (TK) gene, followed by administration of the antiviral drug ganciclovir (GCV). The choice of the promoter to drive the transcription of a transgene is one of the determinants of a given transfer vector usefulness, as different promoters show different efficiencies depending on the target cell type. In the experiments presented here, we report the construction of a recombinant adenovirus carrying TK gene (Ad-TK) driven by three strong promoters (P CMV IE, SV40 and EN1) and its effectiveness in two cell types. Human HeLa and mouse CCR2 tumor cells were transduced with Ad-TK and efficiently killed after addition of GCV. We could detect two sizes of transcripts of TK gene, one derived from the close together P CMV IE/SV40 promoters and the other from the 1.5 Kb downstream EN1 promoter. The relative amounts of these transcripts were different in each cell type thus indicating a higher flexibility of this system.

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.

HPV vaccination: the beginning of the end of cervical cancer? - A Review

Human papillomavirus (HPV) is responsible for all cases of cervical cancer, as well as a great percentage of other anogenital tumors and oropharyngeal tumors. Since the main etiologic factor for these diseases is a virus, prophylactic measures are the best way to reduce the burden caused by the infection and associated disease. This review brings up to date information on the two commercially available prophylactic HPV vaccines against HPV, as well as presenting the ongoing research on HPV peptide, protein and dendritic cell based therapeutic vaccines.

Prostatic paracoccidioidomycosis: differential diagnosis of prostate cancer

Symptomatic prostatic paracoccidioidomycosis (PCM) is a very rare condition; however, it may express as a typical benign prostatic hyperplasia or a simulating prostatic adenocarcinoma. This case report presents PCM mimicking prostatic adenocarcinoma. The purpose of this paper is to call the general physician's attention to this important differential diagnosis.