Surgery has a key role for quality assurance of colorectal cancer screening programs: impact of the third level multidisciplinary team on lymph nodal staging.

PURPOSE: From 2011 to 2013 in the area of the Naples 3 public health district (ASL-NA3), a colorectal cancer screening program (CCSP) was developed. In order to stress the need of quality assurance procedures for surgery and pathology, a third level oncologic pathway was added and set up at a referral colorectal cancer center (RC). Lymph nodal (LN) harvesting, as a process indicator, and nodal positivity were adopted for an interim analysis. METHODS: The program was implemented by a series of audit meetings and a double type of multidisciplinary team (MDT): "horizontal" and "vertical." Three hundred and forty colorectal cancer (CRC) patients underwent surgery: 119 chose to be operated at the RC (Gr In), 65 were operated at 22 district hospitals (DH) (Gr Out), and 156 symptomatic not screened patients were operated at the RC (Gr Sym). RESULTS: Statistical analysis revealed differences between Gr In and Gr Out colon groups both for LN harvesting (median of 26 and 11, respectively, P = 0.0001), and for nodal positivity after the first screening round (34.78 and 19.45%, respectively, P = 0.0169). Results were all the more significant in a subset analysis on early T stage colon subgroups (In vs Out) both for LN harvesting (P < 0.0001) and nodal positivity (P < 0.0001). CONCLUSION: xSignificant differences between RC and DHs were found, particularly for early-stage CRC patients. LN harvesting should be considered as a surrogate marker of quality assurance for at least screening hospitals for "minimum best" standard of care. This should lead to set up a third level in any CCSP.

Effects of Curative Colorectal Cancer Surgery on Exhaled Volatile Organic Compounds and Potential Implications in Clinical Follow-up.

OBJECTIVE: The aim of this study was to determine whether the volatile organic compounds (VOCs) pattern in colorectal cancer (CRC) patients is modified by curative surgery for a potential application in the oncologic follow-up. BACKGROUND: CRC has been proved to induce metabolic derangements detectable by high through-output techniques in exhaled breath showing a specific pattern of VOCs. METHODS: Forty-eight CRC patients and 55 healthy controls (HC) entered the study. Thirty-two patients (M/F: 1.4; mean age 63 years) attended the oncologic follow-up (mean 24 months) and were found disease-free. Breath samples were collected under similar environmental conditions into a Tedlar bags and processed offline by thermal-desorption gas chromatography-mass spectrometry (TD-GC-MS). VOCs were selected by U test to build a Probabilistic Neural Network (PNN) model to set-up a training phase, which was cross-validated using the leave-one out method. RESULTS: A total of 11 VOCs were finally selected for their excellent discriminant performance in identifying disease-free patients in follow-up from CRC patients before surgery, (sensitivity 100%, specificity 97.92%, accuracy 98.75%, and AUC: 1). The same VOCs pattern discriminated follow-up patients from HC, with a sensitivity of 100%, specificity of 90.91%, accuracy of 94.25%, and AUC 0.959. CONCLUSIONS: Exhaled VOCs pattern from CRC patients is modified by cancer removal confirming the tight relationship between tumor metabolism and exhaled VOCs. PNN analysis provides a high discriminatory tool to identify patients disease-free after curative surgery suggesting potential implications in CRC screening and secondary prevention.

Prevalence of constipation in a tertiary referral Italian Colorectal Unit.

INTRODUCTION: Epidemiology data on constipation are not commonly available, particularly in Italy Here we review the prevalence and clinical features of constipated patients attending a tertiary referral Italian center. METHODS: Clinical data of patients attending our Coloproctology Unit in the last 15 years and complaining of constipation as the main clinical features were retrospectively analyzed. Rome-III criteria were adoptedto define constipation. RESULTS: 1041/11881 patients were affected by chronic constipation (8.8%), 376 had slow-transit constipation, 497 obstructed defecation and 168 both types of constipation. 76% of them were females. Patients distribution according to sex and age was Gaussian-like only in females. In the slow-transit group, constipation was idiopathic in 59.3% and secondary to other causes in 40.7% . In patients with anatomic obstructed defecation, rectocele and intussusceptions were the main findings, while pelvic floor dissynergia was the main finding in functional outlet obstruction, although more frequently all these components were associated. In 14.8% no apparent cause was identified. CONCLUSION: Constipation accounts for about 9% of patients attending a tertiary referral Colorectal Unit. Females were much more frequently affected in both types of constipation. Anatomic and functional defecatory disturbances are frequently associated, although in 15% no evident causes were identified. KEY WORDS: Constipation, Epidemiology, Obstructed defecation, Slow transit constipation.

MicroRNA in colorectal cancer: new perspectives for diagnosis, prognosis and treatment.

Colorectal cancer (CRC) is a common condition and represents a lethal disease, following a sequential progression from adenoma to carcinoma. Interfering with such natural history of CRC offers clues to prevention and cure, but current screening methods for CRC are still limited by unsatisfactory sensitivity and specificity. Novel diagnostic, prognostic tools are therefore being actively investigated for CRC. The discovery of microRNAs (miRNAs) has led to active research focusing on their role in cancer and several crucial pathways involving angiogenesis, cancer-stem-cell biology, epithelial-mesenchymal transition, formation of metastasis, and drug resistance. MiRNAs might soon represent novel prognostic and diagnostic tools in patients at high risk of CRC or being diagnosed with CRC. MiRNA might prove useful also as therapeutic tools, since dysregulation of miRNAs in cancer cells results in higher levels of messenger RNA (mRNA) specific to tumor promoter genes or tumor suppressor genes. Thus, novel anticancer therapies might originate from manipulation of oncogenic or tumor suppressor miRNAs in CRC. In this review, the innovative aspects of miRNA are discussed, with respect to biogenesis, their role in CRC, and their potential use as biomarkers. Before miRNAs can become available in the clinical setting, however, a number of large prospective studies are still required.

New strategies for colorectal cancer screening.

Colorectal cancer (CRC) is still one of the leading causes of cancer-related death in Western countries, despite major improvements in its treatment. The dramatically high social and economic impact of CRC on human health makes the identification of a reliable screening tool of paramount importance. Current screening methods, such as the fecal occult blood test and colonoscopy do not adequately meet the ideal requisites of a screening test because, even if they are effective, they are limited first by too low specificity and sensitivity, or second by high invasiveness, costs and risk. Nowadays extended efforts are made by researchers to look for more reliable and effective screening tests based on a systems biology approach, using biological samples easily available, such as urine, breath, serum and feces. The effectiveness and reliability of several new attempts to screen these patients by non-invasive analysis of their biological samples using genomic (genetic and epigenetic alteration), transcriptomic (miRNA), proteomic (cancer-related antigens, new antibodies against tumor-associated antigens, mutated proteins) and metabolomic (volatile organic metabolites) methods are discussed in this review. Among the most interesting new screening tools, fecal fluorescent long-DNA, fecal miRNA and metabolomic evaluation in breath and/or serum seem to be most promising.

Strangulated ileal trans-coloanal-anastomotic hernia: a complication of Altemeier's procedure previously never reported.

A postoperative complication after Altemeier operation, so far never reported, is described in a 42 years old mentally disabled patient with external full thickness rectal prolapse who usually had prolonged straining at defecation. After 6 d from perineal rectosigmoidectomy, the patient, was discharged free of complications. Four days later he was readmitted in emergency for strangulated perineal trans-anastomotic ileal hernia that occurred at home during efforts to defecate. The clinical feature required an emergency operation for repositioning the ileal loops into the abdomen, resection of the necrotic ileum, and end colostomy. The outcome of the second operation was free of complication and the patient was discharged on the 6(th) postoperative day. In conclusion, after Altemeier operation prolonged straining at defecation should be carefully avoided.

ERß expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis.

OBJECTIVES: The APC gene mutation triggers familial adenomatous polyposis (FAP) and approximately 80% of sporadic colorectal cancers. FAP summarizes the natural history of colorectal cancer because low- and high-grade dysplastic lesions and adenocarcinoma are simultaneously present in the same patients free from individual and environmental variability factors. Estrogen receptor beta (ERß) has recently been suggested as the most likely mediator of estrogen-related anti-carcinogenic effects in Apc(Min-/+) mice and humans. In this study we assessed the ERß expression in the intestinal mucosa of FAP patients to verify its possible involvement in tumor progression in colorectal cancer. MATERIAL AND METHODS: ERß and ERα expression, cell proliferation (Ki-67) and apoptosis (TUNEL), were evaluated on archival biopsy material from six patients with FAP who underwent colectomy. RESULTS: A progressive significant decrease of ERß expression was observed in the different stages of the disease as compared to normal mucosa (p < 0.001). Interestingly, a decreased ERß expression was directly correlated with apoptosis (r = 0.76, p < 0.001), and inversely correlated with cell proliferation (r = 0.54, p < 0.05). CONCLUSIONS: ERß expression is related to the severity of the disease, supporting the role of ERß as a relevant biomarker of tumor progression and possible chemopreventive target in patients at risk of colonic neoplasia.