Metabolic syndrome and risk of subsequent colorectal cancer

The metabolic syndrome and visceral obesity have anincreasing prevalence and incidence in the generalpopulation. The actual prevalence of the metabolicsyndrome is 24% in US population and between24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES , INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer. Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944 717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical signifi cance and may have profound health benefi ts on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.

Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer

Epithelial-to-mesenchymal transition(EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer(CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical(IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapyor radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMTangiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.

Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, N-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors

AIM To evaluate the immunohistochemical(IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition(EMT/MET), in gastrointestinal stromal tumors(GISTs). METHODS In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin,N-cadherin, SLUG, V-set and immunoglobulin domain containing 1(VSIG1) and CD44. RESULTS The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for N-cadherin. No correlation was noted between the examined markers and clinicopathological parameters. Nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors(e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for N-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity(P = 0.01) and nuclear positivity for SLUG and/or CD44. CONCLUSION GIST aggressivity may be induced by nuclear upregulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not N-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.

Difficulties in diagnosing anorectal melanoma: A case report and review of the literature

BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation.Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established.Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.CASE SUMMARY A 66-year-old woman presented with intermittent anal bleeding,pain,and tenesmus in the past month,with no associated weight loss.Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm,with exulcerated areas and an adherent clot but without obstruction.Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis.Tumour markers CA 19-9 and CEA were within the normal range.After 6 mo,due to the persistence of symptoms,a pelvic magnetic resonance imaging scan was performed.A lesion measuring 2.8 cm×2.7 cm×2.1 cm was identified at the anorectal junction,along with two adjacent lymphadenopathies.No distant metastases were detected.Immunohistochemistry was performed on the second set of biopsies,and a diagnosis of anorectal melanoma was established.Surgical treatment by abdominoperineal resection was performed.Evolution was marked by the appearance of lung metastases at 1 mo postoperatively,detected on a positron emission tomography-computer tomography scan,and perineal recurrence after 5 mo.After molecular testing,the patient was included in an immunotherapy trial.CONCLUSION This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma,the importance of performing histological analysis on a wellrepresented biopsy specimen,and the poor prognosis,even with radical surgery.

Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: Report of two cases

Mixed adenoneuroendocrine carcinoma(MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor. To date, only seven cases have been reported in the cecum, and less than 40 in the stomach. Our first case was diagnosed in a 74-years-old female as a polypoid lesion of the cecum with direct invasion in the transverse colon, without lymph node metastases. The second case was diagnosed in the stomach of a 46-years-old male as a polypoid tumor of the antral region that invaded the pancreas and presented metastases in 22 regional lymph nodes. The metastatic tissue was represented by the glandular component. In both cases, the tumor consisted of a moderately-differentiated tubular adenocarcinoma(with mucinous component in Case 1) intermingled with neuroendocrine carcinoma. Ki67 index was lower than 20% in Case 1, respectively higher than 20% in Case 2. The neuroendocrine component was marked by synaptophysin and neuron specific enolase, being negative for Keratins 7/20. The neuroendocrine component represented 60% in Case 1, and 40% in Case 2, respectively. The glandular components were marked by carcinoembryonic antigen, maspin and keratin 20/7(Case 1/2). Both cases were proved to be microsatellite stable. Independently by the localization and tumor stage, MANECs appear to be highly malignant tumors, with high risk for distant metastases. The aggressiveness seems to depend on the endocrine component, independent of its proportion. The neuroendocrine component could be a dedifferentiated adenocarcinoma with a neuroendocrine phenotype.

Single skip metastasis in sentinel lymph node: In an early gastric cancer

Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical protocol.In this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral region.Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer.An incidentally detected blue-stained lymph node located along the middle colic artery was also removed.This was detected 40 min after injection of the methylene blue.Histopathologic examination showed a p T1b-staged well-differentiated HER-2-negative adenocarcinoma.All of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor cells.The only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph node.This incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after surgery.In this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.

Cystic jejunal duplication with Heinrich's type Ⅰ ectopic pancreas, incidentally discovered in a patient with pancreatic tail neoplasm

The aim of this study was to present a case of enteric duplication cyst and criteria for a proper differential diagnosis. A 51-year-old male was hospitalized for pancreatic tail neoplasm and distal pancreatectomy with splenectomy was performed. During surgery, a jejunal cystic lesion was incidentally detected and jejunectomy was performed. Microscopically, the cyst was observed to be covered by Keratin 7/Keratin 20 positive intestinal type epithelium and the muscularis layer was shared by the cyst and adjacent jejunum, without a cleavage plane between the cyst wall and jejunal muscularis propria. In the deep muscularis propria, a Heinrich's type Ⅰ ectopic pancreas was also noted. In the pancreatic tail, a low grade intraepithelial lesion(panIN-1a) was diagnosed. This case highlights the necessity for a correct differential diagnosis of such rare lesions. Roughly 30 cases of jejunal duplication cysts have been reported to date in the PubM ed database.