Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Anoplasty for anatomical anal stenosis: systematic review of complications and recurrences.

AIM: The optimal surgical treatment for anatomical anal stenosis (AS) remains to be determined. The aim of this study was to determine the rates of complications and recurrence after anoplasty for anatomical AS and, wherever feasible, compare the outcomes for the various techniques. METHOD: A PROSPERO-registered systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medline, PubMed, Embase, Cochrane Library of Systematic Review, Scopus and Web of Science were searched for articles published up to May 2021. Studies that assessed the outcomes of anoplasty in adult patients with anatomical AS were selected. The primary outcomes were complications and recurrence. The methodological quality of studies was appraised using the Joanna Briggs Institute critical appraisal tools. RESULTS: From the total of 2705 unique screened records, 151 were assessed for eligibility. Only 29 studies (two prospective) met the inclusion criteria, reporting data on 556 patients [mean age 53 (18-83) years, 46% female]. Previous history of surgery for haemorrhoidal disease accounted for three quarters of cases. A total of 14 types of anoplasty were found, with the Y-V flap being the most performed technique [27% of cases (n = 149)]. Complications frequently occurred, with a pooled prevalence of 10.2% (95% CI 3.9%-24.1%) after Y-V flap and 11.5% (5.3%-23.0%) after rhomboid/diamond flap. Patients undergoing house flap achieved better results in terms of clinical improvement, satisfaction and quality of life compared with Y-V flap and rhomboid/diamond flap. When considering only studies with at least 12 months of follow-up, the pooled prevalence of recurrence was 4.7% (2.2%-9.8%), with significantly higher rates observed in the prospective versus retrospective series [pooled prevalence 18.9% (11.5%-29.5%) vs. 3.6% (1.7-7.8%), respectively; p < 0.001]. CONCLUSION: Both complications and recurrence were significantly lower after house flap compared with rhomboid/diamond and Y-V flap. Better designed multicentre studies with longer follow-up are needed to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42021239493.

Transanal reinforcement of low rectal anastomosis versus protective ileostomy after total mesorectal excision for rectal cancer. Preliminary results of a randomized clinical trial.

AIM: The study aimed to show if transanal reinforcement of the suture line can prevent anastomotic leakage (AL) after rectal cancer surgery, thus avoiding the need for a covering ileostomy. METHODS: This is a prospective, multicentre, parallel-arm randomized controlled equivalence trial. After standard total mesorectal excision, patients with anastomotic line at 1-3 cm from the dentate line were randomized to have transanal suture reinforcement (TAR group) or protective ileostomy (PI group). RESULTS: Twenty-nine patients had PI, 25 had TAR. The two groups were comparable both for baseline characteristics and intra-operative aspects. Clinically evident AL occurred in four (16%) and five (17.24%) patients of the TAR and PI group, respectively, resulting in a difference of -1.20% (90% CI -17.93, 15.45), while subclinical AL at proctography was absent in 15 (65.22%) and 13 (50%) patients of the TAR and PI groups, respectively, resulting in a difference of 15% (90% CI -7.74 to 38.17). CONCLUSION: Preliminary data suggest that transanal reinforcement of the suture line performed in rectal cancer patients with suture line at 1-3 cm from the dentate line carries a similar (even if not equivalent) AL rate to covering ileostomy, suggesting that a covering ileostomy could be avoided in this selected group of patients. This indication needs to be addressed with future larger trials (clinicaltrials.gov ID number NCT02279771).

Efficacy of cyanoacrylate in the prevention of delayed bleeding after endoscopic mucosal resection of large colorectal polyps: a pilot study.

BACKGROUND: Postoperative bleeding is a common complication after endoscopic polypectomy, particularly after endoscopic mucosal resection (EMR) of large non-pedunculated polyps, despite prophylactic clipping can reduce its occurrence. Cyanoacrylate glue has recently been proposed as a useful tool in reducing bleeding in surgery because of its adhesive and haemostatic properties. The aim of this study is to evaluate the usefulness of endoscopic application of a modified cyanoacrylate glue in the prevention of early or delayed post EMR bleeding. METHODS: This is a pilot study. Inclusion criteria were patients between 18 and 75 years old affected by sessile or flat colonic polyps larger than 2 cm. Patients enrolled in the study were randomized in two groups: group A (EMR) and group B (EMR with the application of 0.3 ml of N-butyl-2-cyanoacrylate + methacryloxysulfolane-Glubran 2®). RESULTS: Fifteen patients in both group A and B were enrolled. There were no intraoperative complications but haemostatic clipping was necessary in 3 patients in each group because of active bleeding. Delayed (after 24 h) bleeding occurred in two patients (13.3%) in group A requiring hospital readmission and re-do endoscopy with apposition of haemostatic clips. No case of bleeding was recorded in group B (p = 0.48). CONCLUSION: The results of this pilot study suggest a potential role of local spray application of Glubran®2 in reducing post-procedural bleeding.

Laparoscopic liver resection in elderly patients: systematic review and meta-analysis.

Laparoscopic liver resection (LLR) is becoming standard practice, replacing the open approach in terms of safety and feasibility. However, few data are available for the elderly. The objective of this study is to assess the feasibility of LLR in elderly patients, by making a comparison with open liver resection (OLR) and with non-elderly patients. Relevant studies found in the Cochrane Library, Embase, PubMed, and Web of Science were used in order to perform a systematic review and meta-analysis. Nine fully extracted comparative studies were included and two groups were identified: Group 1 with a comparison between OLR and LLR in the elderly and Group 2 with a focus on differences after LLR between elderly and non-elderly patients. A total number of 497 elderly patients who underwent LLR were analyzed. A random effect model was used for the meta-analysis. In Group 1, 1025 elderly patients were included: 640 underwent OLR and 385 underwent LLR. LLR was associated with minor blood loss (MD - 240 mL, 95% CI - 416.61, - 63.55; p 0.008; I2 = 96%), less transfusion (8% vs. 13.1%; RR 0.61, 95% CI 0.41, 0.91; p = 0.02; I2 = 0%), fewer postoperative Clavien-Dindo III/IV complications (RR 0.48 in favor of LLR; 95% CI 0.29, 0.77; p = 0.003; I2 = 0%). On the other hand, no significant difference was observed in terms of bile leakage, ascites, mortality, liver failure, or R0 resection. Group 2 included 112 elderly and 276 non-elderly patients who underwent LLR. The meta-analysis showed no significant difference in terms of blood loss, transfusions, liver failure, Clavien-Dindo III/IV complications, postoperative mortality, ascites, bile leak, hospital stay, R0 resection, and operative time. Laparoscopic liver resection is a safe and feasible procedure for elderly patients. However, further randomized studies are required to confirm this.

Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer.

Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization.

Staple line reinforcement with nebulized cyanoacrylate glue in laparoscopic sleeve gastrectomy: A propensity score-matched study.

BACKGROUND: A dreaded complication of laparoscopic sleeve gastrectomy (LSG) is suture leak. The study aimed to assess the efficacy of the nebulized comonomer Glubran 2® (N-butyl-cyanoacrylate + metacrylosysolfolane) applied to the LSG staple line. METHODS: A propensity-matched comparison analysis was conducted in 125 patients undergoing LSG between 2017 and 2019. Groups included those treated with Glubran® (group 1, n = 70) and those without Glubran® treatment (group 2, n = 55). RESULTS: There were differences in the mean body mass index (44.4 vs 43 kg/m2; P < 0.05) between the groups. There was a non-significant increase in the operative time for group 1 compared with group 2 (97 ± 8 vs 93.8 ± 10.7 min; P = 0.07), with a greater amount of estimated blood loss (94.5 mL vs 87.8; P < 0.01). There were more severe complications in group 2 over group 1 cases (8 vs 0%; P < 0.05), although postoperative bleeding did not differ between the two groups (1.4 vs 5.4%). There were no postoperative leaks in group 1 patients, but there were two leaks in group 2 cases with an increased length of hospital stay in patients with a leak. CONCLUSION: Glubran® LSG support may reduce leak risk without increasing operating time.

Safety and Effectiveness of Tailored Hemorrhoidectomy in Outpatients Setting.

Introduction: Single or double prolapsed pile instead of full muco-hemorrhoidal prolapse is a common finding in patients with symptomatic III or IV degree hemorrhoids. For this selected group of patients, relief of symptoms could be achieved by managing the single/double prolapsed piles instead of performing traditional hemorrhoidectomy. The aim of this single-center study was to evaluate the safety and medium- and long-term effectiveness of an outpatient tailored Milligan-Morgan hemorrhoidectomy (MMH) performed under local anesthesia (LA). Material and methods: Clinical records of 202 patients submitted to outpatient tailored MMH, under LA and without anal dilation, treated between 2013 and 2020, were retrospectively reviewed using a prospectively maintained database and completed by a telephone interview or outpatient consultation. Postoperative pain score, the need for painkillers, postoperative complications and symptoms recurrence, return to working activities, and patient grading assessment scale were recorded. Results: Thirty-five (17%) out of 202 patients recruited were lost to the follow-up. One hundred and fifty-two and 15 patients underwent a single and double pile hemorrhoidectomy, respectively. With regard to postoperative outcomes, visual analogue scale (VAS) decreased from a median value of 4 [interquartile range (IQR) 2-6] on the day of surgery to 1 (IQR 0-4) on the 10th postoperative day (p < 0.001). Sixty-one patients (37%) needed oral painkillers during the 1st week after surgery. There was no mortality or major postoperative complication. Bleeding requiring hospital readmission was reported in seven (4%) patients, and one patient underwent emergency surgery with no need for blood transfusion. No postoperative urinary retention, anal incontinence, or stricture occurred in the series. During the median follow-up of 39 (IQR 12-60) months, 26 patients (16%) reported symptoms of recurrence but only six underwent traditional MMH. Recovery to normal activity occurred within a median period of 6 days (IQR 3-10) and the Clinical Patient Grading Assessment Scale (CPGAS) at 1 year after surgery was reported to be a "good deal better." Conclusions: Tailored MMH performed under LA in an ambulatory setting can be considered a safe and effective technique with high compliance and satisfaction of patients.

E-consensus on telemedicine in proctology: A RAND/UCLA-modified study.

BACKGROUND: Coronavirus disease 2019 is revolutionizing healthcare delivery. The aim of this study was to reach a consensus among experts as to the possible applications of telemedicine in the proctologic field. METHODS: A group of 55 clinical practice recommendations was developed by a clinical guidance group based on coalescence of evidence and expert opinion. The Telemedicine in Proctology Italian Working Group included 47 Italian Society of Colorectal Surgery nominated experts evaluating the appropriateness of each clinical practice recommendations based on published RAND/UCLA methodology in 2 rounds. RESULTS: Stakeholder median age was 53 years (interquartile range limits 40-60), and 38 (81%) were men. Nine (19%) panelists reported no experience with telemedicine before the pandemic. Agreement was obtained on a minimum of 3 to 5 years of practice in the proctologic field before starting teleconsultations, which should be regularly paid, with advice and prescriptions incorporated into a formal report sent to the patient by e-mail along with a receipt. Of the panelists, 35 of 47 (74%) agreed that teleconsultation carries the risk of misdiagnosis of cancer, thus recommending an in-person assessment before scheduling any surgery. Fifteen additional clinical practice recommendations were re-elaborated in the second round and assessed by 44 of 47 (93.6%) panelists. The application of telemedicine for the diagnosis of common proctologic conditions (eg, hemorrhoidal disease, anal abscess and fistula, anal condylomas, and anal fissure) and functional pelvic floor disorders was generally considered inappropriate. Teleconsultation was instead deemed appropriate for the diagnosis and management of pilonidal disease. CONCLUSION: This e-consensus revealed the boundaries of telemedicine in Italy. Standardization of infrastructures, logistics, and legality remain to be better elucidated.

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-ß1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.

FISSIT (Fistula Surgery in Italy) study: A retrospective survey on the surgical management of anal fistulas in Italy over the last 15 years.

BACKGROUND: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years. METHODS: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003-2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months. RESULTS: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001). CONCLUSION: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.

Sleeve Gastrectomy Combined with Nissen Fundoplication as a Single Surgical Procedure, Is It Really Safe? A Case Report.

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has become the most common surgical procedure performed in bariatric surgery. Large hiatal hernias and Barrett's esophagus are the only contraindications recognized among experts. However, some studies have suggested that LSG may exacerbated gastroesophageal reflux disease (GERD) symptoms or induce postoperative GERD de novo. GERD and erosive esophagitis increase the risk of Barrett's esophagus. For this reason, in obese patients suffering from GERD, Roux-en-Y gastric bypass is considered the gold standard, or in the case of hiatal hernia, a laparoscopic hiatoplasty should be performed. In order to find some alternative techniques and extend the indication of LSG to obese patient with GERD symptoms, some authors have proposed a single step LSG and Nissen's fundoplication. CASE REPORT We report our experience with a male patient who after few months after a single step LSG and Nissen's fundoplication for morbid obesity and GERD, underwent emergency remnant gastrectomy and esophagojejunostomy because of gastric ischemic perforation. CONCLUSIONS We conclude that, despite being a well-tolerated and feasible surgical procedure, a single step LSG and gastric fundoplication could increase the risk of severe postoperative complications related to LSG, and we believe that, according to guidelines, gastric bypass or LSG with subsequent hiatoplasty should be preferred in obese patients with gastroesophageal reflux symptoms or hiatal hernia.

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor.

Signaling pathways have a key role in driving the uncontrolled development of familial adenomatous polyposis (FAP)- associated and sporadic desmoid tumors (DTs). The relationship between the Wnt/b-catenin signaling pathway and DTs has been extensively studied, but no reliable biomarkers able to detect their histological subtype have been identified for the accurate diagnosis. In this study we studied the differences in miRNA expression between sporadic (20 patients) and FAP-associated DTs (7 patients) using microarray confirmed by quantitative PCR (qPCR). The analysis showed 19 dysregulated miRNAs. Among them miR-133b levels were significantly lower in FAP-associated DT than in sporadic DT. Therefore, two mRNAs, associated to miR-133b and ß-catenin expression, the SIRT1 and ELAVL1were analyzed. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated DT than in sporadic DT, whereas no differences in ELAVL1 expression was observed between these two DT types. In addition, a negative correlation was observed between miR-133b and SIRT1 in FAP-associated DTs, but not in sporadic DTs. The miR-133b-SIRT1-ß-catenin axis may represent a novel mechanism underlying progression of FAP-associated DT.

Relationship between cancer tissue derived and exhaled volatile organic compound from colorectal cancer patients. Preliminary results.

New insight into the omic sciences suggests that volatile organic compounds (VOCs) contained in exhaled breath can reflect the healthy or disease state of patients, representing an attractive, promising and non-invasive method of medical investigation. This approach has recently been proposed as a new potential screening tool in colorectal cancer (CRC) patients. However, a possible correlation between the exhaled VOCs and those produced by the cancerous tissue has never been investigated. In this preliminary study, we compare the VOCs exhaled by seven patients affected by CRC with those produce by own cancer tissue and normal colonic mucosa. The VOCs contained in the exhaled breath were sampled with the ReCIVA breath sampler©, while those produced by ex-vivo human tissues weresampled by headspace solid-phase microextraction (HS-SPME) at different incubation times after surgery. In both cases, the collected VOCs were analyzed by Gas Chromatography with Mass Spectrometry (GC-MS). Benzaldehyde, benzene ethyl, benzene methyl, butanoic acid, dodecanoic acid, indole, nonanal, octanoic acid, pentanoic acid, phenol and tetradecane were the VOCs most frequently detected both in the exhaled breath and secreted by tissues. The results showed that cancer tissue and normal colonic mucosa from the same patient produced a similar VOCs pattern but with different fingerprints. In particular, the concentrations of benzaldehyde, benzene ethyl and indole were significantly different in cancer tissue respect the normal colonic mucosa. In conclusion, these preliminary data suggest the involvement of the three compounds in CRC by encouraging further investigation.

Feasibility and Safety of Laparoscopic Right Colectomy in Oldest-Old Patients with Colon Cancer: Results of the CLIMHET Study Group.

BACKGROUND: Laparoscopy for colorectal cancer treatment is widely accepted. However, there is no consensus as to whether or not laparoscopy can be considered the preferred treatment strategy in octogenarian and nonagenarian patients with colon cancer. The aim of this study was to compare operative and postoperative outcomes of laparoscopic right colectomy between oldest-old (≥80 years) and younger (<80 years) patients with colon cancer. METHODS: The study population was sampled from the CLIMHET Study Group cohort. Between January 2005 and December 2015, data were retrieved for all patients who had undergone elective laparoscopic right colectomy for colon cancer in five University Hospital centers in France (CHU of Clermont-Ferrand, Hôpital Civil of Strasbourg-IRCAD, Hôpital Henri-Mondor of Créteil, Hôpital Européen Georges Pompidou of Paris, and CHRU of Tours). RESULTS: Overall, 473 cancer patients were selected and analyzed. There were 156 oldest-old patients (median age: 84.1 years, range: 80-96) and 317 younger patients (median age: 67 years, range: 25-79). After adjusting based on propensity score on gender, obesity, American Society of Anesthesiologists score, smoking, arteriopathy, coronaropathy, comorbidity, and American Joint Committee on Cancer staging, no significant difference was found in operative and postoperative outcomes, except for time to resume a regular diet (3.6 days versus 3.0 days, P = .008) and length of hospital stay (12.1 days versus 9.1 days, P = .03), which were longer for oldest-old patients. Overall and disease-free survival rates were also equivalent between groups. CONCLUSION: These findings support that laparoscopic right colectomy can be safely performed in cancer patients aged 80 and older, and its outcomes are similar in oldest-old and younger patients.

Gene expression of fructosamine 3 kinase in patients with colorectal cancer.

OBJECTIVE: Spontaneous non-enzymatic reaction of protein amino groups with glucose and other reducing sugars, known as glycation or Maillard reaction, has long been considered irreversible and inevitably followed by slow conversion of fructosamines and advanced glycation end products. Instead, recent identification of fructosamine 3 kinase (FN3K) has unveiled that fructosamines can be physiologically repaired, so that the FN3K enzyme could be considered a new form of protein repair. METHODS: Thirty-one consecutive patients with colorectal cancer were enrolled in the study. FN3K gene expression was determined using quantitative RT-PCR. RESULTS: The mean level of FN3K gene expression was significantly lower in cancer tissue than in the corresponding normal colorectal mucosa, and FN3K gene was under-expressed most particularly in the tumours located on the left side of the colon. CONCLUSIONS: Low mRNA levels of this enzyme in colon cancer tissue with respect to normal surrounding mucosa suggests that neoplastic cells have lost a protective enzymatic system. Reduced FN3K gene expression may be important in the pathogenesis and progression of colorectal cancer.

Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations.

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with ß-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.

Fatty acid synthase hyperactivation in human colorectal cancer: relationship with tumor side and sex.

OBJECTIVE: Fatty acid synthase (FAS) is a multienzyme protein required for the conversion of acetyl coenzyme A and malonyl coenzyme A to palpitate. High levels of FAS expression have been found in many human cancers, including breast, prostate and colon. In this study, we evaluated FAS activity levels and the expression of its mRNA in normal colorectal mucosa and cancer tissue from patients operated for colorectal carcinoma. In addition, the hypothesis of a relation between FAS activity and p53 mutation status of patients was tested. METHODS: Forty-two patients were enrolled in the study. FAS activity was measured by using a radiometric assay. FAS gene expression was determined using quantitative reverse-transcription polymerase chain reaction and p53 mutations by polymerase chain reaction single-strand conformation polymorphism. RESULTS: FAS activity levels were significantly higher in cancer than in the corresponding normal mucosa. Tumors located on the left side of the colon showed higher levels of FAS activity and tumors from male patients showed higher FAS activity than tumors from females. No difference was detected in mRNA FAS levels according to tumor side and gender. Moreover, lower levels of FAS activity were detected in patients carrying the p53 mutation. CONCLUSIONS: This study suggests that biological factors including sex and gene mutation status, as well as stratification of patients with colorectal cancer into right- and left-sided subsets, may be important in patient selection for targeted therapies and for the subsequent assessment of objective therapeutic responses.