Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08­6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)

Radiotherapy and collagenosis: is it safe? A case report of reirradiation in a patient with scleroderma

Historically, scleroderma and other collagenous diseases have been considered a relative contraindication to radiation. The literature has few studies describing poor outcomes and cosmesis in this situation and there are almost no data concerning about reirradiation and colagenosis. The authors describe a case of a patient with a soft tissue sarcoma in the arm submitted to conservative surgery. They describe the outcome, cosmesis and function of this rare twice-irradiated scleroderma patient.

Câncer colorretal / Colorectal cancer

O câncer colorretal se destaca entre as neoplasias malignas mais incidentes no Brasil e no mundo. Estratégias de rastreamento incluem a pesquisa de sangue oculto nas fezes ou a colonoscopia, aplicadas às populações sob maior risco. A sintomatologia é pouco específica e a colonoscopia é o método ideal para diagnóstico, sendo indicada sempre que houver sinais e sintomas intestinais. O estadiamento define as modalidades de tratamento e é direcionado para as vias mais comuns da disseminação da doença: linfática, hematogênica, contiguidade e implantes. Quando o diagnóstico se faz em estádios iniciais, o tratamento do câncer colorretal proporciona elevadas taxas de cura. Este artigo resume de forma esquemática as modalidades atuais de tratamento, estratificadas em função do estadiamento.

Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities

INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.

Mismatch repair genes in Lynch syndrome: a review: [review] / Genes de reparo de DNA na síndrome de Lynch: uma revisão: [revisão]

Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.

Familial adenomatous polyposis: data from the Hereditary Colorectal Cancer Registry (HCCR)

Family adenomatous polyposis (FAP) is a dominant autossomic disease responsible for nearly 1% of colorectal cancer (CRC) cases caused by mutations in gene APC and nearly complete penetrance. The identification of germinative mutations can be useful in the definition of the therapeutic conduct by means of the correlation genotype-phenotype. Objective: To describe clinical and molecular characteristics of families with FAP or attenuated FAP. Method: The study included families registered in the Hereditary Colorectal Cancer Registry of A.C.Camargo Hospital. Cancer records were registered and heredograms were created. Data were collected and stored in a database. Results: From 1992 to 2007 22 families were registered that had FAP, 16 with classic FAP, nine with Gardner Syndrome, and 6 with attenuated FAP. From 604 individuals, 120 had polyposis, 62 CRC, 10 desmoid tumors, three breast tumors, two tumors of the stomach, two thyroid tumors and one with prostate tumor. From 22 families, three were submitted to molecular analysis and mutations were identified in gene APC. Discussion: Half of the individuals presented CRC concomitant to polyposis, which can indicate a late diagnostic of the disease; three identified mutations presented correlations genotype-phenotype as predicted by the literature. Follow-up of patients with FAP, although they account for less than 1% of CRC cases, is vital for early cancer diagnosis.

P16 and p27 Immunohistochemical Expression in Colorectal Cancer: Analysis of 128 Patients

P16 and p27 are inhibiting proteins of cyclin-dependent kinases (CDKIs) that act in the restriction points of the cellular cycle, and it avoids its progression to DNA verification and repair by the cellular apparatus. This way, there should be, physiologically, an inverse relation between the expression of these proteins and cellular proliferation. However, what is really observed are changeable amounts of p27 in normal and tumor tissues. P16 participation in tumorigenesis is controversial. The expression of p16 and p27 as a prognostic factor in colorectal cancer (CRC) patients is controversial. Objetive: To establish a correlation between p16 and p27 immunohistochemical expressions with clinical and anatomopathological variable from patients with CRC. Material and methods: descriptive and retrospective study, with 128 CRC patients, treated surgically between 2000 and 2004, with available material for immunohistochemical analysis through standardized methods. The association between categorical variables was done using Chi-square, Pearson or Fisher?s Exact tests, and the continuous variables were analyzed by t-Student. Global survival and disease-free period were calculated according to Kaplan-Meier method and the associations through log-rank test. Results: The average follow-up time of patients was 35 months. Positivity of p16 was detected in 100% of cases. Negativity of p27 in 6.3% (n=8) of cases, with a significant association (p30.05) between p27 negative and tumors located in right colon (62.5%, n=5) and mucinous (62.5%, n=5). The average global survival was 54.8 months, and the significant clinical and pathological variables associated to survival were: better for curative surgeries; better for early stages; better for well-differentiated tumors; worse for cases with sanguineous or vascular lymphatic invasion; worse for perineural invasion. Conclusions: p27 negative is more frequent in right colon...

Number of Disected Lymph Nodes In Colorectal Cancer Patients SubmittedTo Radical Surgery: The Quality of Oncology Treatment

Introduction: the correct evaluation of lymph node disease influences the therapeutical decisions of colon and rectal cancer(CRC) patients. The number of dissected lymph nodes is a variable that have prognostic value and serves as an indicator of thequality of oncology treatment. For a correct evaluation of N stage to be accepted, the minimum number of dissected lymphnodes considered must be 12. In rectal cancer patients submitted to neoadjuvant radiochemotherapy, the interpretation of thenumber of dissected lymph nodes remains inconclusive. Objective: is to evaluate the number of dissected lymph nodes in CRCpatients submitted to curative surgery and determine this latter impact in oncologic treatment results. In cases of rectalcancer, to study the effect of neoadjuvant radiochemotherapy in dissected lymph nodes count. Method: in the period 1991-2004, 852 CRC patients were treated in Hospital A. C. Camargo . Patients with metastases at the time of diagnosis,synchronous and metachronic tumors, total colectomy or total proctocolectomy and hereditary colorectal cancer were excluded.The sample was constituted by 423 patients with sporadic colorectal adenocarcinoma who undergone curative radical surgery(168 colon primary tumors and 255 rectal tumors). Colon cancer patients, treated primarily by surgery, had also receivedadjuvant chemotherapy (5-FU) according to risk criteria. Rectal cancer patients with fixed or half-fixed injuries or clinicallycompromised lymph nodes (T3, T4 or N+) had received neoadjuvant radiochemotherapy, followed by surgery and chemotherapy(5-FU). Results: the median of the number of dissected lymph nodes in colon cancer patients was 17. In the case of rectalcancer patients, the median of dissected lymph nodes in the groups with and without neoadjuvant radiochemotherapy had beenrespectively 9 and 15 (p<0.001). 5-year specific survival rates for colon and rectal cancer patients were respectively...

Reconstruction of Urinary and Gastrointestinal Tracts in Patients Submitted to Pelvic Exenteration and Sphincter Preservation

Background and Objective: Reports in the literature regarding reconstruction of the lower urinary tract with orthotopic ilealneobladder post radical cystectomy for either non-transitional cell bladder tumors or other pelvic malignancies are rare. In suchcases, the reconstruction with orthotopic neobladder may represent a technical and therapeutic challenge, especially due topatients’ previous treatments like radiotherapy. To evaluate the feasibility and oncological results of the reconstruction ofurinary and gastrointestinal tracts in patients submitted to pelvic exenteration. Methods: From April 1995 to January 2004, 13patients with pelvic malignancies and non-transitional cell bladder tumors were submitted to pelvic exenteration. Bladderreconstruction was accomplished through orthotopic ileal neobladder in all cases. Seven patients had total pelvic exenterationwith anal sphincter-sparing procedure done as well as double-stapled colorectal anastomosis. Results: The mean age was 50years. In 6 patients late complications, such as hydronephrosis and urinary infection, were observed. No patient presented daytimeurinary incontinence after 6 months. During the follow-up period, no urethral recurrences were noted and all patientsremained with their functional neobladders. Two patients died of treatment-related causes and three died of cancer; sevenpatients are alive with no evidence of disease and one is alive with cancer. Overall and cancer-specific survival at 24 and 60months was 77.0% and 57%, respectively, and the mean of follow-up was 47% months (median 43 month). Conclusions:Urinary sphincter preservation and bladder reconstruction with orthotopic ileal neobladder with or without concomitant fecalsphincter preservation is a valuable option in patients with non-transitional cell bladder tumors or other pelvic malignancies thatrequire radical cystectomy for curative purposes.

Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy in the Treatment of Peritoneal Dissemination of Neoplasias: Preliminary Results with Closed Perfusion Technique

OBJECTIVE: to describe preliminary results ofcytoreductive surgery and intraperitoneal hyperthermicchemotherapy in the treatment of peritonealcarcinomatosis from a brazilian single institution.MATERIALS AND METHODS: a short cohort study wascarried out. 26 patients and 28 procedures wereperformed consecutively between March 2001 and June2005. 17 patients (65.4%) were treated for pseudomyxomaperitonei, 4 patients had mesothelioma, 2 carcinomatosisfrom colorectal cancer origin, 2 from ovary cancer and 1had peritoneal sarcomatosis. All cases were treated withclosed perfusion technique. The Completeness ofCytoreduction Score was used to classify the radicalityof the procedure and the NIH Commom Toxicity Criteriawas used to classify the complications. RESULTS: CC0and CC1 resections were achieved in 24 cases (85.7%).Grade 3 or 4 toxicity were observed in 5 cases (17.8%)and two patients died (7.1%). Severe complications weresignificant associated with the duration of surgery (morethan 10 hours). CONCLUSION: this radical treatment ofperitoneal carcinomatosis envolves high morbidity andmortality rates and must be conducted in referral centerswith multiprofessional teams and carefully selection ofpatients.

Hemipelvectomia interna alargada no tratamento de condrossarcoma pélvico localmente avançado: relato de caso / Extended internal hemipelvectomy for the treatment of locally advanced pelvic chondrosarcoma: a case report

É apresentado o caso de um paciente portador de condrossarcoma de baixo grau primário do osso ilíaco, com extensão para órgãos e estruturas adjacentes, tratado por hemipelvectomia interna alargada. São discutidos aspectos clínicos e abordagem terapêutica. O relato tem por finalidade ressaltar a importância da ressecção segundo princípios oncológicos, com preservação do membro, em pacientes que, face à extensão local, podem ser erradamente julgados como portadores de tumores irressecáveis.

Reconstrução com retalho miocutâneo anterior da coxa após hemipelvectomia por carcinoma de células escamosas de região glútea: relato de caso / Anterior thigh myocutaneous flap for reconstruction after external hemipelvectomy performed to treat a buttock squamous cell carcinoma: case report

Hemipelvectomia utilizando retalho miocutâneo anterior é indicada para tumores extensos da região glútea e parte posterior proximal da coxa. Um paciente do sexo masculino com 49 anos apresentou-se para tratamento de tumor ulcerado e infectado com crescimento progressivo há 3 anos em região glútea esquerda, originado de uma área de ulceração e cicatrização crônicas provocadas pela aplicação de múltiplas injeções de drogas ilícitas no local. O tumor infiltrava a pele, tecido celular subcutâneo e musculatura glútea, estando fixo ao osso ilíaco, articulação coxo-femural e trocanter maior. A tomografia computadorizada da pelve confirmou os achados do exame físico. A biópsia aberta foi realizada e revelou um carcinoma de células escamosas. Hemipelvectomia externa foi a opção escolhida para o tratamento. Um grande defeito foi criado após ressecção da extremidade inferior, hemipélvis e glúteo. Um retalho miocutâneo anterior do músculo quadríceps femural, adutores, sartório, pectíneo e grácil com pele e tecido celular subcutâneo sobrejacentes foi realizado. Os vasos femurais foram utilizados para manter o retalho viável. A recuperação pós-operatória aconteceu sem intercorrências e o retalho permaneceu totalmente viável. Alguns aspectos da técnica são apresentados.