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Purpose: In the attempt to understand the reasons for and to find a solution to the high recurrence rate after perineal surgery for complete rectal prolapse, we retrospectively analysed the long-term results of Altemeier's procedure alone, or associated with Trans-Obturator Colonic Suspension (TOCS) in a large series of patients with a median interval of 84 months (range 6-258)., Methods: Medical records of 110 patients undergoing Altemeier with levatorplasty (group 1) and 20 patients submitted to the same procedure associated with TOCS (group 2) for newly diagnosed complete rectal prolapse were reviewed. All patients had been recruited after preoperative clinical examination, SF-36 quality of life, continence score and colonoscopy., Results: Mortality was nil. The overall complication and the recurrence rates were 12.3%, and 15.0% (P= 0.769) and 24.6% and 5.0% (P=0.067) in group 1 and 2, respectively. Twelve patients of group 1 with a recurrence were submitted to a redo-Altemeier, 8 to a redo-Altemeier associated with TOCS, and 6 associated with an anterior coloplasty with a mesh. The only patient of group 2 with a recurrence was submitted to a Hartmann's operation. Preoperative vs postoperative mean (SD) continence score was 15.8 (3.1) and 15.6 (3.3) versus 4.1 (1.8) and 3.9 (1.9) in group 1 and 2, respectively (P < 0.001). All parameters of SF-36 improved after surgery (P<0.01) and no differences between the 2 groups were found CONCLUSIONS: Long-term results confirmed the safety and effectiveness of Altemeier's procedure for the treatment of complete rectal prolapse, with the limit of a non-negligible incidence of anastomotic complications and recurrences. The combination of Altemeier with TOCS showed a positive trend to a reduction of the recurrence rate, not worsening morbidity and outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: The aim of this prospective study was to assess the safety and effectiveness of a new single laparoscopic operation devised to relieve obstructed defecation, gynecologic and urinary symptoms in a large series of female patients with multiorgan pelvic prolapse., Methods: We submitted 384 female patients to laparoscopic pelvic organ prolapse suspension operation, a new technique based on suspension of the middle pelvic compartment, by using a polypropylene mesh and followed up 368 of them, with defecography performed 12 months after surgery and a standardized protocol., Results: The 368 patients were followed-up for 36.3 (±4.4) months, Recurrence rate was 4.9% for obstructed defecation syndrome and 3.3% for stress urinary incontinence. Complication rate was 2.9%. The mean period of daily activity resumption was 16.3 days (±4.8 days). Anorectal and urogynecologic symptoms and scores significantly improved after the operation (P < 0.001), with no worsening of anal continence. Incidence of postoperative fecal urgency was 0%. Postoperative defecography showed a significant (P < 0.001) improvement of all parameters in 315 patients (82%). Short Form 36 Health Survey score significantly improved after the operation (P < 0.01). An excellent/good overall Satisfaction Index was reported by 78.0% of patients., Conclusions: In our experience the Laparoscopic-Pelvic Organ Prolapse Suspension seems to be safe and effective as a 1-stage treatment of associated pelvic floor diseases. Randomized studies with an appropriate control group and longer follow-up are now needed to assess the effectiveness of this promising technique., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2019 American Urogynecologic Society. All rights reserved.)

Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK - a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

A randomized study was carried out to compare the mid-term outcome of transanal rectal resection with the CCS-30 TRANSTAR and two TST36 staplers in patients with obstructed defecation syndrome. After selection, patients were randomly assigned to 2 groups:104 underwent a TRANSTAR operation and 104 a transanal rectal resection with two TST36 staplers. Patients were followed up with clinical examination, and defecography. Cumulative complication rate was significantly higher in TRANSTAR operation (P = 0.019). All symptoms and defecographic parameters significantly improved (P < 0.001), without differences. Costs were significantly lower with double TST (P = 0.035). Recurrence rates were 6.2% in TRANSTAR group and 11.4% with double TST (P = 0.206). Two circular TST 36 staplers consent to obtain the same clinical and functional results than the CCS-30, with significantly lower complication rate and costs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Glycogen Synthase Kinase-3 alpha (GSK3A) and beta (GSK3B) isoforms are encoded by distinct genes, are 98% identical within their kinase domain and perform similar functions in several settings; however, they are not completely redundant and, depending on the cell type and differentiative status, they also play unique roles. We recently identified a role for GSK3B in drug resistance by demonstrating that its inhibition enables necroptosis in response to chemotherapy in p53-null drug-resistant colon carcinoma cells. We report here that, similarly to GSK3B, also GSK3A silencing/inhibition does not affect cell proliferation or cell cycle but only abolishes growth after treatment with DNA-damaging chemotherapy. In particular, blocking GSK3A impairs DNA repair upon exposure to DNA-damaging drugs. As a consequence, p53-null cells overcome their inability to undergo apoptosis and mount a necroptotic response, characterized by absence of caspase activation and RIP1-independent, PARP-dependent AIF nuclear re-localization. We therefore conclude that GSK3A is redundant with GSK3B in regulating drug-resistance and chemotherapy-induced necroptosis and suggest that inhibition of only one isoform, or rather partial inhibition of overall cellular GSK3 activity, is enough to re-sensitize drug-resistant cells to chemotherapy.

Introduction: The stapled transanal rectal resection (STARR) procedure is safe and effective., Objective of the Study: To compare STARR performed with PPH-01 (STARR) and CCS 30 (Transtar)., Materials and Methods: Sixty-four patients underwent STARR for obstructed defecation syndrome (32 STARR and 32 Transtar) and were observed from January 2007 to June 2009. Patients were studied by visit with questionnaires, colonoscopy or barium enema, defecography, and anorectal manometry. Postoperatively they were assessed through visit and questionnaires., Results: All patients improved symptoms without statistical differences. The obstructed defecation syndrome score changed from 13 to 1.8 at 6 months and to 1 at 1 year in the STARR group (P < .05), and the score changed from 15 to 2 at 6 months and to 1 at 1 year in the Transtar group (P < .05). There were no intraoperative complications in the STARR group, but there were 2 dehiscences of suture in the Transtar group. There were no differences with regard to complications., Conclusion: Transtar is a more complex technique with more severe complications. A major resection is not always more effective.

The authors report a rare case of composite tumour of the stomach in a 53-year-old woman documenting the neuroendocrine and glandular features of the tumour by means of immunohistochemical investigations. The authors examine the diagnostic and therapeutic possibilities currently available for the management of this group of rare tumours of uncertain histogenesis. They conclude in favour of elective surgical treatment depending on the site and stage of the tumour in keeping with the data reported in the literature. They also discuss the prognosis of such tumours.