Fábio Guilherme Campos

Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy Long-term Results

Objective:Report overall long-term results of stage 0 rectal cancer following neoadjuvant chemoradiation and compare long-term results between operative and nonoperative treatment. Methods:Two-hundred sixty-five patients with distal rectal adenocarcinoma considered resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU, Leucovorin and 5040 cGy. Patients with incomplete clinical response were referred to radical surgical resection. Patients with incomplete clinical response treated by surgery resulting in stage p0 were compared to patients with complete clinical response treated by nonoperative treatment. Statistical analysis was performed using χ2, Student t test and Kaplan-Meier curves. Results:Overall and disease-free 10-year survival rates were 97.7% and 84%. In 71 patients (26.8%) complete clinical response was observed following CRT (Observation group). Twenty-two patients (8.3%) showed incomplete clinical response and pT0N0M0 resected specimens (Resection group). There were no differences between patients demographics and tumors characteristics between groups. In the Resection group, 9 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 57.3 months in Observation Group and 48 months in Resection Group. There were 3 systemic recurrences in each group and 2 endorectal recurrences in Observation Group. Two patients in the Resection group died of the disease. Five-year overall and disease-free survival rates were 88% and 83%, respectively, in Resection Group and 100% and 92% in Observation Group. Conclusions:Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy. Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.

Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy.

Neoadjuvant chemoradiation therapy (CRT) is the preferred treatment option for distal rectal cancer. Complete pathological response after CRT has led to the proposal of nonoperative approach as an alternative treatment for highly selected patients with complete clinical response. However, patterns of failure following this strategy remains undetermined. Three hundred sixty-one patients with distal rectal cancer were managed by neoadjuvant CRT including 5-FU, leucovorin, and 5040 cGy. Tumor response assessment was performed at 8 weeks following CRT. Patients with complete clinical response were not immediately operated on and were closely followed. One hundred twenty-two patients were considered to have complete clinical response after the first tumor response assessment. Of these, only 99 patients sustained complete clinical response for at least 12 months and were considered stage c0 (27.4%) and managed nonoperatively. Mean follow-up was 59.9 months. There were 13 (13.1%) recurrences: 5 (5%) endorectal, 7 (7.1%) systemic, and 1 (1%) combined recurrence. All 5 isolated endorectal recurrences were salvaged. Mean recurrence interval was 52 months for local failure and 29.5 months for systemic failure. There were five cancer-related deaths after systemic recurrences. Overall and disease-free 5-year survivals were 93% and 85%. Even though surgery remains the standard treatment for rectal cancer, nonoperative treatment after complete clinical response following neoadjuvant CRT may be safe and associated with good survival rates in a highly selected group of patients. Survival in these patients is significantly affected by systemic failure. Exclusive local failure occurs late after CRT completion and is frequently amenable to salvage therapy.

Low rectal cancer

INTRODUCTION: The aim of this study was to evaluate the impact of combined radiotherapy and chemotherapy (leucovorin and 5-fluorouracil) on the treatment of potentially resectable low rectal cancer using the following end points: 1) toxicity of this combined modality regimen; 2) clinical and pathologic response rate and local control; 3) downstaging of the tumor and its influence on the number of sphincter-saving operations; 4) disease-free interval, patterns of relapse, and overall survival. METHODS: From 1991 to 1996, 118 patients with potentially resectable cases of histologically proven adenocarcinoma and no distant metastases were enrolled into this protocol. All patients were evaluated by clinical and proctologic examination, abdominal computed tomography, transrectal ultrasound, and chest radiography. Therapy consisted of 5,040 cGy (6 weeks) and concurrent leucovorin (20/mg/m2/day) with bolus doses of 5-fluorouracil administered intravenously at 425 mg/m2/day for three consecutive days on the first and last three days of radiation therapy. After two months, all patients underwent repeat evaluation and biopsy of any suspected residual lesions or scar tissue. RESULTS: Median follow-up was 36 months. Toxicity of chemotherapy regimen was minimum. Thirty-six patients (30.5 percent) were classified as being complete responders. In six of these patients, complete response was confirmed by the absence of tumor in the surgical specimens (3 abdominoperineal resections and 3 proctosigmoidectomies with coloanal anastomosis). In the remaining 30 patients, confirmation of a complete response was made by the absence of symptoms, negative findings on physical examination, and biopsy, transrectal ultrasound, and pelvic computed tomographic test results during follow-up. Eighty-two patients (69.4 percent) were considered incomplete responders. Residual lesions had already been identified during the first examination in 74 patients. In the other eight patients, residual tumor was only identified after 3 to 14 months. All patients underwent surgical treatment, except one patient who refused surgery. Eighty-seven patients underwent 90 surgical procedures: local excision, 9; coloanal anastomosis, 36; abdominoperineal resection, 4; Hartmanns procedure, 1. Isolated local recurrences occurred in five patients (4.3 percent) and combined local and distant failure in eight patients (6.7 percent). Ninety patients are alive and disease-free at a median follow-up of 36 months. CONCLUSIONS: Combined up-front chemoradiotherapy was associated with tolerable and acceptable side effects. A significant number of patients had complete disappearance of their tumors (30.5 percent) within a median follow-up of 36 months. This regimen spared 26.2 percent of patients from surgical treatment and allowed sphincter-saving management in 38.1 percent of patients who may have required abdominoperineal resection. Preliminary results of this trial suggests a reduction in the number of local recurrences and reinforces the concept that infiltrative low rectal cancer may be initially treated by chemoradiotherapy.

Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival

Neoadjuvant chemoradiation treatment (CRT) has resulted in significant tumor downstaging and improved local disease control for distal rectal cancer. The purpose of the present study was to determine the correlation between final stage and survival in these patients regardless of initial disease stage. Two hundred sixty patients with distal (0-7 cm from anal verge) rectal adenocarcinoma considered resectable were treated by neoadjuvant CRT with 5-FU and leucovorin plus 5040 cGy. Patients with incomplete clinical response 8 weeks after CRT completion were treated by radical surgical resection. Patients with complete clinical response were managed by observation alone. Overall survival and diseasefree survival were compared according to Kaplan-Meier curves and log-rank tests according to final stage. Seventy-one patients (28%) showed complete clinical response (clinical stage 0). One hundred sixtynine patients showed incomplete clinical response and were treated with surgery. In 22 of these patients (9%), pathologic examination revealed pT0 N0 M0 (stage p0), 59 patients (22%) had stage I, 68 patients (26%) had stage II, and 40 patients (15%) had stage III disease. Overall survival rates were significantly higher in stage c0 (P = 0.01) compared with stage p0. Disease-free survival rate showed better results in stage c0, but the results were not significant. Five-year overall and disease-free survival rates were 97.7% and 84% (stage 0); 94% and 74% (stage I); 83% and 50% (stage II); and 56% and 28% (stage III), respectively. Cancer-related overall and disease-free survival may be correlated to final pathologic staging following neoadjuvant CRT for distal rectal cancer. Also, stage 0 is significantly associated with improved outcome.

Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation Long-Term Results of a Prospective Trial (National Clinical Trial 00254683)

Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies.

The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer.

PURPOSE: Carcinoembriogenic antigen (CEA) is the most frequently used tumor marker in rectal cancer. A decrease in carcinoembriogenic antigen after radical surgery is associated with survival in these patients. Neoadjuvant chemoradiotherapy may lead to significant primary tumor downstaging, including complete tumor regression in selected patients. Therefore, we hypothesized that a decrease in CEA after neoadjuvant chemoradiotherapy could reflect tumor response to chemoradiotherapy, affecting final disease stage and ultimately survival. METHODS: Patients with distal rectal cancer managed by neoadjuvant chemoradiotherapy and available pretreatment and postchemoradiotherapy levels of CEA were eligible for the study. Outcomes studied included final disease stage, relapse, and survival, and these were compared according to initial CEA level, post-chemoradiotherapy CEA level, and the reduction in CEA. RESULTS: Overall 170 patients were included. Post-chemoradiotherapy CEA levels <5 ng/ml were associated with increased rates of complete clinical response and pathologic response. Additionally, postchemoradiotherapy CEA levels <5 ng/ml were associated with increased overall and disease-free survival (P = 0.01 and P = 0.03). There was no correlation between initial CEA level or reduction in CEA and complete response or survival. CONCLUSION: A postchemoradiotherapy CEA level <5 ng/ml is a favorable prognostic factor for rectal cancer and is associated with increased rates of earlier disease staging and complete tumor regression. Postchemoradiotherapy CEA levels may be useful in decision making for patients who may be candidates for alterative treatment strategies.

Inflammatory bowel diseases: principles of nutritional therapy

Inflammatory Bowel Diseases - ulcerative colitis and Crohns disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohns disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.

Manifestações extracolônicas da polipose adenomatosa familiar: incidência e impacto na evolução da doença

RACIONAL: A polipose adenomatosa familiar e doenca hereditaria de carater autossomico dominante, que frequentemente se associa a numerosas manifestacoes extracolonicas. OBJETIVOS: Relatar a incidencia de manifestacoes extracolonicas em nosso meio e analisar seu impacto na evolucao da doenca. PACIENTES E METODOS: Revisao dos prontuarios de pacientes com polipose adenomatosa familiar tratados no periodo de 1977 a 2001, relatando as manifestacoes extracolonicas associadas e suas complicacoes. RESULTADOS: Dos 59 pacientes com polipose adenomatosa familiar, 23 (38,9%) apresentaram alguma manifestacao extracolonica por ocasiao do diagnostico ou no seguimento. Foram registradas 37 diferentes manifestacoes (1,6 por paciente). As mais comuns foram osteomas e alteracoes na pigmentacao da retina, diagnosticadas em 25% e 20% dos pacientes pesquisados, respectivamente. Outras manifestacoes extracolonicas achadas foram adenomas do trato digestivo superior, cistos epidermoides, tumores desmoides (sete cada), câncer gastrico (tres) e câncer de tireoide (dois). Complicacoes importantes diretamente relacionadas aos tumores desmoides foram reportadas em seis pacientes, sendo obstrucao intestinal em quatro e hidronefrose em dois. Registraram-se obitos em dois pacientes (28,5%). CONCLUSOES: A incidencia de manifestacoes extracolonicas e alta (40%), podendo afetar a evolucao da doenca e a qualidade de vida dos pacientes. Por esses motivos, torna-se de fundamental importância a pesquisa, a prevencao e o tratamento adequado dessas manifestacoes na polipose adenomatosa familiar.

Preliminary results from digestive adaptation: a new surgical proposal for treating obesity, based on physiology and evolution

CONTEXT AND OBJECTIVE Most bariatric surgical techniques include essentially non-physiological features like narrowing anastomoses or bands, or digestive segment exclusion, especially the duodenum. This potentially causes symptoms or complications. The aim here was to report on the preliminary results from a new surgical technique for treating morbid obesity that takes a physiological and evolutionary approach. DESIGN AND SETTING Case series description, in Hospital Israelita Albert Einstein and Hospital da Polícia Militar, São Paulo, and Hospital Vicentino, Ponta Grossa, Paraná. METHODS The technique included vertical (sleeve) gastrectomy, omentectomy and enterectomy that retained three meters of small bowel (initial jejunum and most of the ileum), i.e. the lower limit for normal adults. The operations on 100 patients are described. RESULTS The mean follow-up was nine months (range: one to 29 months). The mean reductions in body mass index were 4.3, 6.1, 8.1, 10.1 and 10.7 kg/m2, respectively at 1, 2, 4, 6 and 12 months. All patients reported early satiety. There was major improvement in comorbidities, especially diabetes. Operative complications occurred in 7% of patients, all of them resolved without sequelae. There was no mortality. CONCLUSIONS This procedure creates a proportionally reduced gastrointestinal tract, leaving its basic functions unharmed and producing adaptation of the gastric chamber size to hypercaloric diet. It removes the sources of ghrelin, plasminogen activator inhibitor-1 (PAI-1) and resistin production and leads more nutrients to the distal bowel, with desirable metabolic consequences. Patients do not need nutritional support or drug medication. The procedure is straightforward and safe.

Regeneração hepática: papel dos fatores de crescimento e nutrientes

A regeneração hepática, representa um mecanismo de proteção orgânica contra a perda de tecido hepático funcionante seja por injúria química, viral, perda traumática, ou por hepatectomia parcial (HP)1-8. Na Grécia antiga, relatou-se a regeneração hepática através do mito de Prometheus. Tendo descoberto o segredo do fogo dos Deuses do Olimpo, Prometheus foi condenado a alimentar diariamente uma águia com uma porção do seu fígado. No entanto, durante a noite, seu fígado regenerava provindo a águia com eterno alimento e submetendo Prometheus a uma eterna tortura9-11. O primeiro modelo experimental bem sucedido para o estudo da regeneração hepática foi introduzido por Higgins e Anderson em 1931. Esse modelo contemplou a remoção cirúrgica dos lóbulos lateral esquerdo e mediano do fígado de ratos, constituindo aproximadamente 67 a 70% da massa hepática total desses animais12,-17,4,7,8. Apesar de ser largamente utilizado, o termo “regeneração” é biologicamente incorreto, uma vez que a resposta induzida pelo dano tecidual hepático promove hiperplasia e hipertrofia compensatória do tecido remanescente, até o restabelecimento da massa hepática primitiva. No entanto, os lóbos ressecados não são recuperados18,19,4,6,7,10. Nos últimos anos surgiram novos conhecimentos sobre os fatores envolvidos no processo de regeneração hepática, assim como o efeito específico de fatores de crescimento e nutrientes. Portanto, o objetivo desta revisão foi atualizar estes conhecimentos, dando ênfase ao seu aspecto metabólico nutricional. REGENERAÇÃO HEPÁTICA