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Background: Haemorrhoidal disease (HD) is a benign condition affecting a considerable part of adult population. HD can be considered a social and economic burden with high impact on patients’ lifestyle. Several new techniques and devices have been proposed for HD treatment; however, preoperative assessment is essential and the use of classification system is recommended. Methods:: In the last two decades many studies described the preoperative assessment and several attempts of classification for HD. This review focuses on the most relevant studies found in literature where classification systems and clinical evaluation with differential diagnosis have been evaluated. Results: The knowledge of classification systems and differential diagnosis for HD has been shown to play a central role in the clinical assessment and the best treatment choice. Although there are new challenging techniques and devices for HD treatment, a preoperative assessment is always mandatory. Conclusion: Preoperative clinical evaluation is essential for HD patient treatment and outcome. Classification systems are useful for the therapeutic choice and researches on new medical or surgical treatments. In fact, the international guidelines advise several therapeutic options depending on the severity of the HD.

Background The efficacy of sacral nerve stimulation (SNS) on patients with chronic refractory slow-transit constipation is controversial and its mechanism of action on gastrointestinal motility and transit is not fully understood. The aim of this study was to document the effects of temporary SNS on the gastrointestinal and biliary tract motility and on gastrointestinal transit in patients with refractory slow-transit constipation. Methods This was a prospective interventional study. Patients with slow-transit chronic constipation, unresponsive to any conservative treatment, were enrolled between January 2013 and December 2018. Patients’ quality of life [patient assessment of constipation quality of life (PAC-QOL) questionnaire], constipation scores (Cleveland Clinic Constipation Score) colonic transit time (CTT), orocecal transit time (OCTT), gastric and gallbladder kinetics, together with the assessment of the autonomic nerve function were evaluated before and during temporary SNS. Results 14 patients (12 females, median age 38 years, range 24–42 years) had temporary SNS. The Cleveland Clinic Constipation Score did not change compared to baseline (23 ± 3 vs 21.4; p = 070). The PAC-QOL did not improve significantly during the stimulation period. Gallbladder/stomach motility (half-emptying time) did not change significantly before and after SNS. OCTT was delayed at baseline, as compared to standard internal normal values, and did not change during SNS. CTT did not improve significantly, although in two patients it decreased substantially from 97 to 53 h, and from 100 to 65 h. Conclusions Temporary SNS did not have any effect on upper/lower gastrointestinal motility and transit in patients with severe constipation.

In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer.Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models.Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea.It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.

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.

Simple Summary Emerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process. Abstract 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-β1 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.

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.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).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.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.

Background: Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. Aims: To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. Methods: Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. Results: The pooled sensitivity and specificity of FIT at 10µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI]=0.894-0.936) and 0.783 (CI=0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI=0.781-0.881) and the specificity was 0.803 (CI=0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. Conclusions: In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.

Trop-2 is a type I transmembrane glycoprotein, which is overexpressed in the majority of carcinomas, where it drives tumor cell proliferation. In its mature, glycosylated/functionally-competent form, Trop-2 associates with worse prognosis. A global quest was conducted for identifying decisive drivers of cancer metastasis. Cancer cell spheroids, wound healing and cell aggregation assays were utilized to assess cell-cell adhesion capacity. Immunofluorescence confocal microscopy and flow cytometry analysis were utilized to quantify expression of target signaling proteins, IHC analysis quantified the expression of target molecules in primary tumors and metastases. Pre-clinical models of orthotopic growth of colon cancer and metastatic diffusion to the liver were utilized. Xenotransplant transcriptome profiling analyzed transcription of EMT-related determinants. This led us to identify Trop-2 as a unique upregulated gene in colon cancer metastasis. Trop-2 was here shown to bind highly-expressed E-cadherin at the cell membrane. Trop-2 binding released E-cadherin from the cytoskeleton, inhibited cell-cell adhesion functions and activated signaling through β-catenin. This occurred in the absence of transcriptional downregulation of the CDH1 gene by EMT-associated transcription factors. The Trop-2/E-cadherin/β-catenin program was shown to lead to anti-apoptotic signaling, increased cell migration and enhanced cancer cell survival. In an orthotopic model of colon cancer, Trop-2 caused metastatic diffusion to the liver. The Trop-2-led E-cadherin-inactivation metastasis program was then found to induce metastatic relapse and shorter overall survival of colon cancer patients. Corresponding impact was indicated on breast, colon, ovary, uterus, stomach cancer metastatic diffusion, for broad impact on metastatic diffusion in human cancer. Acknowledgments:Support was provided by grants of Italian Ministry of Development (MI01_00424) and of University and Research (SCN_00558). M.T. was supported by the Programma Per Giovani Ricercatori “Rita Levi Montalcini” (Grant PGR12I7N1Z). Citation Format: Saverio Alberti, Emanuela Guerra, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, donato F. Altomare, Raffaella Depalo, Marco Trerotola. Trop-2 inactivates E-cadherin for metastatic diffusion in the absence of EMT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2851.

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.

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. 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®). 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). The results of this pilot study suggest a potential role of local spray application of Glubran®2 in reducing post-procedural bleeding.

Patient: Male, 40-year-old Final Diagnosis: Gastric perforation Symptoms: Abdominal pain Medication:— Clinical Procedure: Sleeve gastrectomy Nissen fundoplication Specialty: Surgery Objective: Unusual clinical course 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.

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 β-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-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated DT.

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.

Obstructed defecation syndrome (ODS), most commonly found in females, can be treated by a transanal or abdominal approach with good success rate. Nevertheless, patients may experience de novo or persisting pelvic floor dysfunctions after surgery. The aim of this study was to compare the functional outcome of stapled transanal rectal resection (STARR) and ventral rectopexy (VRP) in a series of ODS patients. Forty-nine female patients who had surgery for ODS between 2006 and 2016 were retrospectively evaluated: 28 (median age 60 years, IQR 54–69 years) had VRP and 21 (median age 58 years, IQR 51–66 years) had STARR. ODS was scored with the ODS score while the overall pelvic floor function was assessed with the three axial perineal evaluation (TAPE) score. Quality-of-life was evaluated by the patient assessment of constipation quality-of-life (PAC-Qol) questionnaire administered preoperatively and after 1 year of follow-up. The preoperative median ODS score and TAPE score were comparable in both groups. After a median follow-up of 12 months (range 12–18 months), the median ODS score was 12 (range 10–20) in the STARR group and 9 (range 3–15) in the VRP one (p = 0.02), while the median TAPE score was 70.5 (IQR 60.6–77.3) in the former and 76.8 (IQR 70.2–89.7) in the latter (p = 0.01). Postoperatively the physical domain of the PAC-QoL score had a median value of 2.74 (IQR 1.7–3.75) in the STARR group compared to 1.5 (IQR 1–2.5) in the VRP group (p = 0.03). No major complications were recorded in either group. VRP and STARR can improve defecation in patients with ODS with minimal complications, but the overall pelvic wellness evaluated by the TAPE score improves significantly only after VRP, suggesting a better performance of VRP than STARR when overall pelvic floor function is concerned.

e15576 Background: Metastatic diffusion is the biggest hurdle for colon cancer (CRC) cure and the identification of decisive drivers of CRC metastasis is an urgent need in CRC care. Methods: The expression of target molecules in primary tumors and metastases was systematically assessed by DNA array and IHC analysis. Cell-cell adhesion capacity was quantified in 2D cell cultures and in HCT116 CRC cell spheroids. Pro-metastatic impact of wtTrop-2 and activated, tail-less Trop-2 (Δcyto) was assessed in vivo in orthotopic diffusion models of KM12SM CRC cells. Primary CRC and metastasis transcriptomes were analyzed for differential induction of EMT determinants. Kaplan–Meier plots were used to illustrate survival and metastatic relapse in independent case series of CRC patients. Results: Trop-2 was identified as uniquely upregulated in CRC models by transcriptome analysis. wtTrop-2 and ΔcytoTrop-2 were shown to induce cell migration, wound-healing and resistance to apoptosis induction . wtTrop-2 increased the metastatic capacity of KM12SM cells, raising metastasis diffusion from 45% for control cells to 90% for wtTrop-2 transfectants. The constitutively-active ΔcytoTrop-2 further boosted metastatic spreading, with metastatic livers reaching up to four times their normal size. Constitutive high expression of E-cadherin was revealed in cancer metastases. No evidence was obtained for transcriptional down-regulation of epithelial differentiation biomarkers. No induction of EMT transcription factors was observed in Trop-2-activated cells. Trop-2 tightly bound E-cadherin and caused its release from the cytoskeleton, for loss of cell-cell adhesion and activation of β-catenin. The Trop-2/E-cadherin/β-catenin-driven pro-metastatic program was recapitulated in CRC patients and was shown to impact on CRC metastatic relapse and overall patient survival. Conclusions: We identify Trop-2-driven functional inactivation of E-cadherin as a key driver of metastatic diffusion in CRC. These findings may pave the way for novel multi-marker personalized diagnostics and anti-cancer therapies. [Table: see text]

// Aldo Cavallini 1, * , Maria Teresa Rotelli 2, * , Catia Lippolis 1 , Domenico Piscitelli 3 , Rosa Digennaro 2 , Claudia Covelli 3 , Nicola Carella 1 , Matteo Accetturo 4 and Donato Francesco Altomare 2 1 Laboratory of Cellular and Molecular Biology, National Institute for Digestive Diseases, IRCCS “Saverio de Bellis”, Castellana Grotte (BA), Italy 2 General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 3 Section of Pathology, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy 4 Nephrology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari “Aldo Moro”, Bari, Italy * These authors contributed equally to this work Correspondence to: Aldo Cavallini, email: cavaldo@libero.it Keywords: desmoid tumor, microRNA, CTNNB1 mutations, tetraspanin3 (TSPAN3) mRNA, serpin family A member 3 (SERPINA3) mRNA Received: November 16, 2016 Accepted: February 22, 2017 Published: March 19, 2017 ABSTRACT 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 β-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.

Recto-vaginal (RVF) and recto-urethral (RUF) fistulas are infrequent but disabling conditions that severely affect patients’ quality of life. Considering the high recurrence rate after conservative approaches, the best surgical treatment is still challenging. The aim of this study was to evaluate the outcome of graciloplasty to treat patients with complex RVF or RUF, and to investigate its effect on the quality of life. Fourteen patients with RVF and RUF who underwent graciloplasty between 2003 and 2017 were retrospectively enrolled. The main outcome was the healing rate of fistulas. Postoperative patients satisfaction was evaluated administering the Clinical Patient Grading Assessment Scale (CPGAS), SF-36 questionnaires and Changes in Sexual Functioning (CSF) questionnaires. The Wexner score was calculated in case of preoperative faecal incontinence. RVF and RUF were iatrogenic in 11 patients and due to Crohn’s disease in 3 cases. After 1 year of follow-up (IQR 10–14 months), the success rate of the procedure was 78%. Out of three patients with RVF due to Crohn’s disease, two healed after the procedure. Six months after surgery, all eight SF-36 domains significantly improved except for “body pain”; CSF score significantly increased from 35.5 (IQR 31–38.7) to 44 (IQR 37.7–48.5); CPGAS score improved from a median value of 0 (IQR 0–0) to 4 (IQR 3.2–4). The Wexner score was calculated only in 5 patients with preoperative faecal incontinence and it significantly decreased from a median value of 12 (IQR 11–14) to 5 (IQR 4–5). Graciloplasty could be considered as a first option treatment for complex or recurrent RVF and RUF. It shows a good healing rate even in case of unfavourable factors like Crohn’s disease.

Background This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high‐resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Methods Twenty‐nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face‐to‐face and three remote meetings to derive consensus between 2014 and 2018. Key recommendations The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. Conclusions and Inferences This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much‐needed standardization to these techniques., This document summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance of anorectal function testing and introduces a consensus classification for disorders of anorectal function based on objective, physiological measurement.

Highlights • Optimal timing to treat esophago-gastric necrosis due to caustic ingestion. • Proposal of three steps approach to manage esophago-gastric necrosis. • Use of Cyanoacrylate glue to reinforce anastomosis. • Vacuum Assisted Closure for damage control after surgery., Introduction The surgical treatment of a complete gastric necrosis due to caustic ingestion is extremely challenging and life threatening. In this emergency scenario, a first-time reconstruction of the gastrointestinal tract is often dangerous for the patient because of the high risk of infections and anastomosis leakage. Literature lacks of clear indications for the management of this condition. Presentation of case Male patient with history of major depression disorder was admitted to our Emergency Unit after the ingestion of muriatic acid. CT scan showed massive pneumo-peritoneum with esophago-gastric thickening. Free fluids in the abdominal cavity were detected. Intraoperative finding was a complete necrosis of the stomach and corrosion of the lower esophagus. Discussion In this case report we proposed a first approach with the drainage and lavage of the abdomen cavity. Then, an esophago-jejunum anastomosis reinforced by Cyanoacrylate glue was performed and a damage control with VAC therapy (Vacuum Assisted Closure) was carried out. Conclusion Cyanoacrylate glue could be considered useful and efficient in the reinforcement of anastomosis even in emergency surgical procedures. Damage control using VAC allows to keep a good control of the surgery performed.

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.

Cholecystectomy for gallstone is one of the most frequently performed abdominal operations because of the large diffusion of the gallstone disease in the western population and for the adoption in the last 25 years of the laparoscopic cholecystectomy technique instead of the open surgery [1]. In fact, the minimal invasiveness of the laparoscopic procedure has extended the indication for gallbladder removal even if the international guidelines discourage the operation in cases of asymptomatic gallstones accidentally discovered during an abdominal ultrasound.

Intestinal stoma (from the Greek language στομα = mouth) formation (ostomy surgery) is a surgical procedure intended to divert the intestinal content outside the body through the abdomen. Due to its profound impact on the patients’ emotional status and on their quality of life, a detailed preoperative counselling is mandatory, while the adhesion to strict technical rules is fundamental to prevent the frequent stoma complications.

Surgery for the treatment of anorectal diseases can result in functional disorders of defecation, both anal incontinence and obstructed defecation. In this chapter we have reviewed the most common operations performed on the anus and rectum for benign or malignant diseases and have listed the diagnostic tools currently used for their evaluation. Finally, the possible treatments available today have been reviewed.

The most frequent diseases involving the small bowel and requiring surgery are Crohn’s disease and postoperative or post inflammatory adhesion. Less frequently small bowel resection is performed because of ischemia for mesenteric artery thrombosis or embolism and for neoplastic diseases arising in the small bowel (rare) or compressing or infiltrating the small bowel from outside (desmoid tumors, sarcomas, lymphomas, etc.). Furthermore, the small bowel is often interested by penetrating wounds (stab wounds or gunshot wounds) or can be strangulated in inguinal hernia, ventral hernia, or volvulus. Another rare small bowel disease requiring surgery is intussusception often associated to pedunculated polyps.

Total or partial resection of the stomach is a major surgery performed mainly for complications of peptic ulcers (bleeding, stricture, perforation) or for gastric cancer. Other less frequent indications are benign tumors and severe gastroparesis. Gastric surgery for obesity will be treated in a separate chapter.

105 Background: Tumor metastasis is the main cause of death of colon cancer patients and the biggest hurdle for cancer cure. We set to identify decisive drivers and of pivotal therapy targets for colon cancer metastasis. Methods: IHC analysis quantified the expression of target molecules in primary tumors and metastases. Cell-cell adhesion capacity was assessed in vitro and in HCT116 colon cancer cell spheroids. Pre-clinical models of orthotopic growth of KM12SM colon cancer cells and metastatic diffusion to the liver were utilized to assess metastatic spreading force of wtTrop-2 and of the constitutively-active, tail-less form of Trop-2 (Δcyto). Xenotransplant and metastasis transcriptomes were analyzed for differential induction of EMT determinants. Kaplan–Meier plots were used to illustrate survival and metastatic relapse in independent case series of colon cancer patients. Results: wtTrop-2 was shown to induce wound-healing. ΔcytoTrop-2 further increased cell migration ability. Both wtTrop-2 and ΔcytoTrop-2 induced resistance to apoptosis in vitro and in vivo. wtTrop-2 strikingly increased the metastatic capacity of KM12SM cells, raising metastasis rates from 45% for control cells to 90% for wtTrop-2 transfectants. The constitutively-active ΔcytoTrop-2 further boosted metastatic spreading, with metastatic livers reaching up to four times their normal size. Cancer metastases revealed high levels of E-cadherin, in the absence of transcriptional down-regulation. EMT transcription factors were largely missing from Trop-2-activated cells. Rather, binding to Trop-2 was shown to cause the release of E-cadherin from the cytoskeleton, loss of cell-cell adhesion and activation of β-catenin. This global, Trop-2/E-cadherin/β-catenin-driven pro-metastatic program was recapitulated in colon cancer patients and was shown to impact on colon cancer metastatic relapse and overall patient survival. Conclusions: We identify Trop-2-driven functional inactivation of E-cadherin as a widespread driver of metastatic diffusion in colon cancer, opening novel avenues for personalized diagnostic procedures and anti-cancer therapies. [Table: see text]

Patient: Female, 60-year-old Final Diagnosis: Pneumatosis intestinalis Symptoms: Abdominal pain Medication:— Clinical Procedure: — Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Hepatic portal venous gas (HPVG) associated with pneumatosis intestinalis (PI) can be indicative of several diseases, including inflammatory bowel disease (IBD), infective and obstructive gastrointestinal conditions, and also potentially life-threatening situations such as mesenteric ischemia. Case Report: A 60-year-old female patient came to our attention with evidence at computed tomography (CT) scan of gas in the portal vein and bowel walls with no sign of ischemia. General tenderness of the abdomen with absence of bowel sounds was detected at the physical examination. An exploratory laparotomy was performed with evidence of mesenteric ischemia. Conclusions: Emergency surgery should be indicated when CT signs of PI and HPVG occur along with a clinical situation strongly suggestive of bowel ischemia, even with no radiological sign of this critical condition.

Aim Epidemiological studies have shown that the incidence and mortality rates of colorectal cancer (CRC) vary over 10-fold worldwide where within Westernized societies lower rates are observed amongst populations living within the Mediterranean basin, suggesting a significant influence of environment and dietary style in CRC carcinogenesis. Interpretation of the data concerning the benefits of mediterranean (MD) diet is difficult in vivo because of the variability of alimentary regimens used, the differing compliance with dietary supplementation and because of the non-uniform duration of patient cohort observation. Therefore, the aim of this review is to evaluate the in-vitro effects on colorectal cancer cell lines. Methods the literature concerning the in-vitro effects of 4 of the principal components symbolizing the MD such as olive oil (polyphenol), red chili (capsaicin), tomato (lycopene) and red grapes (resveratrol) have been systematically reviewed. Results Several studies have demonstrated that polyphenols form olive oil, lycopene, resveratrol and capsaicin have multiple anticancer properties affecting several metabolic pathways involved in cancerogenesis, apoptosis, and metastasis in CRC cell lines. Conclusion This review summarizes some of the most recent data potentially supportive of the use of MD in CRC chemoprevention, analyzing the in vitro effects of individual components of the MD on CRC cell development, progression, metastasis and apoptosis.

Several comments immediately following the British vote for Brexit focused on the negative effects both in general terms and in individual sectors, such as that of scientific research. The most feared consequence is the isolation and loss of funding for researchers in community projects. British commentators were later joined by many other European and non-European countries who have interpreted Brexit as a manifestation of impatience with Europe, its constraint and lack of flexibility, topped by an all-English presumption, that they can do better by themselves. This article is protected by copyright. All rights reserved.

Aim: Abnormalities of one pelvic floor compartment are usually associated with anomalies in the other compartments. Therapies which specifically address one clinical problem may potentially adversely affect other pelvic floor activities. A new comprehensive holistic scoring system defining global pelvic function is presented. Method: A novel scoring system with a software program is presented expressing faecal, urinary and gynaecological functions as a geometric polygon based on symptom-specific questionnaires [the three axial pelvic evaluation (TAPE) score] where differences in overall geometric area vary from normal. After validation in healthy volunteers, its clinical performance was tested on patients with obstructed defaecation, genital prolapse and urinary/faecal incontinence treated by the stapled transanal rectal resection (STARR) procedure, colpo-hysterectomy and sacral nerve modulation, respectively. The TAPE score was correlated with the Pelvic Floor Impact Questionnaire 7 quality of life score. Results: There was good inter-observer variation and internal consistency between two observers recording the TAPE score in normal volunteers. In the STARR patients, constipation improved but the TAPE score was unchanged because of deterioration in other pelvic floor functions leading to an unchanged overall postoperative recorded quality of life. Conversely, incontinent patients treated with sacral nerve stimulation improved their function showing concomitant improvements in TAPE scores and quality of life indices. Similar correlative improvements were noted in patients undergoing hysterectomy for genital prolapse. Conclusion: The TAPE score defines the impact of symptom-specific treatments on the pelvic floor and may provide an opportunity for comparison of clinical data between units and in clinical trials of specific medical and surgical pelvic floor management. (Less)

Patients with gallstones are often affected by alimentary disorders contributing to the onset of gallstones disease. Cholecystectomy can have nutritional and metabolic consequences in the short-term (diarrhea, abdominal pain and bloating) and in the long-term (increased Body Mass Index with metabolic syndrome, gastritis, liposoluble vitamin deficiency). Pathogenic mechanisms behind these disturbances are reviewed and the need for an early post-operative nutritional intervention based on low-lipid, high-fibers diet, is highlighted.

AIM Sacral nerve stimulation is an effective treatment for urinary and faecal incontinence even though its mechanism of action is uncertain. Central nervous system involvement by 'setting-up' neurological mechanisms appointed to control pelvic function has been hypothesized. The study aimed to evaluate whether the effects of long-term sacral nerve stimulation are memorized and therefore maintained after switching off the stimulator. METHOD Patients having sacral nerve stimulation for faecal and/or urinary incontinence for at least 1 year had the stimulator turned off and the results monitored. Data recorded with the stimulator off were compared with post-implant data. If symptoms recurred the stimulator was switched back on. Nineteen patients entered the study. Fourteen had faecal and/or urinary incontinence and five had faecal incontinence alone. The symptoms were assessed by means of a bowel function diary and dedicated questionnaire. RESULTS In 10 patients symptoms recurred at different intervals after a median off period of 3.4 months with a probability of symptom relapse of 55%. The Fecal Incontinence Quality of Life (FIQL) score did not show any significant difference in nine patients with the stimulator off for at least 1 year. No factors predictive of symptom recurrence were identified although an idiopathic aetiology, severity of disease and urinary incontinence had higher hazard ratios. During the off period, none of the scores and episodes of incontinence showed significant changes compared with the on period. CONCLUSION The effects of sacral nerve stimulation on faecal and urinary incontinence were maintained in about half of patients after switching the stimulator off, but in some symptoms returned after different periods of time. The data shed new light on possible effects of sacral nerve stimulation on brain neuroplasticity in the control of continence.

Dear Editor: Endometriosis largely affects women, particularly during the fertile age, causing dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility in about 30 % of patients [1]. Its occurrence is estimated to be about 10 % in women in reproductive age, while postmenopausal endometriosis is much less frequent, affecting up to 2–4 % of women, usually in patients with a history of premenopausal disease. Pelvic deep endometriosis infiltrating the rectum and surrounding tissues usually causes severe symptoms, especially pain and obstruction, and its treatment is challenging, because of risk of injury of the pelvic organs and because of the high recurrence rate. Furthermore, even if endometriosis is a benign condition, it has the potential for malignant transformation [2], which occurs in 0.7–1 %, particularly in the ovaries [3]. The endometrial heterotopic tissue is functionally capable of responding to exogenous, endogenous, or local hormonal stimuli, and this estrogen dependence is considered central to its development and progression. For this reason, endometriosis is widely viewed as a disease of the premenopausal age, which normally regresses after menopause because of the lower production of estrogens, even if rare occurrence of endometriosis has been reported in postmenopausal period. In that case, the adipose tissue is supposed to become the main site of endogenous estrogen production even if unopposed hormonal replacement therapy is usually prescribed. However, the onset of deep endometriosis in postmenopausal women submitted to hysterectomy and bilateral oophorectomy for fibromatosis and without hormonal therapy is very rare and represents a conundrum with difficult interpretation. A 54-year-old woman was admitted to our hospital with severe pelvic and anal pain, constipation, and oliguria. Her body mass index was 29. Her personal history included menarche at age 12, with irregular menstrual cycles and dysmenorrhea. She had been pregnant three times, with two spontaneous abortions and one successful pregnancy with cesarean delivery. At the age of 43, she underwent laparotomic hysterectomy and bilateral salpingo-oophorectomy for leiomyomatosis of the uterus. Hormone replacement therapy was not prescribed after surgery. Histologic examination of the resected specimen showed multiple intramural leiomyoma of the uterus, minute borderline cystadenoma, and cyst of the right ovary. At the time of hospitalization, she denied any history of urinary symptoms, and rectal digital examination revealed a palpable, painful, hard, and fixed mass of the pelvis infiltrating the rectal wall. The serum concentrations of carbohydrate antigen 125 (CA 125) and carbohydrate antigen 15.3 (CA 15.3) were 134.4 and 44 .3 U/ml , respec t ive ly. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels were normal. Endoscopic examination revealed the presence of a pelvic mass compressing the walls of the rectum without mucosa infiltration at 8 cm from the anal verge and a large (>5 cm) villous polypoid lesion of the posterior wall of the rectum. Histology on the rectal biopsies from the polyp documented a villous V. Andriola :M. Battaglia : P. Ditonno :M. G. Fiore :M. De Fazio : R. Memeo :D. F. Altomare Department of Emergency and Organ Transplantation, University BAldo Moro^ of Bari, Bari, Italy

The management of haemorrhoids has evolved rapidly during the past few decades. Several new treatments have been proposed with the aim of reducing patients' postoperative pain, time to return to normal life, risk of early and late complications, and recurrence rate. Although conservative treatment based on dietary and lifestyle changes can help the majority of patients, and rubber band ligation and phlebotonic drugs can effectively treat grade I and II haemorrhoids, surgery is required for the most advanced stages. Milligan-Morgan haemorrhoidectomy is considered to be the gold-standard approach for grade IV haemorrhoids. An increasing number of minimally invasive treatment options, including mucopexy with or without mucosal resection and haemorrhoid artery ligation, have now been proposed for the management of grade III haemorrhoids. These approaches aim to correct the underlying pathophysiological mechanisms involved in the aetiology of haemorrhoids. An increased risk of recurrence is the price to pay for these minimally invasive and less painful treatments, but the sparing of the sensitive anoderm and a rapid return to normal life without pain are greatly appreciated by patients. An algorithm for the management of haemorrhoids using evidence-based medicine is also presented here.