Background and aim There is no consensus whether a colonoscopy should be recommended for patients... more Background and aim There is no consensus whether a colonoscopy should be recommended for patients under 50 years of age who present with both anal bleeding and benign anal diseases. The aim of this study is to evaluate the effectiveness of colonoscopy to detect neoplastic lesions in this specific group of patients. Methods A prospective study analyzing the results of colonoscopies performed in patients younger than 50 years of age who reported a rectal bleeding and also had a diagnosis of benign anal disease at first clinical visit. Results One hundred and eighty-seven consecutive patients were prospectively included in this study. In 35 patients (18.7%), adenomatous polyps were diagnosed. Thirty-seven percent of those lesions (13 cases) were further classified as either advanced adenomas or serrated adenomas. The prevalence of adenomas was 14.6% among patients under the age of 40 and 20% among those between 40 and 50 years of age. Thirty-one percent of the adenomas (11 cases) were located in the right colon, without any other concomitant lesion in the distal colon. In addition, an unsuspected case of sigmoid carcinoma was diagnosed. Conclusion The performance of colonoscopy in young patients with benign anal diseases and hematochezia resulted in a high rate of detection of neoplastic lesions. The method might be considered as a valid strategy of investigation in this frequent clinical situation.
Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most c... more Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx haplotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx haplotypes could have some protection to colorectal cancer. The hypothesis is not related with the presence of a special KIR gene and HLA ligand related to the disease, but to the presence of several activating genes in the individuals with no better action of one in relation to other. Further studies to confirm this observation are warranted.
Introdução: Paciente atendido no ambulatório da Coloproctologia com quadro de hidradenite supurat... more Introdução: Paciente atendido no ambulatório da Coloproctologia com quadro de hidradenite supurativa perianal extensa com 2 anos de evolução e com lesão ulcerada central associada à lesões satélites. Objetivos: Apresentar um caso de associação de carcinoma epidermóide em hidradenite supurativa. Material e Métodos: Realizada ressecção da lesão em novembro de 2011. Anatomo-patológico mostrou hidradenite supurativa com carcinoma epidermóide. Ressecção de nódulo pulmonar com equipe da cirurgia torácica em dezembro de 2010, que mostrou ser adenocarcinoma de pulmão. Apresenta surgimento de lesão ulcerada em local de cicatrização de lesão perianal prévia, durante consultas de revisão, com biópsia indicando carcinoma epidermóide. Atualmente, paciente em avaliaçãopré-operatória para ressecção de recidiva tumoral. Resultados e conclusões: Hidradenite supurativa é infecção bacteriana que ocorre produzindo obstrução e ruptura das glândulas apócrinas. Os sintomas e sinais são de longa duração e caracterizam-se por presença de abscessos e fístulas recidivantes, que, após cessada a fase inflamatória, deixam como seqüelas áreas de fibrose, orifícios fistulosos e escassa secreção purulenta. A associação de hidradenite supurativa com carcinoma epidermóide é rara, mesmo nos casos de doença inflamatóriade longa duração.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2003
To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas cl... more To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas classified according to Dukes staging. High-resolution imagery of 6,001 nuclei from 51 specimens of rectal carcinoma and 22 specimens of normal rectal tissue was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to form a characteristic signature. Rectal carcinomas were significantly different from normal rectum in their digital signature. Eleven karyometric features, such as nuclear area and total optical density, were clearly different between the groups, with significant differences found in analysis of 8 of those features. The most distinctive pattern in lesion signatures in comparison with normal rectal tissue was observed at Dukes' stage D. However, the highest average signature values were seen at Dukes' stage B. The lesion signatures and total optical density observed in cancer...
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2003
To investigate the prognostic value of nuclear features in rectal carcinoma. High-resolution imag... more To investigate the prognostic value of nuclear features in rectal carcinoma. High-resolution imagery of 3,635 nuclei from 51 patients operated on for rectal cancer at various Dukes' stages was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to derive a digital signature. Karyometric features were analyzed for correlation with progression of disease and death. Multivariate analysis of main karyometric features in comparison with cancer staging demonstrated that total optical density and clumpness, as well as average nuclear signature, had significant prognostic value in predicting cancer-related death. Digital signature seems to have a role as prognostic factor in rectal cancer. The method could be a useful parameter in deciding whether to perform adjuvant therapy in particular subgroups of patients, independently of tumor staging. However, these observations need to be substantiat...
TWIST1 gene, a transcription factor that belongs to the family of basic helix-loop-helix proteins... more TWIST1 gene, a transcription factor that belongs to the family of basic helix-loop-helix proteins, has been related to tumor progression and metastasis in different cancers. The aim of our study was to investigate TWIST1 promoter methylation in patients with primary colorectal carcinoma and determine its correlation with prognostic factors and disease outcome. Seventy-three patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as a control group. All tissues were analyzed through methylation-specific PCR. TWIST1 hypermethylation was detected in colorectal specimens of 46 patients with cancer, but in none of the tissues from the nonmalignant control group (p<0.001). In cancer patients, TWIST1 hypermethylation was found in 38 of 73 tumor samples as compared with 20 of 73 matched samples of non-cancerous colorectal tissue (P=0.001). TWIST1 hypermethylation was not correlated with prognostic predictors for the disease outcome, patients' overall survival and disease-free survival rates. We concluded that TWIST1 hypermethylation is present in the colon and rectum of most patients with colorectal carcinoma, suggesting this molecular alteration may be involved in the process of colorectal carcinogenesis.
A disseminação metastática endotraqueal e endobrônquica do câncer de cólon é um evento raro. Os a... more A disseminação metastática endotraqueal e endobrônquica do câncer de cólon é um evento raro. Os autores relatam o caso de um paciente com manifestação aguda de doença metastática endotraqueal e endobrônquica, 10 anos após o tratamento do tumor primário.
Background To assess the feasibility of the sentinel lymph node procedure in patients with rectal... more Background To assess the feasibility of the sentinel lymph node procedure in patients with rectal cancer extending to the anal canal. Methods Between January 2005 and April 2008, 15 patients with adenocarcinoma of the rectum with direct invasion of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel node procedure consisted of a combination of preoperative radiocolloid lymphoscintigraphy and intraoperative detection of the inguinal sentinel node with a gamma probe. Patent blue dye was also used to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylineosin staining and immunohistochemistry. Results Detection and removal of inguinal sentinel nodes was possible in all patients. Four patients (26.7%) had sentinel nodes identified as positive for metastatic adenocarcinoma. All positive cases also had metastases detected in perirectal lymph nodes; three of them developed hepatic or pulmonary metastases within 6 months after surgery. Of the 11 patients with negative sentinel nodes, only four (36.4%) also presented metastatic perirectal lymph nodes. Although none of the negative cases developed late inguinal metastases, three developed systemic or pelvic recurrence within 12 months after surgery. Conclusions The standardized procedure was highly effective in sampling inguinal sentinel nodes in very low rectal cancers, allowing the detection of subclinical metastatic disease. Although this technique can be potentially useful for a subgroup of patients with isolated inguinal metastases, it cannot be routinely recommended for patients with rectal tumors invading the anal canal at this moment.
In this letter, we report a case of a 57-year-old woman referred to our Coloproctology Division w... more In this letter, we report a case of a 57-year-old woman referred to our Coloproctology Division with symptoms of progressive constipation and a colonoscopy showing a rigid stenosis of the sigmoid colon, without any mucosal lesion. She had a history of a radical hysterectomy, performed 5 years earlier, due to a well-differentiated villoglandular cervical adenocarcinoma (Fig 1a). After a preoperative workup without additional findings, she underwent a sigmoid resection. Histopathologic examination of the surgical specimen revealed a well-differentiated glandular malignant tumor (3 9 3 cm) within the intestinal wall (Fig. 1b), without extension to the mucosal layer, but showing tumor emboli within subserosal vessels (Fig 1c). This glandular pattern was very similar to that previously seen in the cervical adenocarcinoma. Immunohistochemical analysis of the tumor confirmed the diagnosis of adenocarcinoma originating in the cervix. The immunohistochemical profile was as follows: strong intensity staining for CEA, CA125 and CK7 in 100 % of the tumor cells; strong staining for CK20 in 70 % of the cells; and negative staining for p53, k-ras and progesterone receptor. Considering the well-known etiological correlation of human papillomavirus (HPV) and cervical cancer, we decided to analyze tumor tissues through MY/GP-nested polymerase chain reaction (PCR) and through GP5?/ GP6? auto-nested PCR. Specific primer sets targeting the E6/E7 region of the HPVs 16, 18, 33, 45 were used for typing. The molecular analyses revealed the presence of HPV18 in both the primary cervical adenocarcinoma and the metastatic tumor. Metastatic lesions involving the colon are rare, being usually related to carcinomas of the breast and kidney or to melanoma. Colonic metastases of cervical cancers are exceedingly rare. To date, there are only 9 cases reported in the literature (eight squamous carcinomas) [1–5]. There is only one report of a cervical adenocarcinoma metastasizing to the large bowel, which also involved the sigmoid colon with extension to the subserosa [5]. HPV has been definitely implicated in the process of cervical carcinogenesis. Its role in development of primary colorectal cancer has also been demonstrated [6]. Some authors have reported the identification of HPV deoxyribonucleic acid (DNA) in bone, lung, liver and lymph node metastasis from squamous cell carcinoma of the cervix [4]. However, to the best of our knowledge, the present article is the first to report the detection of HPV within a metastastic adenocarcinoma of the cervix involving the colon. Our findings confirm the importance of HPV in cervical carcinogenesis and reinforce prior data indicating that viral integration into host cell DNA represents a crucial step for development of the malignant phenotype and tumor dissemination. A. P. Damin G. Agnes Laboratory of Molecular Biology, Federal University of Health Science of Porto Alegre, Porto Alegre, Brazil
Background Current guidelines recommend the assessment of at least 12 lymph nodes for rectal canc... more Background Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients. Methods An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained. Results On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P <0.001). In the chemoradiotherapy group, 29.6 % of patients had fewer than 12 lymph nodes obtained compared with 9.9 % in the primary surgery group (P 00.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not. Conclusions Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.
Background and aims: Metastatic spread of a distant tumor to the rectum is extremely rare. To our... more Background and aims: Metastatic spread of a distant tumor to the rectum is extremely rare. To our knowledge, there have been no published reports of hematogenic metastasis from a renal cell carcinoma to the rectum. Patients and methods: A patient with a renal cell carcinoma was initially treated by a radical right nephrectomy. Results: Nine months after the surgery he started to have multiple episodes of hematochezia. Colonoscopy showed a nodular lesion located in the distal rectum, and biopsy revealed an undifferentiated carcinoma. The patient then underwent abdominoperineal resection of the rectum, and histological examination showed metastatic renal clear cell carcinoma. Conclusion: This case represents an exceedingly rare condition, which has never been reported before.
European Journal of Surgical Oncology (EJSO), 2006
Aims: To review the studies investigating the efficacy of the sentinel lymph node (SLN) procedure... more Aims: To review the studies investigating the efficacy of the sentinel lymph node (SLN) procedure in anal canal carcinoma and to evaluate its potential role in guiding a more selective approach for patients with the malignancy. Methods: A literature search in the PubMed database was preformed using the key words 'sentinel lymph node' and 'anal cancer'. All indexed original articles (except case reports) on the SLN procedure in cancer of the anal canal were analysed. Results: There are five published series to date. Eighty-four patients were studied. Rates of SLN detection and removal ranged from 66 to 100% of patients investigated. Nodal metastases were found in 7.1 to 42% of cases. No serious complications were reported. Conclusions: The technique has proven to be safe and effective in sampling inguinal SLNs. The detection of occult metastases in clinically unsuspicious nodes represents an important improvement in the process of staging these patients, which has not been possible with any other method of diagnosis. Although SLN procedure is still in an early phase of investigation in this type of cancer, it emerges as an objective method to guide individual therapeutic decisions.
This study was conducted to assess the feasibility of the sentinel lymph node procedure in patien... more This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal. Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3). Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal. The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.
Background RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified a... more Background RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified as a candidate compound for the treatment of tumor necrosis factor (TNF)-dependent chronic inflammatory conditions. Aim The aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis. Methods Ninety Wistar rats were included in the study. Colitis was induced by a single intracolonic application of acetic acid. Rats were divided into three groups of treatment: subcutaneous RC-3095, intracolonic mesalazine, and subcutaneous dexamethasone. Additionally, there was a fourth group of animals submitted to induction of colitis without receiving any form of treatment, and a fifth group in which no colitis was induced. Seventy-two hours after instillation of acetic acid, the animals were killed and the following parameters were assessed: morphological score of damage, histological score of colonic inflammation, and immunohistochemical expression of TNF-a and interleukin (IL)-1b. Results RC-3095 was the only treatment to significantly reduce macroscopic and microscopic scores of inflammation as compared with the animals from the non-treated colitis group. RC-3095 also significantly reduced the colonic expression of TNF-a, but not the expression of IL-1b. Conclusions RC-3095 reduced the colitis severity in a well-established experimental model of IBD. The antiinflammatory activity of this compound was associated with a reduction in the colonic expression of TNF-a. These results suggest that interference with GRP pathway might represent a potential new strategy for the treatment of ulcerative colitis that deserves further investigational studies.
Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a... more Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. Methods: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Results: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. Discussion: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.
Background and aim There is no consensus whether a colonoscopy should be recommended for patients... more Background and aim There is no consensus whether a colonoscopy should be recommended for patients under 50 years of age who present with both anal bleeding and benign anal diseases. The aim of this study is to evaluate the effectiveness of colonoscopy to detect neoplastic lesions in this specific group of patients. Methods A prospective study analyzing the results of colonoscopies performed in patients younger than 50 years of age who reported a rectal bleeding and also had a diagnosis of benign anal disease at first clinical visit. Results One hundred and eighty-seven consecutive patients were prospectively included in this study. In 35 patients (18.7%), adenomatous polyps were diagnosed. Thirty-seven percent of those lesions (13 cases) were further classified as either advanced adenomas or serrated adenomas. The prevalence of adenomas was 14.6% among patients under the age of 40 and 20% among those between 40 and 50 years of age. Thirty-one percent of the adenomas (11 cases) were located in the right colon, without any other concomitant lesion in the distal colon. In addition, an unsuspected case of sigmoid carcinoma was diagnosed. Conclusion The performance of colonoscopy in young patients with benign anal diseases and hematochezia resulted in a high rate of detection of neoplastic lesions. The method might be considered as a valid strategy of investigation in this frequent clinical situation.
Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most c... more Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx haplotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx haplotypes could have some protection to colorectal cancer. The hypothesis is not related with the presence of a special KIR gene and HLA ligand related to the disease, but to the presence of several activating genes in the individuals with no better action of one in relation to other. Further studies to confirm this observation are warranted.
Introdução: Paciente atendido no ambulatório da Coloproctologia com quadro de hidradenite supurat... more Introdução: Paciente atendido no ambulatório da Coloproctologia com quadro de hidradenite supurativa perianal extensa com 2 anos de evolução e com lesão ulcerada central associada à lesões satélites. Objetivos: Apresentar um caso de associação de carcinoma epidermóide em hidradenite supurativa. Material e Métodos: Realizada ressecção da lesão em novembro de 2011. Anatomo-patológico mostrou hidradenite supurativa com carcinoma epidermóide. Ressecção de nódulo pulmonar com equipe da cirurgia torácica em dezembro de 2010, que mostrou ser adenocarcinoma de pulmão. Apresenta surgimento de lesão ulcerada em local de cicatrização de lesão perianal prévia, durante consultas de revisão, com biópsia indicando carcinoma epidermóide. Atualmente, paciente em avaliaçãopré-operatória para ressecção de recidiva tumoral. Resultados e conclusões: Hidradenite supurativa é infecção bacteriana que ocorre produzindo obstrução e ruptura das glândulas apócrinas. Os sintomas e sinais são de longa duração e caracterizam-se por presença de abscessos e fístulas recidivantes, que, após cessada a fase inflamatória, deixam como seqüelas áreas de fibrose, orifícios fistulosos e escassa secreção purulenta. A associação de hidradenite supurativa com carcinoma epidermóide é rara, mesmo nos casos de doença inflamatóriade longa duração.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2003
To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas cl... more To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas classified according to Dukes staging. High-resolution imagery of 6,001 nuclei from 51 specimens of rectal carcinoma and 22 specimens of normal rectal tissue was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to form a characteristic signature. Rectal carcinomas were significantly different from normal rectum in their digital signature. Eleven karyometric features, such as nuclear area and total optical density, were clearly different between the groups, with significant differences found in analysis of 8 of those features. The most distinctive pattern in lesion signatures in comparison with normal rectal tissue was observed at Dukes' stage D. However, the highest average signature values were seen at Dukes' stage B. The lesion signatures and total optical density observed in cancer...
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2003
To investigate the prognostic value of nuclear features in rectal carcinoma. High-resolution imag... more To investigate the prognostic value of nuclear features in rectal carcinoma. High-resolution imagery of 3,635 nuclei from 51 patients operated on for rectal cancer at various Dukes' stages was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to derive a digital signature. Karyometric features were analyzed for correlation with progression of disease and death. Multivariate analysis of main karyometric features in comparison with cancer staging demonstrated that total optical density and clumpness, as well as average nuclear signature, had significant prognostic value in predicting cancer-related death. Digital signature seems to have a role as prognostic factor in rectal cancer. The method could be a useful parameter in deciding whether to perform adjuvant therapy in particular subgroups of patients, independently of tumor staging. However, these observations need to be substantiat...
TWIST1 gene, a transcription factor that belongs to the family of basic helix-loop-helix proteins... more TWIST1 gene, a transcription factor that belongs to the family of basic helix-loop-helix proteins, has been related to tumor progression and metastasis in different cancers. The aim of our study was to investigate TWIST1 promoter methylation in patients with primary colorectal carcinoma and determine its correlation with prognostic factors and disease outcome. Seventy-three patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as a control group. All tissues were analyzed through methylation-specific PCR. TWIST1 hypermethylation was detected in colorectal specimens of 46 patients with cancer, but in none of the tissues from the nonmalignant control group (p<0.001). In cancer patients, TWIST1 hypermethylation was found in 38 of 73 tumor samples as compared with 20 of 73 matched samples of non-cancerous colorectal tissue (P=0.001). TWIST1 hypermethylation was not correlated with prognostic predictors for the disease outcome, patients' overall survival and disease-free survival rates. We concluded that TWIST1 hypermethylation is present in the colon and rectum of most patients with colorectal carcinoma, suggesting this molecular alteration may be involved in the process of colorectal carcinogenesis.
A disseminação metastática endotraqueal e endobrônquica do câncer de cólon é um evento raro. Os a... more A disseminação metastática endotraqueal e endobrônquica do câncer de cólon é um evento raro. Os autores relatam o caso de um paciente com manifestação aguda de doença metastática endotraqueal e endobrônquica, 10 anos após o tratamento do tumor primário.
Background To assess the feasibility of the sentinel lymph node procedure in patients with rectal... more Background To assess the feasibility of the sentinel lymph node procedure in patients with rectal cancer extending to the anal canal. Methods Between January 2005 and April 2008, 15 patients with adenocarcinoma of the rectum with direct invasion of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel node procedure consisted of a combination of preoperative radiocolloid lymphoscintigraphy and intraoperative detection of the inguinal sentinel node with a gamma probe. Patent blue dye was also used to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylineosin staining and immunohistochemistry. Results Detection and removal of inguinal sentinel nodes was possible in all patients. Four patients (26.7%) had sentinel nodes identified as positive for metastatic adenocarcinoma. All positive cases also had metastases detected in perirectal lymph nodes; three of them developed hepatic or pulmonary metastases within 6 months after surgery. Of the 11 patients with negative sentinel nodes, only four (36.4%) also presented metastatic perirectal lymph nodes. Although none of the negative cases developed late inguinal metastases, three developed systemic or pelvic recurrence within 12 months after surgery. Conclusions The standardized procedure was highly effective in sampling inguinal sentinel nodes in very low rectal cancers, allowing the detection of subclinical metastatic disease. Although this technique can be potentially useful for a subgroup of patients with isolated inguinal metastases, it cannot be routinely recommended for patients with rectal tumors invading the anal canal at this moment.
In this letter, we report a case of a 57-year-old woman referred to our Coloproctology Division w... more In this letter, we report a case of a 57-year-old woman referred to our Coloproctology Division with symptoms of progressive constipation and a colonoscopy showing a rigid stenosis of the sigmoid colon, without any mucosal lesion. She had a history of a radical hysterectomy, performed 5 years earlier, due to a well-differentiated villoglandular cervical adenocarcinoma (Fig 1a). After a preoperative workup without additional findings, she underwent a sigmoid resection. Histopathologic examination of the surgical specimen revealed a well-differentiated glandular malignant tumor (3 9 3 cm) within the intestinal wall (Fig. 1b), without extension to the mucosal layer, but showing tumor emboli within subserosal vessels (Fig 1c). This glandular pattern was very similar to that previously seen in the cervical adenocarcinoma. Immunohistochemical analysis of the tumor confirmed the diagnosis of adenocarcinoma originating in the cervix. The immunohistochemical profile was as follows: strong intensity staining for CEA, CA125 and CK7 in 100 % of the tumor cells; strong staining for CK20 in 70 % of the cells; and negative staining for p53, k-ras and progesterone receptor. Considering the well-known etiological correlation of human papillomavirus (HPV) and cervical cancer, we decided to analyze tumor tissues through MY/GP-nested polymerase chain reaction (PCR) and through GP5?/ GP6? auto-nested PCR. Specific primer sets targeting the E6/E7 region of the HPVs 16, 18, 33, 45 were used for typing. The molecular analyses revealed the presence of HPV18 in both the primary cervical adenocarcinoma and the metastatic tumor. Metastatic lesions involving the colon are rare, being usually related to carcinomas of the breast and kidney or to melanoma. Colonic metastases of cervical cancers are exceedingly rare. To date, there are only 9 cases reported in the literature (eight squamous carcinomas) [1–5]. There is only one report of a cervical adenocarcinoma metastasizing to the large bowel, which also involved the sigmoid colon with extension to the subserosa [5]. HPV has been definitely implicated in the process of cervical carcinogenesis. Its role in development of primary colorectal cancer has also been demonstrated [6]. Some authors have reported the identification of HPV deoxyribonucleic acid (DNA) in bone, lung, liver and lymph node metastasis from squamous cell carcinoma of the cervix [4]. However, to the best of our knowledge, the present article is the first to report the detection of HPV within a metastastic adenocarcinoma of the cervix involving the colon. Our findings confirm the importance of HPV in cervical carcinogenesis and reinforce prior data indicating that viral integration into host cell DNA represents a crucial step for development of the malignant phenotype and tumor dissemination. A. P. Damin G. Agnes Laboratory of Molecular Biology, Federal University of Health Science of Porto Alegre, Porto Alegre, Brazil
Background Current guidelines recommend the assessment of at least 12 lymph nodes for rectal canc... more Background Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients. Methods An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained. Results On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P <0.001). In the chemoradiotherapy group, 29.6 % of patients had fewer than 12 lymph nodes obtained compared with 9.9 % in the primary surgery group (P 00.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not. Conclusions Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.
Background and aims: Metastatic spread of a distant tumor to the rectum is extremely rare. To our... more Background and aims: Metastatic spread of a distant tumor to the rectum is extremely rare. To our knowledge, there have been no published reports of hematogenic metastasis from a renal cell carcinoma to the rectum. Patients and methods: A patient with a renal cell carcinoma was initially treated by a radical right nephrectomy. Results: Nine months after the surgery he started to have multiple episodes of hematochezia. Colonoscopy showed a nodular lesion located in the distal rectum, and biopsy revealed an undifferentiated carcinoma. The patient then underwent abdominoperineal resection of the rectum, and histological examination showed metastatic renal clear cell carcinoma. Conclusion: This case represents an exceedingly rare condition, which has never been reported before.
European Journal of Surgical Oncology (EJSO), 2006
Aims: To review the studies investigating the efficacy of the sentinel lymph node (SLN) procedure... more Aims: To review the studies investigating the efficacy of the sentinel lymph node (SLN) procedure in anal canal carcinoma and to evaluate its potential role in guiding a more selective approach for patients with the malignancy. Methods: A literature search in the PubMed database was preformed using the key words 'sentinel lymph node' and 'anal cancer'. All indexed original articles (except case reports) on the SLN procedure in cancer of the anal canal were analysed. Results: There are five published series to date. Eighty-four patients were studied. Rates of SLN detection and removal ranged from 66 to 100% of patients investigated. Nodal metastases were found in 7.1 to 42% of cases. No serious complications were reported. Conclusions: The technique has proven to be safe and effective in sampling inguinal SLNs. The detection of occult metastases in clinically unsuspicious nodes represents an important improvement in the process of staging these patients, which has not been possible with any other method of diagnosis. Although SLN procedure is still in an early phase of investigation in this type of cancer, it emerges as an objective method to guide individual therapeutic decisions.
This study was conducted to assess the feasibility of the sentinel lymph node procedure in patien... more This study was conducted to assess the feasibility of the sentinel lymph node procedure in patients with epidermoid carcinoma of the anal canal. Between February 2001 and November 2002, 14 patients with epidermoid carcinoma of the anal canal and no clinical evidence of inguinal involvement were prospectively enrolled in the study. The sentinel lymph node procedure consisted of a combination of preoperative lymphoscintigraphy with technetium 99m dextran 500 injected around the tumor and intraoperative detection of the sentinel node with a gamma probe. Patent blue V dye was also injected at the periphery of the tumor to facilitate direct identification of the blue-stained lymph node. After removal, the sentinel node was studied by hematoxylin and eosin staining and immunohistochemistry for pancytokeratins (antigen A1 and A3). Detection and removal of sentinel lymph nodes was possible in all patients. There was no correlation between tumor size and pattern of lymphatic drainage to the groin. Tumors located in the midline of the anal canal gave rise to bilateral sentinel nodes in eight of nine cases. In total, 23 sentinel lymph nodes were removed. One patient (7.1 percent) had a node identified as positive for metastatic carcinoma on immunohistochemical staining. Surgical complications were minimal. The standardized technique was safe and highly effective in sampling inguinal sentinel lymph nodes in carcinoma of the anal canal. It also proved to be useful as an instrument to detect micrometastatic deposits in clinically normal nodes. Our early results suggest the sentinel lymph node procedure may have a role in guiding a more selective approach for patients with anal cancer. Additional studies in a larger patient population to determine the sensitivity and specificity of this method are warranted.
Background RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified a... more Background RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified as a candidate compound for the treatment of tumor necrosis factor (TNF)-dependent chronic inflammatory conditions. Aim The aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis. Methods Ninety Wistar rats were included in the study. Colitis was induced by a single intracolonic application of acetic acid. Rats were divided into three groups of treatment: subcutaneous RC-3095, intracolonic mesalazine, and subcutaneous dexamethasone. Additionally, there was a fourth group of animals submitted to induction of colitis without receiving any form of treatment, and a fifth group in which no colitis was induced. Seventy-two hours after instillation of acetic acid, the animals were killed and the following parameters were assessed: morphological score of damage, histological score of colonic inflammation, and immunohistochemical expression of TNF-a and interleukin (IL)-1b. Results RC-3095 was the only treatment to significantly reduce macroscopic and microscopic scores of inflammation as compared with the animals from the non-treated colitis group. RC-3095 also significantly reduced the colonic expression of TNF-a, but not the expression of IL-1b. Conclusions RC-3095 reduced the colitis severity in a well-established experimental model of IBD. The antiinflammatory activity of this compound was associated with a reduction in the colonic expression of TNF-a. These results suggest that interference with GRP pathway might represent a potential new strategy for the treatment of ulcerative colitis that deserves further investigational studies.
Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a... more Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. Methods: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Results: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. Discussion: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.
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Papers by Daniel Damin