Risks of combining immunosuppressive and biological treatments in inflammatory bowel disease - in reply

We thank Roblin and Phelip for their comment on a timely issue. The recent report of the rare hepatosplenic T-cell lymphoma (HSTCL) in young patients with CD treated with both infliximab and azathioprine or steroids has rightly unleashed a series of doubts regarding the optimal use of biological agents in this and other conditions. How these observations may directly relate to the design of our study\u2014as implied by Roblin and Phelip\u2014is unclear though. While azathioprine by itself has been linked to lymphoma development including HSTCL, recent studies have shown that neither infliximab nor methotrexate, which was used in our study, alone or in combination in CD or in rheumatoid arthritis, appear to be associated with an increased risk of developing lymphomas. In addition, methotrexate alone has never been associated thus far with HSTCL in CD

Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer – A Case Report

Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia

Long-Term Functional Outcome after Internal Delorme's Procedure for Obstructed Defecation Syndrome, and the Role of Postoperative Rehabilitation

PURPOSE: To evaluate long-term functional outcomes of Internal Delorme's Procedure (IDP) in patients refractory to conservative treatment for Obstructed Defecation Syndrome (ODS), and to compare those who received postoperative rehabilitation with those who did not. MATERIALS AND METHODS: All patients with ODS refractory to nonoperative therapy were identified across three regional pelvic floor referral hospitals, and IDP was performed. Postoperatively selected patients received biofeedback therapy. Functional outcomes were established using the Cleveland Clinic Constipation (CCC) score and obstructed defecation score (OD score) preoperatively at 12 months and at the last available follow-up. Patient satisfaction was assessed with a visual analogue score. RESULTS: From October 2006 to September 2013, IDP was performed in 170 patients: 77 received postoperative biofeedback and 93 did not. Mean follow-up was 6.3 years (range 1-8 years). CCC and OD scores improved significantly in both groups after 12 months and at the last follow-up (p > 0.05). When comparing two groups while there was no significant difference between CCC and OD scores at 12 months, score was significantly better in the group that received rehabilitation at the last follow-up (p = 0.001). Patient satisfaction was higher in the rehabilitation group (67%) compared with those without rehabilitation (55%). Clinical recurrence was recorded in nine patients who did not have postoperative rehabilitation. CONCLUSIONS: It has been demonstrated that IDP is associated with good long-term functional outcomes. Patients receiving rehabilitation had a better long-term follow-up, a higher overall satisfaction, and lower recurrence rate when compared with the patients who did not receive postoperative rehabilitation

Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway

The pathogenesis of colorectal cancer (CRC) involves different mechanisms, such as genomic and microsatellite instabilities. Recently, a contribution of the base excision repair (BER) pathway in CRC pathology has been emerged. In this context, the involvement of APE1 in the BER pathway and in the transcriptional regulation of genes implicated in tumor progression strongly correlates with chemoresistance in CRC and in more aggressive cancers. In addition, the APE1 interactome is emerging as an important player in tumor progression, as demonstrated by its interaction with Nucleophosmin (NPM1). For these reasons, APE1 is becoming a promising target in cancer therapy and a powerful prognostic and predictive factor in several cancer types. Thus, specific APE1 inhibitors have been developed targeting: i) the endonuclease activity; ii) the redox function and iii) the APE1-NPM1 interaction. Furthermore, mutated p53 is a common feature of advanced CRC. The relationship between APE1 inhibition and p53 is still completely unknown. Here, we demonstrated that the inhibition of the endonuclease activity of APE1 triggers p53-mediated effects on cell metabolism in HCT-116 colon cancer cell line. In particular, the inhibition of the endonuclease activity, but not of the redox function or of the interaction with NPM1, promotes p53 activation in parallel to sensitization of p53-expressing HCT-116 cell line to genotoxic treatment. Moreover, the endonuclease inhibitor affects mitochondrial activity in a p53-dependent manner. Finally, we demonstrated that 3D organoids derived from CRC patients are susceptible to APE1-endonuclease inhibition in a p53-status correlated manner, recapitulating data obtained with HCT-116 isogenic cell lines. These findings suggest the importance of further studies aimed at testing the possibility to target the endonuclease activity of APE1 in CRC

Presence of Bacillus cereus, Escherichia coli and Enterobacteriaceae in fresh and salted Ricotta cheese: official controls in Sardinia during the period 2009 – 2012.

Results of microbiological official analysis carried out during 2009-2012 for detection of Bacillus cereus, Escherichia coli and Enterobacteriaceae in fresh and salted Ricotta cheese marketed in Sardinia, are re-ported. The aim of this research was to evaluate the presence of contaminants indicators of process hy-giene, and the presence of B. cereus, which while not covered in the EC Regulation 2073/05 for this product, it may represent a risk as a potential producer of toxins harmful to the consumer health. Were analyzed a total of 157 samples according to ISO reference. The results indicate a widespread presence of the three types of microorganisms sought: prevalence of B. cereus 53%, 23% Enterobacteriaceae, E. coli 12%. In conclusion, it is desirable the introduction, in the production process, keeping the cold chain to prevent the risk from B. cereus, and improved hygiene of processing plant, equipment and personnel, to reduce recontamination of the product by the Enterobacteriaceae and E. coli

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