Antonio Manenti

Myeloperoxidase-Positive Cell Infiltration in Colorectal Carcinogenesis as Indicator of Colorectal Cancer Risk

Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in ×100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean ± SD, 2.7 ± 2.0 versus 1.4 ± 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 ± 15.5 versus 11.9 ± 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2291–7)

Aberrant crypt foci in patients with colorectal cancer

Aberrant crypt foci (ACF) are clusters of abnormally large colonic crypts identified on the mucosal surface of the human colon. They are thought to be preneoplastic lesions. The aim of the present study was to compare density (number of ACF per square cm of mucosal surface), crypt multiplicity (number of crypts per ACF) and histology of ACF in colonic resections of colorectal cancer patients resident in two Italian provinces with a twofold difference in colorectal cancer incidence rates. Thirty-two and 26 colonic resections were collected after operation in Ragusa (Southern Italy) and Modena (Northern Italy), respectively, and fixed in 10% formalin. Mucosal layers were observed under a light microscope at 25x after staining with methylene blue. Density of ACF was significantly higher in Modena (median 0.101 ACF cm(-2)) than in Ragusa (0.049, P = 0.001), whereas there was no difference in crypt multiplicity. ACF were classified into three groups according to histological features: ACF with mild alterations (hypertrophic ACF, 73%), ACF with hyperplasia (hyperplastic ACF, 17%) and ACF with dysplasia (microadenomas, 10%). The proportions of ACF in the three groups were similar in the two provinces. Density of ACF was higher and crypt multiplicity lower proceeding from proximal to distal large bowel. Microadenomas were observed only in the colon, whereas hyperplastic ACF were more frequent in the rectum. In conclusion, density of ACF correlates with colorectal cancer rates in two Italian provinces, and shows a positive gradient from proximal to distal large bowel. Histology of ACF suggests that they may be precursors of both hyperplastic and adenomatous polyps. These data provide further evidence of the role of ACF in human colorectal carcinogenesis.

Laparoscopy in routine and emergency surgery: Experience with 1,720 cases

Experience with laparoscopy in 1,720 cases performed for surgical diseases with elective or emergency indications is reported. It is hoped that laparoscopy, a simple and harmless technic of great diagnostic value, will be employed more frequently in routine and emergency surgery.

Altered Expression of Apoptosis Biomarkers in Human Colorectal Microadenomas

Human colorectal microadenomas are considered the earliest detectable premalignant lesions in the colon. They can be identified as aggregates of enlarged crypts with thicker epithelial linings and elongated luminal openings on the colonic mucosal surface after methylene blue staining and observation under a dissecting microscope. Multiple lines of evidence suggest that a central role in neoplastic development is played by the inhibition of apoptosis, followed by disruption of DNA repair. Understanding the early mechanisms of colorectal carcinogenesis may help develop new approaches of colorectal cancer prevention and treatment. The aim of the present study was to quantify poly-ADP ribose polymerase 1 (PARP-1)–positive cells and to evaluate apoptotic control mechanisms through Caspase-3 active and Bcl-2 protein expression in human microadenomas and in normal colorectal mucosa using immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments. The mean percentage of PARP-1–positive epithelial cells was 3.0 ± 0.37% (SD) and 15.67 ± 0.40% in microadenoma and in normal mucosa, respectively. Proteins involved in programmed cell death were differently expressed in microadenoma and in normal mucosa. Indeed, by semiquantitative immunoflourescence analysis, confirmed by Western blot, microadenoma showed high levels of Caspase-3 active and low levels of Bcl-2 expression, whereas the opposite was true for normal colorectal mucosa. In the stroma of normal colorectal mucosa, fibroblast-like cells and neutrophils were the cells that underwent apoptosis to a greater extent. In conclusion, malfunction of the control mechanisms of programmed cell death seems present in the early stages of colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 19(2); 351–7

Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells.

Radiotherapy-induced mesorectum alterations: histological evaluation of 90 consecutive cases

Abstract Objective. In order to identify the radiotherapy-induced histological modifications in the mesorectum, we reviewed the surgical specimens of 90 rectal resections comprehensive of the total mesorectal excision (23 cases radiologically classified as cT2N0M0 and 67 as cT3N0M0). All patients were preoperative treated with radiotherapy: 20 with 50 Gy, 20 with 20 Gy and 50 Gy irradiation associated to FOLFOX scheme chemotherapy. Material and methods. Routine hematoxylin and eosin stained serial slides at 5 mm of intervals were obtained from surgical specimens and included the tumor site and the adjacent irradiated mucosa, the submucosa and the muscular layers of the rectal wall and the mesorectal adipose tissue, completely removed until to the mesorectal fascia. Ten subjects (eight cT2N0M0 and two cT3N0M0), who did not received preoperative oncological treatments were adopted as controls. Results. Histologically, examination revealed fibrosis of the adipose tissue in 86 cases (95%), vascular damage including vasculities and fibrotic thickening wall of arteries and veins in 46 cases (51%), sclero-hyalinosis of lymph nodes with pericapsular fibrosis in 22 cases (23%) and perineural deposition of fibrosis in 12 (13%). These findings were ubiquitously observed in the whole mesorectum. Fibrosis of the adipose tissue and vasculitis were mainly associated to the combination of 50 Gy radiations plus chemotherapy (p < 0.05). Conclusion. The detection of histopathological alterations in the mesorectum can give reason of the well-known postoperative complications and long-term sequels.

Stem Cells Transplantation in Myocardial Tissue Induces Pro-arrhythmic Effects and Promotes Reperfusion. Comparison between Intramyocardial and Intravenous Approach

Ischemic heart disease is a life threatening condition whose prognosis remains poor as current treatments are palliative and the loss of cardiac tissue is not restored. Stem cell therapy appears to be a promising option for myocardial repair after myocardial infarction (MI). Recent experimental and clinical work has suggested that stem cell therapy contributes to cardiac regeneration and improve myocardial function. Unfortunately, there is still a lack about important issues such as mechanism of action of stem cells, dose, long-term engraftment, route of delivery and frequency of cell administration. Also, there is a concern about proarrhythmic effect of stem cell therapy. Some studies have provided basis that stem cells can show intrinsic pacemaker function and provide areas of slowed conduction that can set the stage for arrhythmias.

Energy drink overconsumption can trigger atrial fibrillation

To the Editor Many adverse cardiac effects have been reported following energy drinks consumption, among which atrial arrhythmias, acute coronary syndromes, and even cardiac arrest. These can develop also in the absence of other symptoms related to acute toxicity, such as neurological symptoms. Considering the absence of specific toxicological tests, the diagnosis of energy drink intoxication still remains clinical.

For a clearer comprehension of the lymphatic system in perihilar cholangiocarcinoma

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Image-Guided Proper Liver Segmentectomy

BackgroundThe new cross-sectional radiological tools, 3D computed tomography and magnetic resonance, allow a precise study of the liver anatomy. Thanks to these imaging techniques, a new space inside the liver parenchyma, the “hepatic core,” was recently recognized, where the hila of liver segments are present.MethodsOn the basis of anatomical and radiological observations, we identified a new virtual plane of dissection, named “hepato-portal,” which is useful in liver segmentectomy, if integrated with the classical planes of dissection.ResultsSimulated surgical procedures can be intra-operatively transferred by ultrasounds. In this way, we performed ten “proper” liver segmentectomies through preliminary sections of the hilar vessels and a precise dissection of the boundaries of each segment.ConclusionsOur experience underlines the value of integrating anatomy and radiology in the simulated liver surgery.