Fragmented pattern of tumor regression and lateral intramural spread may influence margin appropriateness after TEM for rectal cancer following neoadjuvant CRT.

BACKGROUND: The main tenets of local excision of rectal cancer following neoadjuvant chemoradiation (CRT) are that the mucosal scar represents the main focus of residual disease and a solid conglomerate around this rather than being scattered (fragmented) through the bowel wall. METHODS: Retrospective review of a prospective cohort of patients with residual rectal ycT1-2N0 adenocarcinoma with small residual tumors (≤3 cm) following CRT who underwent transanal endoscopic microsurgery (TEM) with 1-cm margins around the residual mucosal abnormality was performed. Distribution and morphology (solid vs. fragmented) of tumor spread were studied and correlated to postoperative oncological outcomes. RESULTS: Thirty patients were included. Twenty percent (n = 6) were ypT1, 60% (n = 18) were ypT2, and 20% (n = 6) were ypT3 tumors. Fragmentation was present in 37%. The mean distance between foci of residual scattered tumor was 3.6 ± 2.0 mm. Lateral spread under normal mucosa was present in 19 specimens (53%; mean extension 4.8 ± 2.4 mm). With a median follow up of 32 months, none of these findings impacted upon development of recurrence. CONCLUSIONS: Both occult lateral spread and fragmented tumor patterns are common findings after CRT. Despite the potential of occult spread to mislead surgeon choice of resection margin, its presence did not influence oncological outcome in this series.

Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis.

OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p>0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis

OBJECTIVE: Many changes in mucosal morphology are observed following ileal pouch construction, including colonic metaplasia and dysplasia. Additionally, one rare but potential complication is the development of adenocarcinoma of the reservoir. The aim of this study was to evaluate the most frequently observed histopathological changes in ileal pouches and to correlate these changes with potential risk factors for complications. METHODS: A total of 41 patients were enrolled in the study and divided into the following three groups: a non-pouchitis group (group 1) (n = 20; 8 males; mean age: 47.5 years) demonstrating optimal outcome; a pouchitis without antibiotics group (group 2) (n = 14; 4 males; mean age: 47 years), containing individuals with pouchitis who did not receive treatment with antibiotics; and a pouchitis plus antibiotics group (group 3) (n = 7; 3 males; mean age: 41 years), containing those patients with pouchitis who were administered antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15 (36.6%) of the 41 patients evaluated; of these, five (25%) were from group 1, eight (57.1%) were from group 2, and two (28.6%) were from group 3. However, no correlation was established between the presence of metaplasia and pouchitis (p = 0.17). and no differences in mucosal atrophy or the degree of chronic or acute inflammation were observed between groups 1, 2, and 3 (p>0.45). Moreover, no dysplasia or neoplastic changes were detected. However, the degree of mucosal atrophy correlated well with the time of postoperative follow-up (p = 0.05). CONCLUSIONS: The degree of mucosal atrophy, the presence of colonic metaplasia, and the degree of acute or chronic inflammation do not appear to constitute risk factors for the development of pouchitis. Moreover, we observed that longer postoperative follow-up times were associated with greater degrees of mucosal atrophy.

Reduced population of interstitial cells of Cajal in Chagasic megacolon.

BACKGROUND/AIMS: In Chagasic megacolon, there is a reduction in the population of interstitial cells of Cajal. It was aimed to evaluate density of Cajal cells in the resected colon of Chagasic patients compared to control patients and to verify possible association between preoperative and postoperative bowel function of megacolon patients and cell count. METHODOLOGY: Sixteen megacolon patients (12 female; mean age 54.4 (31-73)) were operated on. Pre- and postoperative evaluation using Cleveland clinic constipation score was undertaken. Resected colons were examined. Cajal cells were identified by immunohistochemistry (anti-CD117). The mean cell number was compared to resected colons from 16 patients (7 female; mean age 62.8 (23-84)) with non-obstructive sigmoid cancer. Association between pre- and postoperative constipation scores and cell count for megacolon patients was evaluated using the Pearson test (r). RESULTS: A reduced number of Cajal cells (per field: 2.84 (0-6.6) vs. 9.68 (4.3-13); p<0.001) were observed in the bowel of megacolon patients compared to cancer patients. No correlation between constipation score before (r=- 0.205; p=0.45) or after surgery (r=0.291; p=0.28) and cell count in megacolon was observed. CONCLUSIONS: Patients with megacolon display marked reduction of interstitial cells of Cajal. An association of constipation severity and Cajal cells depopulation was not demonstrated.

Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery? / Depleção de células intersticiais de Cajal no megacólon chagásico: a caminho do tratamento cirúrgico individualizado?

BACKGROUND: The mechanism of constipation in patients with Chagasic megacolon remains partially explained. In these patients, it was recently demonstrated a reduction in the population of interstitial cells of Cajal. AIM: To evaluate density of Cajal cells in the surgically resected colon of Chagasic patients in comparison to control patients, and to verify possible association between preoperative and postoperative bowel function of Chagasic patients and colonic cell count. METHOD: Sixteen patients with Chagasic megacolon were operated on. Clinical pre- and post-operative evaluation using the Cleveland Clinic Constipation Score was undertaken. Resected colons were examined. Cajal cells were identified by immunohistochemistry using anti-CD117 antibody. The mean cell number was compared to resected colons from 16 patients with non-obstructive sigmoid cancer. Association between pre-and post-operative constipation scores and cell count for megacolon patients was evaluated using the Pearson coefficient correlation test (r). RESULTS: A reduced number of Cajal cells [cells per field: 2.84 (0-6.6) vs. 9.68 (4.3-13) - p<0.001] was observed in the resected colon of Chagasic patients when compared to colon cancer patients. No correlation between constipation score before (r=-0.205; p=0.45) or after surgery (r=0,291; p=0.28) and cell count for megacolon patients was observed. CONCLUSIONS: Patients with Chagasic megacolon display marked reduction of interstitial cells of Cajal when compared to non-Chagasic patients. An association of constipation severity and Cajal cells depopulation in Chagasic megacolon could not be demonstrated.

RACIONAL: A fisiopatologia da constipação intestinal nos pacientes portadores de megacólon chagásico permanece parcialmente esclarecida. Recentemente demontrou-se que nesses pacientes, o contingente de células intersticiais de Cajal está reduzido assim como ocorre em outros distúrbios funcionais gastrointestinais. OBJETIVO: Avaliar a densidade de células intersticiais de Cajal no intestino ressecado de pacientes submetidos a tratamento cirúrgico eletivo de megacólon chagásico em comparação com a observada no cólon de pacientes controles, e verificar possível associação entre o grau de constipação intestinal de pacientes com megacólon chagásico no pré e no pós-operatório e o grau de despopulação de células de Cajal. MÉTODO: Dezesseis pacientes com megacólon chagásico foram operados. A avaliação da função intestinal através do escore de constipação da Cleveland Clinic foi registrada antes e após a operação. O espécime cirúrgico foi examinado e as células de Cajal foram identificadas pela técnica imunoistoquímica empregando o anticorpo anti-CD117 (c-kit). O número médio de células de Cajal nos megacólons foi comparado com o de cólons ressecados de 16 pacientes [7 mulheres; média de idade de 62,8 (23-84)] operados de câncer não-obstrutivo do sigmóide. A associação entre o escore de constipação no pré e no pós-operatório e a contagem de células de Cajal foi medida através do coeficente de correlação de Pearson (r). RESULTADOS: Redução significativa no número de células de Cajal (células por campo de 400X: 2,84 (0-6,6) vs. 9,68 (4,3-13) - ] foi observada nos megacólons quando comparados ao espécime de pacientes operados por câncer. Não foi observada associação entre o escore de constipação pré (r=-0.205; p=0.45) ou pós-operatório (r=0,291; p=0.28) a a contagem de células de Cajal para os pacientes com megacólon. CONCLUSÕES: Pacientes com megacólon chagásico exibem acentuada redução no número de células intersticiais de Cajal no intestino grosso...

Lymph node size in rectal cancer following neoadjuvant chemoradiation--can we rely on radiologic nodal staging after chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

Mucinous colorectal adenocarcinoma: influence of mucin expression (Muc1, 2 and 5) on clinico-pathological features and prognosis.

BACKGROUND: Mucinous component is associated with distinct clinical and pathological features and poor survival in colorectal cancer. The purpose of this study was to determine differences in outcomes of patients with mucinous colorectal adenocarcinoma according to the type of mucin expressed. MATERIALS AND METHODS: Immunohistochemistry was performed in all tumors of patients who underwent radical surgery between 1998 and 2003 with mucinous colorectal cancer using antibodies against MUC1, 2, and 5. Correlation between immunoexpression and clinical, pathological features and survival was performed. RESULTS: Of the 418 patients treated in this period, only 35 had a mucinous adenocarcinoma. Of these, 25 were positive for 1 or more mucin expression. MUC2 expression correlated with tumor site and depth of penetration, while MUC5 expression correlated to tumor site. Overall survival was significantly worse for patients with MUC2 expression, and disease-free survival was significantly worse for patients with MUC1 expression. CONCLUSIONS: Mucin expression may have significant correlation to specific clinical-pathological features and survival of patients with mucinous-type colorectal adenocarcinoma. These differences may reflect distinct molecular mechanisms involved in carcinogenesis of mucinous colorectal adenocarcinoma.

Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean?

PURPOSE: The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. METHODS: Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. RESULTS: Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P<0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P=0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P=0.2), and both were significantly better than patients with ypN+ disease (30 percent; P<0.001). CONCLUSIONS: Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.

Análise de fatores clínicos e histopatológicos em metástases hepáticas de adenocarcinoma colorretal / Analysis of clinical and histopathological factors in adenocarcinoma colorectal cancer liver metastases

RACIONAL: O câncer colorretal inclui-se entre as primeiras neoplasias malignas mais freqüentes no mundo e causa de morte entre os diversos tipos de câncer; ultrapassado somente pelo câncer de pulmão. Freqüentemente ocorrem metástases e o agravamento da doença levando à morte OBJETIVO: Avaliar se a ressecção cirúrgica radical das metástases hepáticas com margem de segurança superior a 10 mm promove maiores índices de sobrevivência e quais os fatores que podem auxiliar no prognóstico. MÉTODOS: Análise retrospectiva de 49 pacientes portadores de metástase hepática de adenocarcinoma colorretal, sem evidência de concomitância em outros órgãos e submetidos a tratamento cirúrgico. Os indicadores epidemiológicos foram: idade, gênero, tamanho da metástase hepática e ou da maior lesão, número de nódulos regionais ressecados e comprometidos, margem de ressecção livre de neoplasia. Os sobreviventes foram convocados e avaliados clinicamente, por meio de exames laboratoriais e estudos radiológicos com finalidade de determinar a evolução da doença. Os critérios de exclusão foram falta de comprovação histológica da metástase hepática e com evidência de neoplasia em outros órgãos além do intestino grosso e do fígado, na época do tratamento cirúrgico inicial e da metástase hepática. RESULTADOS: A casuística consistiu de 24 pacientes do gênero feminino e 25 do masculino.A média e o desvio-padrão das idades foi de 55,9 + 11,9 anos com mediana de 56 anos, Foram realizadas 15 hepatectomias direitas regradas e 11 esquerdas; 13 segmentectomias direitas e esquerdas; 9 nodulectomias e 1 biópsia. Adicionalmente efetuaram-se 2 alcoolizações, 4 quimioembolizações, 1 termoablação, 1 bloqueio portal seletivo com posterior hepatectomia direita e termoablação de lesões no segmentos III e IV. O peso do fígado foi igual a 555,71 + 261,96 g e mediana de 600 g. O número mediano de nódulos ressecados foi de 2. O tamanho médio da lesão foi de 4,45 + 2,8. A margem cirúrgica maior que 10 mm foi observada em 32 casos. O valor do CEA antes da operação de 68,13 + 105,65 ng/ml e mediana de 22,2 ng/ml. Obito ocorreu em 22 casos (44,89%). O tipo histológico predominante foi o adenocarcinoma tubular moderadamente diferenciado em 65,96%, 17,02% pouco e 17,02% bem diferenciado. Fatores como o tipo histológico indiferenciado, menor infiltrado inflamatório peritumoral, maior reação desmoplásica e inexistência de cápsula circunscrevendo o tumor parecem compor fatores de pior prognóstico, embora não tenham sido capazes de isoladamente serem significantes Observou-se associação significante entre o nível sérico abaixo de 7 ng/ml de CEA e o sincronismo da metástase hepática. CONCLUSÕES: A ressecção cirúrgica radical das metástases hepáticas com margem de segurança superior a 10 mm promoveram maior sobrevida; os níveis séricos elevados de CEA associaram-se à recidiva tumoral das metástases e pior evolução clínica; 3. tipo histológico indiferenciado, menor infiltrado inflamatório peritumoral, maior reação desmoplásica, inexistência de cápsula circunscrevendo o tumor sugerem pior prognóstico.

BACKGROUND: Colorectal cancer belongs to the most frequent malignant neoplasia in the world and responsible for the cause of death among other types of cancer; ranked second behind lung cancer. Metastasis frequently occurs and disease worsening leads to patient death. AIM: To analyze if radical surgical resection for colorectal cancer liver metastases with resection margin greater than 10 mm promotes better survival rates and the factors that might predict prognosis. METHODS: Retrospective analysis of 49 patients presenting colorectal adenocarcinoma liver metastases without evidence of concomitant disease and submitted to surgical treatment. Epidemiologic parameters were: age, gender, size of liver metastasis and or the largest lesion, number of regional lymph nodes dissection and involvement, neoplasia-free margin resection. Patients were evaluated clinically, undergoing laboratory exams analysis and imaging studies for disease follow-up. Exclusion criteria were non-histological proof of liver metastasis and evidence of disease in sites other than colon and liver, at the time of surgical treatment and liver metastasis. RESULTS: Casuistic group consisted of 24 female and 25 male patients. Mean and standard deviation for age was 55,9 + 11,9 years, median of 56 years. Surgical procedures included 15 right hepatectomy and 11 left hepatectomy; 13 right and left segmentectomy; 9 nodulectomy and 1 biopsy. Additionally, 2 alcoholization, 4 chemoembolization, 1 thermoablative therapy, 1 selective portal vein block with later right hepatectomy and thermoablative thereapy on segments III and IV were performed. Liver weighted 555,71 + 261,96 g, median of 600g. Median of lymph nodes resection was 2. The mean lesion size consisted in 4,45 + 2,8. Resection margin greater than 10 mm was observed in 32 cases. Serum CEA value before surgical procedure was 68,13 + 105,65 ng/ml, median of 22,2 ng/ml. Death occurred in 22 cases (44,89%). Predominant histological diagnoses was moderate differentiated tubular adenocarcinoma in 65,96%, 17,02% poorly and 17,02% well differentiated. Factors such as undifferentiated histological type, less inflammatory peritumor infiltration, greater desmoplastic reaction and the absence of capsule around the tumor seem to reflect worse prognosis, although none of the factors being statistic significantly isolated. Significant association was noticed between CEA serum level under 7 ng/mg and synchronic hepatic metastases. CONCLUSION: Radical surgical resection for colorectal cancer liver metastases with a resection margin greater than 10 mm promotes better survival rates; elevated serum CEA levels were related to recurrence after hepatic resection for metastatic colorectal cancer and worse clinical outcome; undifferentiated histological type, less inflammatory peritumor infiltration, greater desmoplastic reaction and the absence of capsule around the tumor suggested worse prognosis.

Peritumoral inflammatory infiltrate is not a prognostic factor in distal rectal cancer following neoadjuvant chemoradiation therapy.

BACKGROUND: Peritumoral inflammatory response has been considered a good prognostic factor for colorectal cancer. However, this has not been evaluated in patients submitted to neoadjuvant therapy for distal rectal cancer. For this reason, we decided to study the effect of the presence of this pathological finding on disease recurrence and survival. METHODS: The peritumoral inflammatory infiltrate from recovered pathological specimens of patients operated after neoadjuvant therapy for distal rectal cancer was graded (positive or negative). Patients were compared according to the presence of peritumoral inflammatory response. RESULTS: Of the 168 patients, 63 (37%) patients had a peritumoral inflammatory response. The lack of peritumoral inflammatory response was significantly associated with the presence of mucinous component (13 vs 3%; p = 0.02). Five-year overall survival (91 vs 81%) and disease-free survival (57 vs 48%) were not significantly different between patients with and without peritumoral inflammatory response (p = 0.5 and 0.3, respectively). CONCLUSIONS: Peritumoral inflammatory response is not a favorable prognostic factor in patients with distal rectal cancer after neoadjuvant chemoradiation therapy. Possibly, the immunosuppressive action of chemoradiation therapy may lead to a loss of function of the immunological response, which may represent a disadvantage of the neoadjuvant approach for the management of distal rectal cancer.

Full-thickness chest wall resection for recurrent breast phyllodes tumor.

Phyllodes tumor is a rare breast neoplasm. We present the case of a woman who underwent multiple surgical procedures for phyllodes tumor treatment. Even after bilateral mastectomy and radiotherapy, local recurrences developed. We performed a full-thickness chest wall resection with wide margins, a procedure rarely reported in medical literature for this purpose. Only after this approach did we obtain disease control, with no signs of further recurrence at 4 years' follow-up.

Cowden syndrome: report of two cases and review of clinical presentation and management of a rare colorectal polyposis.

BACKGROUND/AIMS: Cowden syndrome (CS) is a rare and complex disease inherited through an autosomal dominant trait associated with germline mutations of the PTEN gene. OBJECTIVE: This article reports 2 female patients with classic features of the syndrome and reviews the current guidelines regarding diagnosis and surveillance. REVIEW: Although it exhibits variable clinical expressivity, the diagnosis is based on characteristic mucocutaneous alterations such as multiple facial trichilemmomas, oral mucosal papillomatosis, and acral and palmoplantar keratoses. These manifestations often precede systemic involvement. Extracutaneous lesions include fibrocystic disease of the breast, thyroid goiters or adenomas, multiple polyposis of the gastrointestinal tract, and ovarian cysts. Gastrointestinal polyps are usually asymptomatic, and the risk of gastrointestinal cancer is not greatly increased. Otherwise, an important feature of Cowden's disease is the greater risk of breast and thyroid cancer. CONCLUSIONS: Because of the potentially serious associations with internal malignancy, early and accurate diagnosis of CS is essential. For this reason, all patients must be screened for occult malignancies and undergo close surveillance throughout lifetime.

Adenocarcinoma after ileoanal anastomosis for familial adenomatous polyposis: review of risk factors and current surveillance apropos of a case.

Restorative proctocolectomy has become the most common surgical option for familial adenomatous polyposis (FAP) patients, based on the premise that it provides good functional results and reduces colorectal cancer risk. But several adenomas may develop in the pouch mucosa over the years, and even cancer at the anastomosis or in the pouch mucosa has been reported rarely. This article aims to describe a case of pouch cancer after restorative proctocolectomy for FAP, reviewing the possible causes of this unfortunate outcome. A 40-year-old man started presenting with fecal blood loss 12 years after restorative proctocolectomy with mucosectomy and hand-sewn anastomosis for FAP. Proctologic examination revealed an elevated mass 3 cm from the anal margin, which biopsy determined to be a mucinous adenocarcinoma. The patient underwent pouch excision and terminal ileostomy. Histologic analysis showed a 2.2 cm mucinous adenocarcinoma between the ileal and anal mucosa (T2N0Mx) and multiple tubular microadenomas in the ileal pouch. The present case and the data presented here suggest that restorative proctocolectomy is not a "cancer-free" alternative to ileorectal anastomosis, because it does not remove the risk of metachronous intestinal neoplasia. Although the long-term risk of malignancy is not known, lifelong follow-up seems to be necessary after restorative proctocolectomy. Current recommendations for pouch surveillance are presented.

Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy.

OBJECTIVE: The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection. PATIENTS AND METHODS: All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-microm paraffin sections were obtained from each lymph node, cut at 50 microm apart from each other. The results were reviewed by two independent pathologists. RESULTS: Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months. CONCLUSION: Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.

Preoperative chemoradiation therapy for low rectal cancer. Impact on downstaging and sphincter-saving operations.

BACKGROUND/AIMS: Multimodality treatment is the preferred strategy in the management of low rectal adenocarcinoma. Preoperative chemoradiation therapy (CRT) associated with radical surgery may result in significant tumor downstaging, local control of the disease and high rates of sphincter-saving operations. METHODOLOGY: One hundred consecutive patients with advanced and resectable distal rectal cancer treated either by surgery alone or by preoperative chemoradiation followed by surgery were reviewed. Both groups were similar in tumor and patients characteristics. Treatment strategy was randomly selected. RESULTS: Mean tumor size in Group 1 (surgery alone) was 6.1 cm and 3.3 cm in Group 2 (CRT). In Group 1 (surgery alone), nine patients had stage I (18%), 20 had stage II (40%) and 21 had stage III disease (42%). In Group 2 (CRT), 6 patients had stage 0 (12%), 21 had stage I (42%), 12 had stage II (24%) and 11 had stage III disease (22%). Furthermore, for each T (except for T0-1) the presence of lymph node (LN) metastasis was significantly more frequent in Group 1. In Group 2 (CRT), there was a mean reduction of 27% of the initial tumor size. This reduction was observed in 58% of patients in this group (CRT). Finally, sphincter-saving operations were more frequently performed in Group 2 (CRT) even though tumor differentiation and distance from the anal verge were similar in both groups. CONCLUSIONS: Preoperative CRT followed by radical surgery is an effective treatment strategy for distal rectal cancer resulting in significant tumor size reduction and downstaging. Consequently, these effects may be responsible for higher rates of sphincter-saving operations performed in this subset of patients.

Correlaçäo das proteínas p53 e KI-67 com o prognóstico de pacientes com adenocarcinoma de reto distal / Correlation between p53 and KI-67 proteins and the follow-up of patients with rectum adenocarcinoma

Introduçäo: a capacidade de predizer o comportamento biológico e a resposta terapêutica seria de grande valia no tratamento do câncer de reto distal. Correlacionou-se a hiperexpressäo do p53 e Ki-67 com: parâmetros clinicopatológicos, resposta ao tratamento e prognóstico. Métodos: cortes histológicos de 72 pacientes com adenocarcinoma de reto distal foram corados para as proteínas p53 e Ki-67. Todos os pacientes receberam radioterapia (5.040cGy) e quimioterapia (5-fluorouracil+leucovorin). Os pacientes com resposta completa foram acompanhados sem tratamento cirúrgico, enquanto a ressecçäo foi realizada naqueles com resposta parcial. Resultados: hiperexpressäo do p53 foi detectada em 41/72 (56,9 por cento) tumores e alto índice de proliferaçäo (Ki-67) foi observado em 36/72 (50 por cento) tumores. Amostras teciduais coletadas pré e pós quimio/radioterapia apresentaram fidelidade no estado do p53 em todos os casos. Reatividade ao p53 e Ki-67 correlacionaram-se com recidiva da doença (p=0,02, p=0,006, respectivamente), contudo näo se associou com: idade, sexo, estádio T. N. M. e doença residual após quimio/radioterapia. Expressäo do p53 e Ki-67 associou-se com menor índice de sobrevivência geral (68,2 vs. 87,2 meses, p=0,005 e 59,9 vs. 89,3 meses, p=0,001, respectivamente) e intervalo livre de doença (59,4 vs. 81,7 meses, p=0,004 e 48,9 vs. 86,1 meses, p=0,0009, respectivamente). Conclusäo: as proteínas p53 e Ki-67 podem ser úteis na avaliaçäo prognóstica de pacientes com câncer de reto distal submetidos à terapia multimodal