Davide Zattoni

Personalized surgical management of colorectal cancer in elderly population

Colorectal cancer (CRC) in the elderly is extremely common but only a few clinicians are familiar with the complexity of issues which present in the geriatric population. In this phase of the life cycle, treatment is frequently suboptimal. Despite the fact that, nowadays, older people tend to be healthier than in previous generations, surgical undertreatment is frequently encountered. On the other hand, surgical overtreatment in the vulnerable or frail patient can lead to unacceptable postoperative outcomes with high mortality or persistent disability. Unfortunately, due to the geriatric patient being traditionally excluded from randomized controlled trials for a variety of factors (heterogeneity, frailty, etc.), there is a dearth of evidence-based clinical guidelines for the management of these patients. The objective of this review was to summarize the most relevant clinical studies available in order to assist clinicians in the management of CRC in the elderly. More than in any other patient group, both surgical and non-surgical management strategies should be carefully individualized in the elderly population affected by CRC. Although cure and sphincter preservation are the primary goals, many other variables need to be taken into account, such as maintenance of cognitive status, independence, life expectancy and quality of life.

A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk.

The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case-control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.

Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection

Colorectal cancer (CRC) is the third most common cancer in the world. A significant survival rate is achieved if it is detected at an early stage. A whole blood screening test, without any attempt to isolate blood fractions, could be an important tool to improve early detection of colorectal cancer. We searched for candidate markers with a novel approach based on the Transcriptome Mapper (TRAM), aimed at identifying specific RNAs with the highest differential expression ratio between colorectal cancer tissue and normal blood samples. This tool permits a large-scale systematic meta-analysis of all available data obtained by microarray experiments. The targeting of RNA took into consideration that tumour phenotypic variation is associated with changes in the mRNA levels of genes regulating or affecting this variation. A real time quantitative reverse transcription polymerase chain reaction (qRT- PCR) was applied to the validation of candidate markers in the blood of 67 patients and 67 healthy controls. The expression of genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 resulted as being statistically different. In particular ROC curves attested for TSPAN8 an AUC of 0.751 with a sensitivity of 83.6% and a specificity of 58.2% at a cut off of 10.85, while the panel of the two best genes showed an AUC of 0.861 and a sensitivity of 92.5% with a specificity of 67.2%. Our preliminary study on a total of 134 subjects showed promising results for a blood screening test to be validated in a larger cohort with the staging stratification and in patients with other gastrointestinal diseases.

How to select elderly colorectal cancer patients for surgery: a pilot study in an Italian academic medical center.

Objective Cancer is one of the most common diagnoses in elderly patients. Of all types of abdominal cancer, colorectal cancer (CRC) is undoubtedly the most frequent. Median age at diagnosis is approximately 70 years old worldwide. Due to the multiple comorbidities affecting elderly people, frailty evaluation is very important in order to avoid over- or under-treatment. This pilot study was designed to investigate the variables capable of predicting the long-term risk of mortality and living situation after surgery for CRC. Methods Patients with 70 years old and older undergoing elective surgery for CRC were prospectively enrolled in the study. The patients were preoperatively screened using 11 internationally-validated-frailty-assessment tests. The endpoints of the study were long-term mortality and living situation. The data were analyzed using univariate Cox proportional-hazard regression analysis to verify the predictive value of score indices in order to identify possible risk factors. Results Forty-six patients were studied. The median follow-up time after surgery was 4.6 years (range, 2.9-5.7 years) and no patients were lost to follow-up. The overall mortality rate was 39%. Four of the patients who survived (4/28, 14%) lost their functional autonomy. The preoperative impaired Timed Up and Go (TUG), Eastern Cooperative Group Performance Status (ECOG PS), Instrumental Activities of Daily Living (IADLs), Vulnerable Elders Survey (VES-13) scoring systems were significantly associated with increased long term mortality risk. Conclusion Simplified frailty-assessing tools should be routinely used in elderly cancer patients before treatment in order to stratify patient risk. The TUG, ECOG-PS, IADLs and VES-13 scoring systems are potentially able to predict long-term mortality and disability. Additional studies will be needed to confirm the preliminary data in order to improve management strategies for oncogeriatric surgical patients.

The management of bilateral myelolipoma: Case report and review of the literature

Highlights • The adrenal myelolipoma is a rare benign tumor of the adrenal gland.• In some cases, they can be found bilaterally.• Symptomatic tumors or those bigger than 7 cm are usually treated surgically.• Small adrenal myelolipomas (< 7 cm) and asymptomatic ones can be managed conservatively.• These neoplasms are benign and at low risk of rupture and whenever possible the endocrine function must be preserved.

Has breast cancer in the elderly remained the same over recent decades? A comparison of two groups of patients 70 years or older treated for breast cancer twenty years apart

OBJECTIVES Breast cancer (BC) in the elderly population is by far the most frequent malignancy in Western countries; however, little evidence is available regarding the specific management of this group. The purpose of this study was to identify how the biological and clinical characteristics of cancer have changed over the past 20years by comparing two groups of elderly patients with breast cancer operated on 20years apart. The secondary endpoint was to underline potential changes in surgical strategy over the past 20years. MATERIALS AND METHODS One group of consecutive elderly patients undergoing surgery for BC between January 1990 and December 1993 (Group A), and one group undergoing surgery between January 2008 and December 2011 (Group B) were identified and analyzed. Data regarding surgical treatment, stage, tumor grading, hormonal and HER2/neu receptors, and Ki-67 were collected and compared. RESULTS A total of 422 elderly patients underwent surgical treatment, 142 in Group A and 280 in Group B. An earlier stage at presentation was detected in Group B, T1 (57.5% B vs. 31.6% A) and N0 (64.6% B vs. 54.2% A). Surgical treatment in the first group was more extensive while conservative procedures were more frequently performed in the second group. Despite the earlier presentation, tumor grade was higher in Group B (G3 10.6% A vs. 32.1% B, p<0.05). Overexpression of Ki-67 was again more frequent in Group B (56.2% B vs. 32.5% A, p<0.05). Hormonal and HER2/neu receptor expression was comparable. CONCLUSIONS Nowadays, elderly patients with BC are more likely to present at an early stage; therefore, conservative surgery is a feasible option. Despite potential bias related to changes of pathology and immunohistochemistry examination techniques over the decades, the biological characteristics of recent patients with BC seem to be consistent with more aggressive tumors. Tailored treatment should be offered with regard to biological age, the cancer-specific profile and active life expectancy.

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.

A Simple Screening Tool to Predict Outcomes in Older Adults Undergoing Emergency General Surgery: The frailty assessment in emergency surgery

To determine whether the Flemish version of the Triage Risk Screening Tool (fTRST) can be used to accurately assess frailty in an emergency setting.

The R521K polymorphism of EGFR influences the risk of colorectal cancer

In colorectal cancer (CRC) epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been found frequently over-expressed. New therapies directed against EGFR have been developed in many human cancers. Unexpectedly, EGFR alterations could be good prognostic indicators, like in lung cancer, where an EGFR variant in non-smoker female patients is associated with higher survival after surgery and increases the efficiency of therapy based on EGFR inhibitors. The role of the genetic polymorphisms of the EGFR family members in colorectal cancer development has not been completely explored. In our preliminary study, three missense polymorphisms mapping in EGFR family members have been investigated in the peripheral blood of a small Italian sample size of 70 patients and 72 controls to verify if they could be considered CRC susceptibility factors. For the first time, the evidence of genotype association was found for the R521K EGFR polymorphism: the protective effect for this variant allele has been found to reduce the risk for colon cancer onset.

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.