Corrado R. Asteria

Treatment of perianal fistulas in Crohn's disease by local injection of antibody to TNF-α accounts for a favourable clinical response in selected cases: A pilot study

Objective. Intravenously administered infliximab, a monoclonal antibody directed against tumor necrosis factor-α, has been proven to be efficacious in the treatment of fistulas in patients with Crohns disease. It has recently been suggested that local injections of infliximab might be beneficial as well. The aim of this study was to assess whether infliximab could play an effective role in the local treatment of perianal fistulas in Crohns disease. Material and methods. Local infliximab injections were administered to 11 patients suffering from Crohns disease complicated by perianal disease. Eligible subjects included Crohns disease patients with single or multiple draining fistulas, regardless of status of luminal disease at baseline. Patients, however, were excluded from the study if they had perianal or rectal complications, such as abscesses or proctitis or if they had previously been treated with infliximab. Twenty-milligram doses of infliximab were injected along the fistula tract and around both orifices at baseline and then every 4 weeks for up to 16 weeks or until complete cessation of drainage. No further doses were administered to patients who did not respond after three injections. Efficacy was measured in terms of response (a reduction in fistula drainage of 50% or more) and remission (complete cessation of fistula drainage for at least 4 weeks). Time to loss of response and health-related quality of life were also evaluated. Results. Overall, 8/11 patients (72.7%) responded to the therapy and 4/11 (36.4%) reached remission, whereas 3/11 patients (27.2%) showed no response. Response or remission was very much dependent on the location of the fistulas, and time to loss of response was generally longer for patients who reached remission compared to patients in response. Changes in health-related quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), also reflected response or remission, with more marked improvements associated with remission. After a mean 10.5 months’ follow-up (range 7–18 months), 6/11 patients (54.5%) are in response and 4/11 patients (36.4%) are in remission. No adverse events have been observed in this cohort of patients. Conclusions. Local injections of infliximab along the fistula tract seem to be an effective and safe treatment of perianal fistulas in Crohns disease. However, further controlled clinical investigations are warranted.

Anastomotic leaks after anterior resection for mid and low rectal cancer: survey of the Italian Society of Colorectal Surgery

Background The aim of the survey was to assess the incidence of anastomotic leaks (AL) and to identify risk factors predicting incidence and gravity of AL after low anterior resection (LAR) for rectal cancer performed by colorectal surgeons of the Italian Society of Colorectal Surgery (SICCR)Methods Information about patients with rectal cancers less than 12 cm from the anal verge who underwent LAR during 2005 was collected retrospectively. AL was classified as grade I to IV according to gravity. Fifteen clinical variables were examined by univariate and multivariate analyses. Further analysis was conducted on patients with AL to identify factors correlated with gravityResults There were 520 patients representing 64% of LAR for rectal cancer performed by SICCR members. The overall rate of AL was 15.2%. Mortality was 2.7% including 0.6% from AL. The incidence of AL was correlated with higher age ( p <0.05), lower (<20 per year) centre case volume ( p <0.05), obesity ( p <0.05), malnutrition ( p <0.01) and intraoperative contamination ( p <0.05), and was lower in patients with a colonic J-pouch reservoir ( p <0.05). In the multivariate analysis age, malnutrition and intraoperative contamination were independent predictors. The only predictor of severe (grade III/IV) AL was alcohol/smoking habits ( p <0.05) while the absence of a diverting stoma was borderline significant ( p <0.07)Conclusion Our retrospective survey identified several risk factors for AL. This survey was a necessary step to construct prospective interventional studies and to establish benchmark standards for outcome studies

Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation

One of the most frequent subtypes of constipation is represented by obstructed defecation, and it has recently been reported that these patients may have colonic motor abnormalities in addition to alterations of the anorectal area. However, it is unknown whether these patients display abnormalities of the enteric nervous system, as reported in other groups of constipated subjects. For this reason, we evaluated the neuropathologic aspects of the enteric nervous system in a homogeneous group of patients with obstructed defecation. Colonic specimens from 11 patients (nine women, age range 39–66 years) undergoing surgery for symptoms refractory to any therapeutic measure, including biofeedback training, were obtained and examined by means of conventional histological methods and immunohistochemistry (NSE, S100, c-Kit, formamide-mAb, Bcl-2, CD34, alfa-actin). Analysis of the specimens showed that the enteric neurons were significantly decreased only in the submucosal plexus of patients (P<0.0001 vs controls), whereas the enteric glial cells of constipated patients were reduced in both the myenteric (P=0.018 vs controls) and the submucosal plexus (P=0.004 vs controls). No difference between patients and controls were found concerning c-Kit and CD34 expression, and the number of apoptotic neurons. These findings support the concept that at least a subgroup of patients with obstructed defecation and severe, intractable symptoms display abnormalities of the enteric nervous system, mostly related to the enteric glial cells. These findings might explain some of the pathophysiological abnormalities, and help to better understand this condition.

Effectiveness and safety of local adalimumab injection in patients with fistulizing perianal Crohn's disease: a pilot study.

BACKGROUND:Various blockers of tumor necrosis factor-&agr; are available for treatment of Crohn’s disease. Randomized controlled trials have demonstrated the effects of systemic therapy with adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-&agr;. OBJECTIVE:The aim of this study was to investigate the effectiveness and safety of local injection of adalimumab along the fistula in the treatment of perianal Crohn’s disease. DESIGN AND SETTING:This was a prospective, uncontrolled, open-label observational study performed at a university tertiary care center. PATIENTS:A total of 12 outpatients (9 women, 3 men) treated for fistulizing perianal Crohn’s disease between 2009 and 2010 were enrolled. The mean age was 43.5 (range, 27–59) years. The fistula was classified as anovaginal in 3 patients, transsphincteric in 7 patients (low in 2, high in 5), and complex (multiple tracts) in 2 patients. Pikarsky’s Perianal Crohn’s Disease Activity Index was used to evaluate severity of the perianal disease. INTERVENTION:Adalimumab was injected locally along the fistula tract and around the internal orifice every 2 weeks. MAIN OUTCOME MEASURES:The primary end point of the study was the proportion of patients in whom complete or improved healing of fistulas was observed at follow-up, with improvement based on the number of daily changes of sanitary pads. RESULTS:The median number of injections per patient was 7 (range, 4–16). The mean length of follow-up was 17.5 (range, 5–30) months; 75% of patients (9 of 12) reached complete cessation of fistula drainage, and 3 patients (25%), all with transsphincteric fistula, showed improvement. Comparison of overall follow-up scores on the Perianal Crohn’s Disease Activity Index with baseline showed significant improvement (p = 0.002). No adverse side effects were noted. LIMITATIONS:The study was limited by its small sample size and by the absence of a control group. CONCLUSIONS:This pilot study suggests that a high local concentration of adalimumab favors prompt and definitive healing of the fistulous tract in patients with perianal Crohn’s disease. Future randomized trials with well-defined selection criteria are needed to determine the relative risks and benefits of available anti-TNF-&agr; blockers (chimeric vs fully humanized) and the optimal mode of administration (systemic use vs local injection) in the treatment of fistulizing perianal Crohn’s disease.

An assessment of enteric nervous system and estroprogestinic receptors in obstructed defecation associated with rectal intussusception

Background  The pathophysiological basis of obstructed defecation (OD) is still incompletely understood. In particular, few or no data are available concerning the enteric nervous system (ENS) in this condition. We investigated ENS abnormalities in patients with OD, undergoing surgery, together with the presence of estrogen (α and β) and progesterone receptors, and compare the results with those obtained in controls.

T1 colon cancer in the era of screening: risk factors and treatment.

BackgroundThe aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit.MethodsThe sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases.ResultsOut of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN.ConclusionsSome factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.

Multiple Enterocolic Perforations and Their Possible Association with Prolonged Intake of Nimesulide: Report of Two Cases

Nimesulide is a selective cyclooxygenase type 2 (COX2) inhibitor that, although having the characteristic antiinflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs), has better gastrointestinal tolerability (with less gastric and duodenal injury) than conventional nonselective cyclooxygenase inhibitors) (1). It is well known that toxicity in chronic NSAIDs users is not specific to the gastroduodenal tract. Over the past few years several reports have focused on the prevalence, clinical aspects, and pathogenesis of NSAIDs-induced adverse side effects (ASEs) on the small and large intestine, including diaphragm-like strictures, ulcerations, and perforations, associated with blood and protein loss (2‐5). The prevalence of NSAID-associated enteropathy in the upper gastroenteric tract (UGT) is approximately 20%, and among patients chronically taking NSAIDs the incidence of severe bleeding or perforation complications is 1t o2 %per year of use (6). Nevertheless, the assumption that enteropathy is mainly located in the UGT may be considered a bias, as demonstrated by retrospective, hospital-based, systemic studies showing that ASEs may sometimes have a higher prevalence in the lower gastroenteric tract (LGT) than in the UGT (7). Furthermore, a threeto-one ratio of large-versus-small bowel injuries (ulcers or perforations) was found (8). However, these intestinal complications were not reported in patients on nimesulide. A clinical survey carried out on a large population taking nimesulide gave no ev

Comparing outcomes after treatment of rectal cancer over a long-lasting follow-up between patients who were offered to surgery alone and to surgery with neoadjuvant therapy. A single center survey up to 240 months

BACKGROUND To assess outcomes of patients operated on for rectal cancer (RC) by analysing the trends of disease free survival curves (DFSc) after a very long-term follow-up. METHODS All patients treated with curative intent for RC from 1986 to 2005 were retrospectively analyzed. Other than demographics, disease characteristics and treatment-related factors were considered. The DFSc were compared between patients who had neoadjuvant therapy (NAT) and those who had surgery alone. RESULTS Median age of 319 patients included in the study was 66.3 years (range 23-89) and 140 (57.6%) of them were males. Moreover, NAT was given in 24 (11.8%) patients, and adjuvant therapy in 40 (19.7%) patients. Median follow-up was of 150 months (60-240). In patients who had NAT the mean age was higher (P=0.05), RC were located lower (P=0.009) and higher positive lymph-nodes were found (P=0.003), whereas the number of both local (P=0.4) and distant recurrences (P=0.7) was not significantly lower, compared to the other group. Comparing trends of DFSc a more progressive decrease was shown in patients treated with surgery alone. Even if the differences of DSFc between groups at the end of follow-up were not significant (95% CI: 0.609-2.963, P=0.46), patients who had NAT displayed better survival up to 180 months. CONCLUSIONS Overall, these results showed comparable outcomes between both groups over such a long lasting follow-up. This time frame might be used more extensively for increasing our knowledge of RC biological behaviour as well.

Does anaesthesia change severity of haemorrhoidal disease? A prospective and multicentre case-control study on haemorrhoidal disease assessment in two different settings: outpatient and operating theatre

Dear Editor: Haemorrhoidal disease (HD) still represents the most common proctologic disease characterised by anal discomfort and rectal bleeding. This condition has an enormous social impact with millions of people seeking for medical advises and surgical treatment. The classification of HD in four degrees proposed by Goligher is still accepted worldwide and is useful to drive the surgeons to choose a specific treatment but it cannot predict disease grade modifications due to relaxing effect of the anal canal secondary to anaesthesia. In fact, it is a common finding that the intraoperative picture of HD following anaesthesia is often worse. It means that the degree of HD observed in outpatient setting at the time of clinical evaluation does not always correspond to the features recorded in the operating room secondary to sphincter relaxation induced by anaesthesia, either loco-regional, spinal or general. The relaxation of the sphincter complex following anaesthesia simulates the normal relaxation of the anal canal at the time of defecation. In contrast, during examination and evaluation of the patients in the clinic, the anal canal may not be relaxed, preventing the patients from reproducing the haemorrhoidal prolapse to the same degree as during defecation. Therefore, the change of grade of HD, which can be observed before starting the surgical procedure, is with no doubts a predictable possibility. Moreover, in clinical practice, we observe a frequent association of internal mucosal prolapse (MP) to HD. It may be possible that preoperative assessment is made inaccurate by nonsphincter relaxation during outpatient visit and this can drive the surgeon to propose a surgical intervention that will not be effective for the treatment of the disease complained by the patient. We aimed to verify whether a different grade of HD including MP, is found comparing the outpatient work-up to the clinical evaluation performed preoperatively immediately after anaesthesia. Secondly, we checked if the previously planned surgical procedure will be modified by the possible change in HD grade, if any. From September 2012 to September 2014 a prospective multicentre study was run involving three different centres. Ethics Committee approvals were obtained by each participating centre. All consecutive patients planned to have surgery for HD under any form of anaesthesia and able to sign the informed consent were included. Patients with history of previous anal surgery and with any anal inflammatory disease or sepsis were excluded. Patients affected by full thickness rectal prolapse were excluded, also. The trial has been divided into two phases with a scheduled clinical assessment of the severity of HD at the time of the office evaluation (t1) and preoperatively immediately after anaesthesia (t2). First phase (t1): the patient was evaluated in the surgery office with a diagnostic workup including the digital examination, the use of rectoscope (up to 10 cm from anal This study has been accepted as a Free Paper presentation at the 10th Anniversary Meeting ESCP Dublin, 23–25 September 2015

Desmoid Tumours in Familial Adenomatous Polyposis

The term desmoid was first used by Muller [1] to describe the tendon-like aspect and the hard consistency of this type of proliferation (desmos in Greek means band). Desmoid tumours (DTs) are classified as extraor intra-abdominal. The extra-abdominal DTs arise from fascial or musculoaponeurotic structures predominantly of the abdominal wall (Fig. 1a, b, c) and occasionally of the shoulder girdle, chest wall, inguinal region and extremities. They present as a firm, smooth, painless, progressively growing mass. Imaging investigations are useful in better defining the extent of the tumour which displays an iceberg growth with only a small proportion being clinically manifest. Interestingly, multiple extra-abdominal DTs are frequently discovered in very young patients under the age of 3 [2]. The intra-abdominal DTs develop in the folds of the mesentery or the mesocolon (Fig. 2a, b) even reaching the retroperitoneal tissue or they may grow exclusively in this region. These proliferations are usually single, round or oval in shape and up to 60 cm in size. Rather than a mass, a thickening of the mesentery that appears to be covered with hard white spots and causes retraction of the peritoneal folds is frequently reported in familial Desmoid Tumours in Familial Adenomatous Polyposis