Frailty assessment can predict textbook outcomes in senior adults after minimally invasive colorectal cancer surgery.

AIM: Colorectal cancer (CRC) surgery can be associated with suboptimal outcomes in older patients. The aim was to identify the correlation between frailty and surgical variables with the achievement of Textbook Outcome (TO), a composite measure of the ideal postoperative course, by older patients with CRC. METHOD: All consecutive patients ≥70years who underwent elective CRC-surgery between January 2017 and November 2021 were analyzed from a prospective database. To obtain a TO, all the following must be achieved: 90-day survival, Clavien-Dindo (CD) < 3, no reintervention, no readmission, no discharge to rehabilitation facility, no changes in the living situation and length of stay (LOS) ≤5days/≤14days for colon and rectal surgery respectively. Frailty and surgical variables were related to the achievement of TO. RESULTS: Four-hundred-twenty-one consecutive patients had surgery (97.7% minimally invasive), 24.9% for rectal cancer, median age 80 years (range 70-92), median LOS of 4 days (range 1-96). Overall, 288/421 patients (68.4%) achieved a TO. CD 3-4 complications rate was 6.4%, 90-day mortality rate was 2.9%. At univariate analysis, frailty and surgical variables (ileostomy creation, p = 0.045) were related to. However, multivariate analysis showed that only frailty measures such as flemish Triage Risk Screening Tool≥2 (OR 1.97, 95%CI: 1.23-3.16; p = 0.005); Charlson Index>6 (OR 1.61, 95%CI: 1.03-2.51; p = 0.036) or Timed-Up-and-Go>20 s (OR 2.06, 95%CI: 1.01-4.19; p = 0.048) independently predicted an increased risk of not achieving a TO. CONCLUSION: The association between frailty and comprehensive surgical outcomes offers objective data for guiding family counseling, managing expectations and discussing the possible loss of independence with patients and caregivers.

Prediction of functional loss in emergency surgery is possible with a simple frailty screening tool.

BACKGROUND: Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery. METHODS: All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss. RESULTS: Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71-28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2. CONCLUSION: fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting.

How best to palliate and treat emergency conditions in geriatric patients with colorectal cancer.

Almost one third of colorectal cancer (CRC) cases are diagnosed in an emergency setting, mostly among geriatric patients. Clinical scenarios are often complex and decision making delicate. Besides the obvious need to consider the patient's and/or family and care givers' desires, the surgeon should be able to make the best educated guess on future outcomes in three areas: oncological prognosis, morbidity and mortality risk, and long-term functional loss. Using simple and brief tools for frailty screening reasonable treatment goals with curative or palliative intent can be planned. The most frequent clinical scenarios of CRC in emergency are bowel obstruction and perforation. We propose treatment algorithms based on assessment of the patient's overall reserve and discuss the indications, techniques and impact of a stoma in the geriatric patient. Bridge to surgery strategies may be best adapted to help the frail geriatric patient overcome the acute disease and maybe return to previous state of function. Post-operative morbidity and mortality rates are high in emergency surgery for CRC, but if the geriatric patient survives the post-operative period, oncological prognosis seems to be similar to younger patients. Because the occurrence of complications is the strongest predictor of functional decline and death, post-operative care plays a major role to optimize outcomes. Future studies should further investigate emergency surgery of CRC in the older adults focusing in particular on functional outcomes in order to help physicians counsel patients and families for a tailored treatment.

A Simple Screening Tool to Predict Outcomes in Older Adults Undergoing Emergency General Surgery.

OBJECTIVES: To determine whether the Flemish version of the Triage Risk Screening Tool (fTRST) can be used to accurately assess frailty in an emergency setting. DESIGN: Prospective observational study. SETTING: of a tertiary referral hospital. PATIENTS: All individuals aged 70 and older consecutively admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 who met inclusion criteria (N=110). MEASUREMENTS: Individuals were screened with the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index and American Society of Anesthesiology score. Thirty- and 90-day postoperative complications where recorded. Regression analyses were performed to identify possible preoperative predictors of adverse outcomes. RESULTS: Thirty-day major complications (Clavien-Dindo Classification 3-5) occurred in 28.2% of participants (n=31). fTRST had the highest correlation with major complications (odds ratio (OR) = 7.42). All participants who died within 30 days of surgery has a fTRST score of 2 or greater (area under the receiver operating curve (AUC)=71.3). When risk factors for overall 90-day mortality were analyzed, a fTRST score of 2 or greater had sensitivity of 96% (95% confidence interval CI=79.6-99.9%), specificity of 43.5% (95% CI=32.8-54.7%) (AUC=69.8%; OR=18.50, 95% CI=2.39-143.11, p = .005). The average length of hospital stay was more than twice as long in the group with a fTRST score of 2 or greater (15.2 days) than in those with a score less than 2 (6.6 days) (p = .005). CONCLUSION: The fTRST is an effective tool to predict mortality, morbidity, and length of stay after emergency surgery and can therefore be used to anticipate postoperative course, determine care goals, and plan for involvement of a dedicated geriatric care team. J Am Geriatr Soc 67:309-316, 2019.

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.

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

INTRODUCTION: Bilateral adrenal myelolipoma is a rare benign neoplasm. We presented the case of a young man affected by a bilateral myelolipoma and the analysis of the literature of bilateral cases of myelolipoma. Our purpose is to give a suggestion of clear terms of reference regarding the management of this kind of bilateral neoplasm. PRESENTATION OF CASE: We reported the case of a 41-year-old healthy man complained of abdominal pain in the upper quadrants. No significant alterations were found in routine blood and endocrinological tests. The imaging (CT and MRI) showed a huge right adrenal mass and a smaller lesion at the left adrenal gland. The preoperative pathological characterization was suggestive for a myelolipoma. A right open adrenalectomy was performed, and a radiological surveillance was planned for the left tumor. The pathological exam confirmed the diagnosis. DISCUSSION: In literature, there are 36 cases described. The clinical presentation consisted of symptomatic tumors, incidentally diagnosed lesions or myelolipomas in patients with an associated endocrinal disorder. Symptomatic tumors or those bigger than 7cm, because of the potential risk of rupture, are usually treated surgically. In smaller (<7cm) and asymptomatic ones the surgical treatment is not univocal. CONCLUSION: In the setting of the surgical treatment, it is important to preserve in some way the hormonal function. For that reason, the bilateral adrenalectomy has to be reserved for symptomatic or sizeable (>7cm) cases. As far as we know, this is the first review on bilateral myelolipomas.

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.

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.

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.

Has breast cancer in the elderly remained the same over recent decades? A comparison of two groups of patients 70years 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.

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.

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.

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.

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 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.