Simona Giuratrabocchetta

The effects of sacral nerve stimulation on continence are temporarily maintained after turning the stimulator off

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.

MicroRNA: future perspectives in colorectal cancer.

MicroRNAs are short 18–22 nucleotide non-coding RNA molecules involved in regulation of gene expression through post-transcriptional processing. Their genetic sequences have been preserved unmodified in phylogenesis and among distantly related organisms, suggesting an ancestral role in the control and regulation mechanisms of life on the planet. They were identified in 2001 by Victor Ambros [1] who found that the lin-4 gene, involved in the development of a nematode (Caernorhabditis elegans), did not code for a protein but for a small 22-nucleotide RNA fragment able to inhibit lin-14 expression by interacting with the non-coding 3¢UTR region of lin-14. The paramount importance of this research in understanding human physiology and disease resulted in the award of the Nobel Prize to AndrewFire and Craig Mello in 2006. Since then, many new microRNAs have been identified leading to the creation of microRNA databases (miRBase, miR-liB), in which the genetic sequences and functions are recorded. Currently about 940 microRNAs have been identified, but the relationship with a specific biomolecular process is unknown for most. MicroRNAs can bind the non-coding 3¢UTR region of their mRNA targets, inhibiting the mRNA translation and therefore affecting gene expression. Their stability in the evolution of the species suggests an important role in biological processes, such as cell growth and differentiation, proliferation and apoptosis. They have been isolated from stool, sputum, serum and plasma, allowing a wide range of applications in clinical research as the molecule seems to be chemically stable and resistant to RNase present in stool and serum. Studies of the evolution of cancer have revealed how altered microRNA expression can be linked to disease. A hypothesis of their disease-specific pattern as potential diagnostic biomarkers has created great enthusiasm. MicroRNA expression is deregulated in cancer cells, affecting gene activity (deletion, amplification, silencing) and inducing post-transcriptional changes. Altered microRNA expression has been documented in several cancers, including diffuse large B-cell lymphoma (miR155, miR210, miR21), prostate cancer (miR141), breast cancer (miR195 and let-7a) and non-small-cell lung cancer (miR25, miR223, miR21, miR17-3p, miR155). Intensive research of microRNA expression and colorectal cancer (CRC) is increasing. Volgenstein’s hypothesis is well accepted, suggesting the role of specific gene mutations (APC, K-ras, DCC, P53) and pathway deregulation (Wnt, EGFR, TGF-b, p53) as the main mechanisms involved in adenoma cancer progression. Interestingly, recent studies have demonstrated the role of some microRNAs in the regulation of these pathways (Fig. 1). It has been proved that microRNAs 135a and 135b are involved in the Wnt pathway, through the regulation of oncosuppressor APC gene expression, which controls cell proliferation and the mutations of which are considered the first step for the abnormal proliferation of colonic cells. An increased expression of these microRNAs causes decreased APC protein levels, allowing bcatenin to move into the nucleus and activate the transcription of genes involved in cell-cycle regulation. Two other microRNAs, miR-143 and miR-145, are under-expressed in several types of cancer including CRC. Their role in intestinal carcinogenesis has not yet been clarified, but probably miR-145 is involved in c-myc gene expression and miR-143 in the EGFR pathway regulation, affecting K-ras gene expression. Reduced levels of the miR34a–c family which targets the p53 gene have also been demonstrated. The final effect of this downregulation is the loss of apoptosis, through an increased expression of Bcl-2, encouraging increased cell survival and proliferation. Identification of specific patterns of microRNAs in CRC is a very hot topic in basic research. At the moment decreased expression of miR133b, miR14 and miR145 and a higher expression of miR31, miR183, miR17-5, miR92, miR18a, miR20a, miR96, miR135b and miR183 were demonstrated in cancer specimens compared with normal colonic mucosa. Altered mRNA expression was also looked for in the stools of CRC patients, where it could represent an optimal screening tool. Colonic cancer cells exfoliate in greater quantity and their nucleic acid

Safety and short‐term effectiveness of EEA stapler vs PPH stapler in the treatment of degree III haemorrhoids: prospective randomized controlled trial

Aim  Stapled haemorrhoidopexy has gained wide acceptance due to less postoperative pain although postoperative bleeding and prolapse recurrence are among the major drawbacks of this technique compared with the standard Milligan–Morgan hemorrhoidectomy. The aim was to investigate a new stapler device designed to overcome these side effects.

The Three Axial Perineal Evaluation (TAPE) score: a new scoring system for comprehensive evaluation of pelvic floor function.

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.

Sacral Nerve Modulation for Fecal Incontinence

Sacral nerve stimulation is an innovative, mininvasive approach to fecal incontinence and other pelvic floor dysfunctions based on the delivery of electrical stimuli to the pelvic nerves through an electrode percutaneously positioned through the sacral foramen (usually S3) and connected to an implantable pulse generator. This technique has the unique advantages to affect continence without performing operations on the anal sphincter and to have the possibility to pretesting the outcome of the definitive implant with a low-cost temporary stimulation. Its reliability and effectiveness is nowadays recognized by the FDA [1], by the NICE [2], and by the main Coloproctological scientific societies (ASCRS, ESCP, ICS) and systematic reviews [3].

TriAxial perineal evaluation score: the male version

All authors contributed to this work: A. Resegotti proposed the technique and operated on the patients. A. Resegotti and S. Silvestri designed the study. A. Resegotti, S. Silvestri and A. Falcone wrote the manuscript. A. Resegotti, A. Franchello and S. Silvestri supervised the paper. The other authors collected data and reviewed literature articles. All authors discussed technique and implications and commented on the manuscript at all stages.

The Role of Surgery in Chronic Constipation: When and Why

Constipation is the most frequent bowel dysfunction with paramount affects on people’s quality of life and mental wellness; it has been estimated that about 30% of people in western countries are afflicted by constipation (1) with heavy aftermath on the health national system. Constipation can be a primary disorder or secondary to neurological, pharmacological, depression, endocrine diseases or child abuse (2). Primary constipation is commonly distinguished in slow transit type, outlet obstruction or both, according to “Rome III Criteria” (3). Females of any age are more frequently affected by both these types of constipation. The incidence of true slow transit constipation in presence of a normal colon was overestimated in the past, whilst an increasing number of outlet obstruction constipation cases are now identified after the availability of new diagnostic procedures. Clinical work-up in patients with constipation should focus on the exclusion of organic or secondary causes of constipation by colonoscopy (or barium enema) and accurate anamnesis, followed by more specific functional investigations (colonic transit study by radiopaque markers for slow transit constipation, and dynamic defecography for outlet obstruction). Complementary investigations are anorectal manovolumetry (to exclude Hirschsprung’s disease and rectal hyposensitivity) and some autonomic tests to identify patients with autonomic neuropathy which will probably do not benefit from surgery (4). Another clue point in this work-up is the assessment of the severity of the disease using dedicated scoring systems [Wexner-Agachan score (5), KESS score (6), Altomare ODS score (7), PAC-SYM score (8)] and the evaluation of effects of the disease on patient’s quality of life [PAC QoL (9) and CRQoL (10)]. These evaluation have recently been introduced not only in clinical research but also in the clinical decision making process. Although constipation is mainly a medical problem, there are several cases which could benefit from surgery. A surgical approach to slow transit constipation dates back to the early Victorian age in England (11) where Arbuthnot Lane first performed successfully a total colectomy for constipation getting fame and honors (for this he was nominated Sir by her majesty the Queen Victoria). However this aggressive approach fall into disgrace when he’s theory of fecal autointoxication was revealed unsubstantiated and surgery for constipation was abandoned for more than 60 years. Nowadays colectomy and ileorectal anastomosis for treating slow transit constipation is considered the last option in a very selected group of patients when any other kind of treatments has failed and when the patient’s quality of life is severely compromised. For this type of constipation, beside polyethylene glycol based laxatives (12, 13, 14), an increasing number of new drugs have been experimented and are currently under trial, targeting different mechanisms of action like chloride-channel

The Altemeier’s Procedure for External Rectal Prolapse

During the 19th and 20th centuries, different perineal approaches were proposed for the treatment of external rectal prolapse, and despite the high recurrence rate of the prolapse they were preferred to the abdominal approach. In recent decades, the improvement in general anesthesia and perioperative care, and the widespread use of laparoscopic techniques, have enabled the abdominal approach to become more common, as it is believed to carry a lower recurrence rate and probably better functional results.

Functional Assessment of Anorectal Function

Disorders of the posterior compartment of the pelvic floor are essentially represented by disorders of defecation, fecal incontinence, and constipation. Their functional assessment includes the evaluation of their severity, their impact on quality of life (QoL), and their etiology, by means of medical history, and clinical and instrumental examinations of the perineum and the anorectum.