Newly established tumourigenic primary human colon cancer cell lines are sensitive to TRAIL-induced apoptosis in vitro and in vivo

Most data on the therapeutic potential of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) as well as resistance to FAS ligand (FASL) in colorectal cancer have come from in vitro studies using cell lines. To gain a clearer understanding about the susceptibility of patient tumours to TRAIL and FASL, we derived primary human cancer epithelial cells from colon cancer patients. Characterisation of primary cultures PAP60 and MIH55 determined their highly proliferating advantage, transforming capability and tumorigenicity in vitro and in vivo. Although FASL treatment appeared to cause little apoptosis only in the PAP60 primary culture, increased apoptosis independent of p53 was observed in both primary PAP60 and MIH55 and control cell lines Caco-2, HT29 and DLD-1 after treatment with SuperKiller TRAIL. Expression analysis of death receptors (DR) in the original parental tumours, the primary cultures before and after engraftment as well as the mouse xenografts, revealed a significant upregulation of both DR4 and DR5, which correlated to differences in sensitivity of the cells to TRAIL-induced apoptosis. Treating patient tumour xenograft/SCID mouse models with Killer TRAIL in vivo suppressed tumour growth. This is the first demonstration of TRAIL-induced apoptosis in characterised tumorigenic primary human cultures (in vitro) and antitumour activity in xenograft models (in vivo)

Pseudo-colonic obstruction after lumbar spine surgery: a case report.

Acute colonic pseudo-obstruction (Ogilvie's syndrome) is characterised by abdominal distension and massive colonic dilatation without any mechanical cause of obstruction. The pathogenesis remains unknown but likely involves imbalance between sympathetic and parasympathetic colon innervation. This syndrome is well known in orthopaedic surgery, as trauma and orthopaedic surgery have been reported as aetiological factors. Some cases have been reported after cervical discectomy. We report a case of Ogilvie's syndrome after lumbar spine surgery. Medical treatment including parasympathetic agent was unsuccessful and the patient underwent a right colectomy. The pathophysiology and treatment are discussed based on a review of the literature.Case ReportsJournal Articleinfo:eu-repo/semantics/publishe

Should ruptured liver haemangioma be treated by surgery or by conservative means? A case report.

Spontaneous rupture of a liver haemangioma is a rare but life-threatening acute clinical situation following haemorrhage within the liver, the subcapsular space and the peritoneal cavity in cases of capsular rupture. Rupture of a liver haemangioma has been reported to occur spontaneously in the majority of cases. In the past, prompt surgical treatment was recommended but was associated with high morbidity and mortality. Currently, conservative management and, in cases of recurrent haemorrhage, delayed surgery may be proposed. We report a case of spontaneous rupture of hepatic haemangioma treated by arterial embolisation and conservative means. The literature is also reviewed.Case ReportsJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Consensus guidelines for pressurized intraperitoneal aerosol chemotherapy: Technical aspects and treatment protocols: PIPAC practice guidelines

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to treat patients with peritoneal cancer. A recent survey demonstrated considerable diversification of current practice of PIPAC raising issues of concern also regarding safety and efficacy. The study aim was to reach consensus on best practice of PIPAC treatment. Methods: Current practice was critically discussed during an expert meeting and the available evidence was scrutinized to elaborate a 33-item closed-ended questionnaire. All active PIPAC centers were then invited to participate in an online two-round Delphi process with 3 reminders at least. Consensus was defined a priori as >70% agreement for a minimal response rate of 70%. Results: Forty-nine out of 57 invited PIPAC centers participated in Delphi 1 and 2 (86%). Overall, there was agreement for 21/33 items. Consensus was reached for important aspects like advanced OR ventilation system (91.8%), remote monitoring (95.9%), use of the PRGS (85.7%) and use of a safety checklist (98%). The drug regimens oxaliplatin (87.8%) and cisplatin/doxorubicin (81.6%) were both confirmed by the expert panel. Important controversies included number and location of Biopsies during repeated PIPAC and the combination of PIPAC with additional surgical procedures. Conclusion: This consensus statement aims to allow for safe and efficacious PIPAC treatment and to facilitate multi-center analyses of the results. Additional preclinical and clinical studies are needed to resolve the remaining controversies

Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study

Background: PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. Methods: PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. Results: the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. Conclusions: these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available

Current practice of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Still standardized or on the verge of diversification? Current practice of PIPAC

Background: PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications. Methods: A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6). Results: Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program. Conclusion: Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement