Perineal wound healing after abdominoperineal resection for rectal cancer: a two-centre experience in the era of intensified oncological treatment.

PURPOSE: Intensified treatment for distal rectal cancer has improved oncological outcome, but at the expense of more perineal wound complications in patients undergoing an abdominoperineal resection (APR). The aim of this study was to analyse perineal wound healing after APR with primary perineal wound closure over time. METHOD: All patients undergoing APR for primary rectal cancer with primary wound closure between 2000 and 2013 were included and analysed in three consecutive time periods. Both early (<30 days postoperatively) and late perineal wound complications were determined. Independent risk factors of early perineal wound complications were identified using multivariable analysis. RESULTS: A total of 136 patients were identified, of whom 129 patients underwent primary perineal wound closure. The use of neo-adjuvant (chemo)radiotherapy increased from 72 to 91%, and the use of an extralevator approach increased from 9 to 19%. The rate of early perineal wound complications increased from 18 to 31% and was independently associated with an extralevator approach [odds ratio (OR) 3.17; 95% confidence interval (CI) 1.16-8.66] and intra-operative perforation (OR 3.35; 95% CI 1.06-10.57). Perineal wound complications had no impact on local recurrence or 3-year overall survival rate. During a median follow-up of 28 months [interquartile range (IQR) 14-56], a persistent presacral sinus was diagnosed in 10%, and a perineal hernia occurred in 8% of the patients. CONCLUSION: The increased use of an extralevator APR for rectal cancer significantly increased the risk of perineal wound complications over time. Intra-operative perforation was also independently associated with impaired perineal wound healing.

Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate.

Metachromatic leukodystrophy (MLD) is a lethal neurodegenerative disease caused by a deficiency in the lysosomal arylsulfatase A (ARSA) enzyme leading to the accumulation of sulfatides in glial and neuronal cells. We previously demonstrated in ARSA-deficient mice that intracerebral injection of a serotype 5 adeno-associated vector (AAV) encoding human ARSA corrects the biochemical, neuropathological and behavioral abnormalities. However, before considering a potential clinical application, scaling-up issues should be addressed in large animals. Therefore, we performed intracerebral injection of the same AAV vector (total dose of 3.8 x 10(11) or 1.9 x 10(12) vector genome, three sites of injection in the right hemisphere, two deposits per site of injection) into three selected areas of the centrum semiovale white matter, or in the deep gray matter nuclei (caudate nucleus, putamen, thalamus) of six non-human primates to evaluate vector distribution, as well as expression and activity of human ARSA. The procedure was perfectly tolerated, without any adverse effect or change in neurobehavioral examination. AAV vector was detected in a brain volume of 12-15 cm(3) that corresponded to 37-46% of the injected hemisphere. ARSA enzyme was expressed in multiple interconnected brain areas over a distance of 22-33 mm. ARSA activity was increased by 12-38% in a brain volume that corresponded to 50-65% of injected hemisphere. These data provide substantial evidence for potential benefits of brain gene therapy in patients with MLD.

Colorectal cancer at high risk of peritoneal metastases: long term outcomes of a pilot study on adjuvant laparoscopic HIPEC and future perspectives.

OBJECTIVE: Early detection of peritoneal metastases (PM) of colorectal cancer (CRC) is difficult and treatment options at a clinically overt stage are limited. Potentially, adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) is of value. The aim of this study was to present long term oncological outcomes of a pilot study on adjuvant HIPEC to reduce development of PMCRC, with systematic review of literature. METHODS: Long term oncological outcomes of ten patients who underwent laparoscopic HIPEC within eight weeks after resection of primary CRC in the pilot study were retrospectively collected. A systematic search of literature was performed on studies describing the use of HIPEC in patients with CRC at high risk of developing PM. RESULTS: The median follow-up was 54 months (range 49-63). All patients were alive at the last follow-up moment and none of them had developed PM. Two patients had developed pulmonary metastases. Systematic review revealed five small cohort studies, including two matched comparisons. Peritoneal recurrences were found in 0% to 9% after adjuvant HIPEC, which was 28% and 43% in the two control groups, respectively. Disease free and overall survival were significantly higher in favour of HIPEC. CONCLUSION: Long term follow-up of ten patients included in a pilot study on adjuvant HIPEC revealed no peritoneal recurrences. This result is in line with other published pilot studies, a promising observation. However, the outcomes of the Dutch randomized COLOPEC trial and similar trials worldwide should be awaited for definitive conclusions on the effectiveness of adjuvant HIPEC.