Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision.

Nipple discharge (ND) is a common symptom seen in breast cancer clinics. The primary aim of this study was to identify preoperative risk factors for breast cancer in patients with pathologic ND. The secondary aim was to assess the clinical and pathological effectiveness of physical examination, galactography, cytological examination of the discharge, selective duct excision and ductoscopy. All patients operated on between 1975 and 2008 who presented with ND as their only symptom was analyzed. Discharge's characteristics, cytological data and galactography reports were recorded. The relationship between each individual finding and the risk of breast cancer was calculated. For each diagnostic tool, the sensitivity, specificity and complication rates were calculated and compared. Nine-hundred-fifteen patients underwent selective duct excision. Two-hundred-nineteen patients (23.9%) were found to be affected by carcinoma. In 100/330 (30.3%) patients with bloody discharge and in 42/239 (17.6%) patients with serous secretion cancer was detected (P = 0.004, P = 0.013, respectively). Patients with sero-sanguinous or coloured discharge had the same risk of cancer as the population analyzed (23.9%, P = NS). Galactographic finding of irregular stenosis seemed to be associated with a higher risk of cancer (P = 0.0001). Cytological findings C5 and C4 were associated with cancer (P = 0.001). Selective duct excision showed highest sensitivity and specificity. In conclusion, the well established role of bloody secretion is confirmed. The supposed benign aetiology of serous, coloured or sero-sanguinous discharge is questionable. The high specificity of the cytological exam justifies routine examination of the ND. Selective duct excision can be considered as the diagnostic gold-standard.

A preliminary audit experience of surgery for rectal cancer after neoadjuvant chemoradiation therapy.

AIMS AND BACKGROUND: A surgical audit is a systematic critical analysis of surgical performance, with the goal to improve the quality of patient care. Rectal cancer surgery is one of the most delicate procedures in the field of surgical oncology, with significant variations in terms of complications from center to center. Neoadjuvant chemoradiation therapy leads to a significant reduction in local recurrences in patients with locally advanced lower and medium rectal cancer. The aim of the study was to evaluate the influence of neoadjuvant chemoradiation therapy on postoperative morbidity and mortality in patients with rectal cancer. METHODS AND STUDY DESIGN: From January 1, 2003, to December 31, 2007, patients who underwent elective surgical resection for lower and medium rectal cancer in our Surgical Unit were prospectively analyzed. Patients (n=42) were divided into two groups: (1) those treated with neoadjuvant chemotherapy and consequent surgical resection (19/42); (2) those treated with primary surgical treatment (23/42). P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity) and CR-POSSUM (ColoRectal-POSSUM) scores were calculated for each patient group. Thirty-day mortality and morbidity rates were prospectively collected in a comprehensive data base. Data were evaluated by comparing the predictions of the two scoring systems in both study groups with clinically observed mortality and morbidity rates. RESULTS: In group 1, no death was registered (0/19). The P-POSSUM and CR-POSSUM expected mortality was 2.43% and 4.52%, respectively (P > 0.05). In group 2, a single death was documented (1/23, 4.35%). The P-POSSUM and CR-POSSUM expected mortality was 2.1% and 4.94%, respectively. The postoperative complications rate for group 1 was 10.52% (2/19) compared to 34.88% as expected from the P-POSSUM score (P < 0.05). In group 2, a postoperative complication rate of 39.13% (9/23) was observed compared to 34.26% as expected from the P-POSSUM score (P > 0.05). CONCLUSIONS: No significant influence on morbidity or mortality was detected in patients who underwent neoadjuvant radio-chemotherapy.

The challenge of education in colorectal cancer surgery: a comparison of early oncological results, morbidity, and mortality between residents and attending surgeons performing an open right colectomy.

OBJECTIVES: Ongoing education in surgical oncology is mandatory in a modern residency program. Achieving acceptable morbidity and mortality rates, together with oncological adequacy, is mandatory. The aim of the study was to compare early surgical outcomes in 2 groups of patients, those operated on by a surgical resident supervised by an attending surgeon and those operated on by 2 attending surgeons. DESIGN: Data from consecutive patients with right colon cancer undergoing a right hemicolectomy were collected and analyzed. The patients were divided into 2 groups according to the surgeons' credentials: residents supervised by an attending surgeon and 2 attending surgeons. To evaluate the specific case mix of the 2 groups, the Portsmouth-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (P-POSSUM) was calculated. Observed over expected 30-day morbidity and mortality rates were compared for the 2 groups. The number of lymph nodes retrieved was chosen to determine oncological appropriateness. Duration of the procedures was also recorded. RESULTS: From January 2008 to January 2012, 139 patients underwent an right hemicolectomy (76 resections performed by surgical residents and 63 by attending surgeons). Patient characteristics according to the P-POSSUM score and cancer stage were equivalent in the 2 groups. Observed over expected mortality and morbidity rates according to P-POSSUM were 0%/3.5% and 21.6%/40.5%, respectively, for the resident group (p = nonsignificant, p = 0.01) and 4.7%/5.8% and 25.4%/42.9%, respectively, for the attending surgeons (p = nonsignificant). The node count was 23.6 nodes for residents and 23.1 for the attending surgeons. The length of surgery was 159.9 minutes vs 159.4 minutes for residents and attending surgeons, respectively. CONCLUSIONS: Surgical oncology training of residents by expert surgeons cannot put patient's safety at risk. Our study showed that oncological accuracy and the 30-day complication rate were equivalent to the standard of care in both groups. Duration of the procedure was not affected by the presence of a trainee.

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes.

Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain 15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.

The EGFR R521K polymorphism influences the risk to develop colorectal cancer.

Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.

Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The present work aimed at identifying a set of specific mRNAs expressed in colon tissue but not in blood cells. These mRNAs may represent useful markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay, following RNA extraction from peripheral blood samples. Using a data-mining tool called cDNA digital gene expression displayer (DGED), based on serial analysis of gene expression (SAGE) from the Cancer Genome Anatomy Project (CGAP) database, 4-colon and 14-blood cDNA libraries were analyzed. We selected 7 genes expressed in colon tissue but not in blood and were able to test 6 of them by RT-PCR in peripheral blood of CRC patients and healthy controls. We present a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as candidate markers of malignancy in blood samples of patients with colon cancer. SAGE DGED provided a list of the best candidate mRNAs predicted to detect colon cells in the blood, namely those encoding the following proteins: hypothetical protein LOC644844 (LOC644844, whose cDNA was not amplifiable), fatty acid binding protein 1 (FABP1), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), mucin 13 cell surface associated (MUC13), guanylate cyclase activator 2A (GUCA2A), amiloride binding protein 1 (ABP1), galactoside-binding, solute carrier family 26, member 3 (SLC26A3). The mRNA expression of these genes was evaluated in 8 samples from subjects diagnosed with CRC and 9 from healthy controls. We observed the expression of 2 of the 6 investigated genes in the blood samples of the vast majority of patients considered, but also in a subset of the controls. Our data confirm the extreme sensitivity of RT-PCR, making this technique able to detect minimal amounts of mRNA expressed in a non-tissue-specific manner. Moreover, DGED remains a powerful tool to identify candidate epithelial markers in blood, such as colon related mRNAs. However, to date, none of these qualified as tumour markers.

Diffuse cavernous haemangioma of the rectum and anus: an unusual case of rectal bleeding with challenging management.

Diffuse cavernous haemangioma of the rectum (DCHR) is an uncommon vascular pathology usually diagnosed in younger patients (5-25 years old) with painless, recurrent rectal bleeding. Here, an unusual case of an older patient with sigmoid adenocarcinoma and concomitant diffuse DCHR from the rectum to the distal edge of the anal canal is reported.The purpose of this article is to report this unusual case and to discuss pitfalls in diagnosis, preoperative assessment and treatment of DCHR.

An easy-to-use solution for clinical audit in colorectal cancer surgery.

BACKGROUND: Clinical audit has been increasingly required for the accreditation process in every modern healthcare system. Data collection and analysis are excessively time-consuming in everyday practice. The primary aim of our study was to evaluate the effectiveness of an innovative database to assist surgeons in monitoring clinical practice outcomes in colorectal cancer surgery. The second purpose was to compare observed mortality rates to 3 risk-predicting operative scoring systems. METHODS: Data were evaluated from 208 consecutive patients undergoing elective and emergency surgery for colorectal cancer over a 2-year period (2003-2004). A new database was developed with specific queries to compare the observed and the expected mortality rates according to 3 scoring systems: the Portsmouth-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (P-POSSUM), the ColoRectal-Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (CR-POSSUM), and the Association of ColoProctology or Great Britain & Ireland (ACPGBI) score. Results were discussed at regular intervals. Surgeons' satisfaction with each system was evaluated with a questionnaire. RESULTS: The observed mortality rate was 6.25%, which was significantly lower than the values predicted by CR-POSSUM and ACPGBI colorectal scores (9.14% and 19.42%, respectively; P < .05). P-POSSUM was the most accurate predictor of mortality, with a value of 7.93%. A total of 80% of the surgical staff considered this type of surgical audit activity as clinically useful. CONCLUSION: The study confirms the usefulness of a dedicated database in a surgical audit activity. The ACPGBI colorectal score largely overestimated 30-day mortality in our experience.