Federico Ghignone

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.

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.

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.

Positive predictive value of breast lesions of uncertain malignant potential (B3): Can we identify high risk patients? The value of a multidisciplinary team and implications in the surgical treatment

BACKGROUND AND AIM The use of conventional needle core biopsy for palpable masses and vacuum-assisted needle core biopsy for microcalcifications has significantly increased the preoperative diagnosis rate, but the strategy for those patients with lesions of uncertain malignant potential (B3) still remains controversial. The aim of this study was to evaluate the positive predictive value (PPV) of the malignancy of B3 lesions in order to establish their correct management in the setting of a multidisciplinary care pathway. METHODS Data from all patients who had a Needle Core Biopsy (NCB) or a Vacuum-Assisted Needle Core Biopsy (VANCB) between 2005 and 2014 were retrospectively collected and analyzed. The B3 patients were discussed by the Multidisciplinary Team (MDT) deciding for surgery or for follow-up, based on a score in which clinical-instrumental factors and environmental factors were considered. The PPV of malignancy of all surgically excised B3 lesions was calculated. RESULTS One hundred and seventy-eight B3 NCBs were included in the study and Atypical Epithelial Proliferation of Ductal Type (AEDPT) was the most represented subcategory. The final histopathology report of the 128 patients operated on showed 94 benign and 34 malignant lesions. The PPV of B3 patients referred to surgery was 26.5%. CONCLUSION B3 patients should be evaluated by a breast MDT in order to make the right therapeutic decision, in particular for patients with contrasting clinical/diagnostic findings. Larger prospective studies are required to assess the definitive PPV of each B3 subcategory.

Possible Gender-Related Modulation by the ROCK1 Gene in Colorectal Cancer Susceptibility

Aim: In view of accumulating evidence supporting a pivotal role of the Rho/ROCK pathway in cancer, we investigated Rho-kinase polymorphisms as potential susceptibility factors in colorectal cancer (CRC) in a representative sample of the Italian population. Methods: DNA obtained from the peripheral blood samples of 137 CRC patients and 141 healthy controls was genotyped for four ROCK1 (rs35996865; rs73963110; rs2127958; rs288980) and five ROCK2 (rs12692437; rs7563468; rs35768389; rs17463896; rs16857265) selected single nucleotide polymorphisms. Results: None of the allelic variants of the nine selected markers was associated with the occurrence of CRC or with the development of regional lymph node metastasis. By contrast, the ROCK1 rs35996865 G variant allele was significantly more frequent in male patients (p = 0.028) than in the control group. Conclusion: This finding is, at present, the first that points to a possible gender-related modulation by the ROCK1 gene in CRC susceptibility.

Can POSSUM accurately predict post-operative complications risk in patients with abdominal Crohn's disease?

Although the majority of patients with Crohns disease (CD) are young, they are often seriously ill when surgery is required. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a risk prediction scoring system estimating 30‐day complications. The primary endpoint was to evaluate POSSUM efficacy in this subgroup. The secondary endpoint was to determine any potential correlation between POSSUM, Harvey–Bradshaw Index (HBI), length of stay (LOS) and anastomotic leak.

Attitudes of Surgeons toward Elderly Cancer Patients: A Survey from the SIOG Surgical Task Force

Cancer care in elderly patients is complex. A recent survey showed that among mostly academic surgeons, practice patterns varied in the care of elderly patients. The authors suggested three areas of intervention in improving care of this population: frailty assessment, nutritional assessment, and assessment of quality of life.

Contents Vol. 82, 2015

Founded 1938 as ‘Schweizerische Zeitschrift für allgemeine Pathologie und Bakteriologie’ by A. v. Albertini, A. Grumbach and H. Mooser, continued as ‘Pathologia et Microbiologia’ (1960–1975) and ‘Experimental Cell Biology’ (1976–1989); incorporating ‘Pathology and Immunopathology Research’, founded 1982 as ‘Survey and Synthesis of Pathology Research’ by J.M. Cruse and R.E. Lewis, continued as ‘Pathobiology’, edited by J.M. Cruse and R.E. Lewis (1990–1998) Continued by Ch. Wittekind (1999–2004)

Small bowel obstruction caused by a large B-cell lymphoma in a patient with multicentric Castleman’s disease: An unusual occurrence

Multicentric Castleman’s disease is a rare condition of systemic nonclonal lymph node hyperplasia. Because of its strong association with human herpes virus 8 (HHV8), the multicentric, more aggressive, form may progress to Kaposi sarcoma or non-Hodgkin lymphoma. While surgery is curative in the treatment of localized Castleman’s disease, operative treatment of the diffuse form has as yet been unsatisfactory. We report the case of a patient presenting with postprandial vomiting of 1 month duration consistent with partial small bowel obstruction secondary to terminal ileum intussusception. Resection of the small bowel showed a stenosing tumor triggering the intussusception. On pathological examination, the tumor was found to be composed of HHV8-positive plasmablastic lymphoma cells. To our knowledge, this represents the first case of a complication due to the progression of multicentric Castleman’s disease requiring surgical intervention for intussusception.