Evolving treatment strategies for colorectal cancer: A critical review of current therapeutic options

Management of rectal cancer has markedly evolved over the last two decades.New technologies of staging have allowed a more precise definition of tumor extension.Refinements in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this malignancy.Although,preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors,many controversial matters in management of rectal cancer still need to be defined.These include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy,the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor resection.In this article,after an extensive search in PubMed and Embase databases,we critically review the current strategies and the most debatable matters in treatment of rectal cancer.

In vivo assessment of intratumoral aspirin injection to treat hepatic tumors

AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.

Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic

AIM:To determine the prevalence of a family history suggestive of Lynch syndrome (LS) among patients with colorectal cancer (CRC) followed in a coloproctology outpatient clinic in Southern Brazil.METHODS:A consecutive sample of patients with CRC were interviewed regarding personal and family histories of cancer.Clinical data and pathology features of the tumor were obtained from chart review.RESULTS:Of the 212 CRC patients recruited,61 (29%) reported a family history of CRC,45 (21.2%) were diagnosed under age 50 years and 11 (5.2%) had more than one primary CRC.Family histories consistent with Amsterdam and revised Bethesda criteria for LS were identified in 22 (10.4%) and 100 (47.2%) patients,respectively.Twenty percent of the colorectal tumors had features of the high microsatellite instability phenotype,which was associated with younger age at CRC diagnosis and with Bethesda criteria (P < 0.001).Only 5.3% of the patients above age 50 years had been previously submitted for CRC screening and only 4% of patients with suspected LS were referred for genetic risk assessment.CONCLUSION:A significant proportion of patients with CRC were at high risk for LS.Education and training of health care professionals are essential to ensure proper management.

Lack of correlation between p53 codon 72 polymorphism and anal cancer risk

AIM:To investigate the potential role of p53 codon 72 polymorphism as a risk factor for development of anal cancer. METHODS:Thirty-two patients with invasive anal carcinoma and 103 healthy blood donors were included in the study.p53 codon 72 polymorphism was analyzed in blood samples through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS:The relative frequency of each allele was 0.60 for Arg and 0.40 for Pro in patients with anal cancer, and 0.61 for Arg and 0.39 for Pro in normal controls. No significant differences in distribution of the codon 72 genotypes between patients and controls were found. CONCLUSION:These results do not support a role for the p53 codon 72 polymorphism in anal carcinogenesis.

Critical appraisal of laparoscopic lavage for Hinchey Ⅲ diverticulitis

Laparoscopic lavage and drainage is a novel approach for managing patients with Hinchey Ⅲ diverticulitis. However, this less invasive technique has important limitations, which are highlighted in this systematic review. We performed a Pub Med search and identified 6 individual series reporting the results of this procedure. An analysis was performed regarding treatment-related morbidity, success rates, and subsequent elective sigmoid resection. Data was available for 287 patients only, of which 213(74%) were actually presenting with Hinchey Ⅲ diverticulitis. Reported success rate in this group was 94%, with 3% mortality. Causes of failure were:(1) ongoing sepsis;(2) fecal fistula formation; and(3) perforated sigmoid cancer. Although few patients developed recurrent diverticulitis in follow-up, 106 patients(37%) eventually underwent elective sigmoid resection. Our data indicate that laparoscopic lavage and drainage may benefit a highly selected group of Hinchey Ⅲ patients. It is unclear whether laparoscopic lavage and drainage should be considered a curative procedure or just a damage control operation. Failure to identify patients with either:(1) feculent peritonitis(Hinchey Ⅳ);(2) persistent perforation; or(3) perforated sigmoid cancer, are causes of concern, and will limit the application of this technique.

Non-Hodgkin＇s Lymphoma： An Important Differential Diagnosis in Inflammatory Bowel Disease

To the Editor： The gastrointestinal tract （GIT） is the most common extranodal location ofnon-Hodgkin＇s lymphoma, but it represents only 0.4% of primary colonic malignancies. Symptoms are nonspecific and may include diarrhea, constipation, abdominal pain, weight loss, and gastrointestinal bleeding. In colon, the most common types are conventional large cell lymphoma, mucosa-associated lymphoid tissue lymphoma, and T-cell lymphoma.