Diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas. An Useful Update with a Noteworthy Tip.

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Comparing laparoscopic surgery with open surgery for long-term outcomes in patients with stage I to III colon cancer.

BACKGROUND: Although the short-term advantages of laparoscopy for colon cancer (CC) over open surgery have been clearly demonstrated, there is little evidence available concerning the long-term outcomes. This study aimed to compare the long-term results of laparoscopic surgery versus open surgery in a cohort of CC patients from a single center. METHODS: A series of 443 patients consecutively operated on for stage I to III CC between January 2006 and December 2013 were followed up. Patients were divided into two groups according to the surgical technique and were compared for disease-free survival (DFS) and overall survival (OS) before and after 1:1 propensity score matching. RESULTS: Due to exclusions and drop-outs, the statistical analysis of the study is based on 398 patients. Open surgery was performed in 133 patients, and laparoscopic surgery was performed in 265. After propensity score matching, two comparable groups of 89 patients each were obtained. The 5-year DFS was 64.3% and 78.2% for patients in the open and laparoscopic resection groups, respectively [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.33-1.19; P = 0.148]. A 5-year OS of 72.1% and 86.8% was observed in the open and laparoscopic resection groups, respectively (HR 0.43, 95%CI 0.20-0.94; P = 0.026). The multivariate survival analysis demonstrated better results of laparoscopy compared with open surgery for both DFS (HR 0.43, 95%CI 0.23-0.78; P = 0.004) and OS (HR 0.28, 95%CI 0.14-0.59; P < 0.001). CONCLUSIONS: Despite the limitations of a retrospective analysis, our study confirms better results for laparoscopic surgery in terms of DFS and OS compared with open surgery in CC treatment.

hERG1 behaves as biomarker of progression to adenocarcinoma in Barrett's esophagus and can be exploited for a novel endoscopic surveillance.

Barrett's esophagus (BE) is the only well-known precursor lesion of esophageal adenocarcinoma (EA). The exact estimates of the annual progression rate from BE to EA vary from 0.07% to 3.6%. The identification of BE patients at higher risk to progress to EA is hence mandatory, although difficult to accomplish. In search of novel BE biomarkers we analyzed the efficacy of hERG1 potassium channels in predicting BE progression to EA. Once tested by immunohistochemistry (IHC) on bioptic samples, hERG1 was expressed in BE, and its expression levels increased during progression from BE to esophageal dysplasia (ED) and EA. hERG1 was also over-expressed in the metaplastic cells arising in BE lesions obtained in different BE mouse models, induced either surgically or chemically. Furthermore, transgenic mice which over express hERG1 in the whole gastrointestinal tract, developed BE lesions after an esophago-jejunal anastomosis more frequently, compared to controls. A case-control study was performed on 104 bioptic samples from newly diagnosed BE patients further followed up for at least 10 years. It emerged a statistically significant association between hERG1 expression status and risk of progression to EA. Finally, a novel fluorophore- conjugated recombinant single chain variable fragment antibody (scFv-hERG1-Alexa488) was tested on freshly collected live BE biopsies: it could recognize hERG1 positive samples, perfectly matching IHC data.Overall, hERG1 can be considered a novel BE biomarker to be exploited for a novel endoscopic surveillance protocol, either in biopsies or through endoscopy, to identify those BE patients with higher risk to progress to EA.

The esophageal microbiota in health and disease.

The esophageal mucosa is among the sites colonized by human microbiota, the complex microbial ecosystem that colonizes various body surfaces and is increasingly recognized to play roles in several physiological and pathological processes. Our understanding of the composition of the esophageal microbiota in health and disease is challenged by the need for invasive sampling procedures and by the dynamic nature of the esophageal environment and remains limited in comparison with the information available for other body sites. Members of the genus Streptococcus appear to be the major components of the microbiota of the healthy esophagus, although the presence of several other taxa has also been reported. Dysbiosis, consisting of enrichment in some Gram-negative taxa (including Veillonella, Prevotella, Haemophilus, Neisseria, Campylobacter, and Fusobacterium), has been reported in association with gastroesophageal reflux disease and is hypothesized to contribute to the evolution of this condition toward Barrett's esophagus (which is the most common esophageal precancerous lesion) and, eventually, adenocarcinoma. Some Campylobacter species (mostly C. concisus) are also putatively involved in the progression of disease toward adenocarcinoma. However, variable findings have recently been reported in additional studies. Causative relationships between dysbiosis or specific bacterial species and esophageal diseases remain controversial and warrant further investigations.

Hepatocellular carcinoma with osteoclast-like giant cells: report of the seventh case in the literature.

Hepatocellular carcinoma with osteoclast-like giant cells is extremely rare, and only six cases have been previously reported. Its histogenesis is at the moment controversial. The authors report a case of hepatocellular carcinoma with osteoclast-like giant cells found in a 74-year-old woman. The patient came with a dull pain in the right upper abdominal quadrants due to a liver neoplasm described at CT scan. A wedge resection of the fifth hepatic segment with appendectomy, omentectomy, and debulking of the major peritoneal implants was performed. Histologically, the diagnosis of hepatocellular carcinoma with high grade differentiation associated with giant osteoclast-like cells was done without any evidence of hepatitis or cirrhosis in the surrounding hepatic parenchyma. Immunohistochemistry was positive for CD10 and CD68 and in situ hybridization revealed the expression of receptor activator of nuclear factor-kappa B (RANK) in the giant cells and receptor activator of nuclear factor-kappa B ligand (RANKL) in the tumor cells.

Chylous mesenteric cysts: a rare surgical challenge.

A mesenteric cyst is defined as a cyst that is located in the mesentery of the gastrointestinal tract and may extend from the base of the mesentery into the retroperitoneum. It is often asymptomatic and therefore it is usually found as an incidental finding. Preoperative diagnosis may be possible with computed tomography and magnetic resonance imaging. However, the correct diagnosis can only be made with histology. The first-choice therapy is the complete removal of the cyst, which must be accurately planned according to the anatomy of the lesion, its dimensions and its relationships with major abdominal structures. We present two clinical cases: the one of a 30-year-old man with a mesenteric cyst that was removed by laparoscopy and the other of a 61-year-old woman who underwent open excision of a huge retroperitoneal cyst.

Histological and Ultrastructural Effects of Ultrasound-induced Cavitation on Human Skin Adipose Tissue.

BACKGROUND: In aesthetic medicine, the most promising techniques for noninvasive body sculpturing purposes are based on ultrasound-induced fat cavitation. Liporeductive ultrasound devices afford clinically relevant subcutaneous fat pad reduction without significant adverse reactions. This study aims at evaluating the histological and ultrastructural changes induced by ultrasound cavitation on the different cell components of human skin. METHODS: Control and ultrasound-treated ex vivo abdominal full-thickness skin samples and skin biopsies from patients pretreated with or without ultrasound cavitation were studied histologically, morphometrically, and ultrastructurally to evaluate possible changes in adipocyte size and morphology. Adipocyte apoptosis and triglyceride release were also assayed. Clinical evaluation of the effects of 4 weekly ultrasound vs sham treatments was performed by plicometry. RESULTS: Compared with the sham-treated control samples, ultrasound cavitation induced a statistically significant reduction in the size of the adipocytes (P < 0.001), the appearance of micropores and triglyceride leakage and release in the conditioned medium (P < 0.05 at 15 min), or adipose tissue interstitium, without appreciable changes in microvascular, stromal, and epidermal components and in the number of apoptotic adipocytes. Clinically, the ultrasound treatment caused a significant reduction of abdominal fat. CONCLUSIONS: This study further strengthens the current notion that noninvasive transcutaneous ultrasound cavitation is a promising and safe technology for localized reduction of fat and provides experimental evidence for its specific mechanism of action on the adipocytes.

Barrett's esophagus: genetic and cell changes.

The following includes commentaries on how genetic code of Barrett's esophagus (BE) patients, the mechanisms for GERD-induced esophageal expression of caudal homeobox, and the development of Barrett's metaplasia are increasingly better known, including the role of stromal genes in oncogenesis. Additional lessons have been learned in vitro models in nonneoplastic cell lines, yet there are limitations to what can be expected from BE-derived cell lines. Other topics discussed include clonal diversity in Barrett's esophagus; the application of peptide arrays to clinical samples of metaplastic mucosa; proliferation and apoptosis of Barrett's cell lines; tissue biomarkers for neoplasia; and transcription factors associated with BE.

Barrett's esophagus: endoscopic diagnosis.

This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Barrett's esophagus: histology and immunohistology.

The following on histology and immunohistology of Barrett's esophagus (BE) includes commentaries on the various difficulties remaining in reaching a consensus on the definition of BE; the difficulties in the characterization of intestinal and cardiac mucosa, and in the role of submucosal glands in the development of BE; the importance of a new monoclonal antibody to recognize esophageal intestinal mucosa; the importance of pseudo goblet cells; the best techniques for the endoscopic detection of Barrett's epithelium; and the biomarkers for identification of patients predisposed to the development of BE.

Barrett's esophagus: proton pump inhibitors and chemoprevention I.

The following on proton pump inhibitors and chemoprevention in Barrett's esophagus includes commentaries on normalization of esophageal refluxate; the effects of 5-HT(4) agonists on EGF secretion and of lubripristone on chloride channels agents; the role of Campylobacter toxin production; the deleterious effects of unconjugated bile acids; the role of baclofen in nonacid reflux; the threshold for adequate esophageal acid exposure; the effects of proton pump inhibitor (PPI) therapy on normalization of esophageal pH and on cell proliferation; the role of the phenotype of cellular proliferation on the effects of PPI therapy; and the value of Symptom Index and Symptom Association Probability in the evaluation of potential response to treatment.

Barrett's esophagus: proton pump inhibitors and chemoprevention II.

The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs.

Expression of estrogen receptor beta in colon cancer progression.

Colon cancer is the most frequent neoplasia of the intestine. This pathology is the third highest cause of death from cancer with 430,000 deaths globally per year. Estrogen has also been implicated in the development and progression of colon cancer. Also sex-specific differences have been suggested to be involved in the process. Previous studies have shown the estrogen beta receptor to be the dominant receptor type in normal colonic tissue and its down-regulation along with the progression of colorectal cancer. The presence of estrogen receptors and products of estrogen-related genes in the colon suggests that estrogens have direct effects on the colonic tissue. However, the specific effect of estrogens on a normal colon and the role in the colon carcinogenesis are far from clear. The aim of this study is to analyze by real-time polymerase chain reaction, the relative quantitative expression of the estrogen receptors beta, beta1, beta2, and beta5 in colon adenocarcinomas and to compare this expression with the respective in normal tissues. Moreover, we evaluate a possible correlation between estrogen's receptor expressions and disease stages. Normal tissues show estrogen receptor beta expression greater than pathologic tissues and the estrogen receptor beta result as most expressed in the lower disease stages.

NF2 expression levels of gastrointestinal stromal tumors: a quantitative real-time PCR study.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. Until today, there have been few markers specific for the tumor. This has complicated the differential diagnosis of the neoplasm from tumors of smooth muscle origin. Recently, the proto-oncogene c-kit has been shown to be a very relevant marker as it almost invariably is expressed in gastrointestinal stromal tumors. Radiation exposure, hormonal and genetic factors, particularly neurofibromatosis 2, have been implicated in their development and growth. GIST initiation, either in NF2-associated or in sporadic cases, is linked to inactivation of members of the proteins 4.1 superfamily. The majority of the mutations identified in the NF2 gene result in a truncated protein and are clinically associated with a severe phenotype. Occasionally, missense mutations associated with a mild phenotype may occur. We compared NF2 gene expression in 5 cases with gastrointestinal stromal tumors by quantitative real-time polymerase chain reaction analysis. NF2 gene mRNA expression was assessed in fresh tissue of stomach from 5 consecutive patients. We detected no alterations in NF2 gene expression in the quantitative analyses of the 5 tumors.

TNM staging and T-cell receptor gamma expression in colon adenocarcinoma. Correlation with disease progression?

AIMS AND BACKGROUND: Colorectal cancer is the second most common cause of cancer-related death in Europe and the United States. Several studies have evaluated the immune response to colorectal cancer, with contradictory results. Some studies showed that lymphocyte infiltration in colorectal cancer seemed to be an important prognostic parameter, a finding not confirmed by other studies. Several studies showed the gamma-delta T-cell receptor repertoire of intestinal adenocarcinoma. In this study, we hypothesize that the presence of T cells with the T-cell receptor gamma complex may play a particular role in carcinogenesis and tumor progression. METHODS: A total of 58 patients with colon adenocarcinoma was included in the analysis. We used the TNM staging system to grade colon cancer. RESULTS: Thirty samples (52.6%) revealed a polyclonal rearrangement of T-cell receptor gamma. In the NO cases, only 5 samples revealed a T-cell receptor gamma molecular assessment; in N1/N2 cases, 25 revealed a T-cell receptor gamma molecular assessment. CONCLUSIONS: The results showed statistical significance between the presence of T-cell receptor gamma and N1/N2 stage lymph nodes (P = 0.001).

Quantitative expression of the homeobox and integrin genes in human gastric carcinoma.

The homeobox (HOX) genes are a large family of regulator genes involved in the control of developmental processes and cell differentiation. The HOX genes encode transcription factors, and an increasing number of studies have shown that these genes may be implicated in the growth and the progression of many types of tumours. The present study investigated the expression of the HOX and integrin genes and their relationships in gastric carcinoma. We analyzed the RNA expression of 13 HOX genes from HOXA, C and D clusters and alphaV, alpha5 and alpha8 integrin genes in 24 gastric cancer samples by quantitative real-time PCR. The results showed that the HOXA2 gene and the alpha8 integrin gene had a lower expression in tumour samples than in normal gastric mucosas. The comparison between the HOX and integrin genes showed that HOXA2 and alphaV integrin expression presented the same trend in 83% of the samples. Moreover, in cancer samples that expressed the HOXD11 gene, the expression of alphaV integrin was lower with respect to normal mucosas. The different roles of HOX and integrin genes in gastric carcinoma remain to be fully elucidated. These findings suggest that the HOX genes may play a critical role in the genesis, maintenance and diffusion of gastric carcinoma.

Real-time PCR analysis of RNA extracted from formalin-fixed and paraffin-embeded tissues: effects of the fixation on outcome reliability.

In many pathologic circumstances, quantitative mRNA expression levels are important for evaluation of possible genome mutations. The development of real-time polymerase chain reaction (RT-PCR) technology has facilitated the realization of nucleic acid quantification. Potentially, quantitative PCR offers a number of advantages over traditional methods because it permits the use of small amounts of genetic material. In the present study, we optimize a RNA purification technique on specimens that are formalin-fixed, paraffin-embedded and we examine prolonged formalin fixation effects on quantitative RT-PCR analysis. We compared RNA levels with 70 colic mucosa samples using the cyclooxygenase 2 gene as marker. The difference in amplification successes between formalin-fixed tissues and formalin-fixed, paraffin-embedded tissues was not statistically significant. Moreover, we compared the expression of formalin-fixed samples with the expression of each fresh tissue. Wilcoxon Mann-Whitney test shows that only the difference in the expression levels of 1- or 3-hour formalin-fixed samples is not statistically significant with respect to other fixation times. We found that the mRNA can be reliably extracted from formalin fixed, paraffin-embedded tissue sections but that prolonged formalin fixation produces different results in quantitative RT-PCR. It can be related to difference in RNA sequences length and the generation of secondary structures that are more susceptible to the prolonged formalin fixation. We suppose that the paraffin do not influence the RNA extraction yield because there are no statistical significant differences between amplification success of formalin-fixed tissues and paraffin-embedded tissues. Therefore, in relative expression quantization, we confirm that it is appropriate to use specimens with same protocols and time for formalin fixation.

Expression of HOX homeobox genes in the adult human colonic mucosa (and colorectal cancer?).

We studied the expression of several homeobox genes of the HOX family in the adult human intestinal mucosa. HOX genes are regulatory genes homologous to the homeotic genes controlling the body plan of the fruit fly Drosophila melanogaster. The HOX genes are distributed in four homologous HOX loci termed HOX-A, B, C and D, located on four different chromosomes. They have been found to be expressed in many embryonic tissues and axial structures like the central nervous system, the spine and in selected adult cells. The expression of 39 HOX genes belonging to HOX-A, B, C and D was studied by in situ hybridization on specimens of mucosa from normal adult colon. All the genes studied were shown to be expressed in these tissues, but the genes belonging to the four loci showed different localization within the colonic mucosa: HOX-A genes are expressed in undifferentiated proliferating cells at the base of the crypts, HOX-C genes in differentiated cells at the apex of the crypts and HOX-B and HOX-D genes are weakly expressed along the entire crypt length. Expression of some of these genes was also studied in differentiating CaCo-2 cells and tumoral tissues. In particular, in colonic adenocarcinomatous cells, some HOX-A genes appear to be abundantly expressed confirming the presence of these gene products in normal.