Mannosylerythritol lipids (MEL) are glycolipids with unique biosurfactant properties and are produced by Pseudozyma spp. from different substrates, preferably vegetable oils, but also sugars, glycerol or hydrocarbons. However, solvent intensive downstream processing and the relatively high prices of raw materials currently used for MEL production are drawbacks in its sustainable commercial deployment. The present work aims to demonstrate MEL production from cellulosic materials and investigate the requirements and consequences of combining commercial cellulolytic enzymes and Pseudozyma spp. under separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) processes. MEL was produced from cellulosic substrates, Avicel® as reference (>99% cellulose) and hydrothermally pretreated wheat straw, using commercial cellulolytic enzymes (Celluclast 1.5 L® and Novozyme 188®) and Pseudozyma antarctica PYCC 5048T or Pseudozyma aphidis PYCC 5535T. The strategies included SHF, SSF and fed-batch SSF with pre-hydrolysis. While SSF was isothermal at 28°C, in SHF and fed-batch SSF, yeast fermentation was preceded by an enzymatic (pre-)hydrolysis step at 50°C for 48 h. Pseudozyma antarctica showed the highest MEL yields from both cellulosic substrates, reaching titres of 4.0 and 1.4 g/l by SHF of Avicel® and wheat straw (40 g/l glucan), respectively, using enzymes at low dosage (3.6 and 8.5 FPU/gglucan at 28°C and 50°C, respectively) with prior dialysis. Higher MEL titres were obtained by fed-batch SSF with pre-hydrolysis, reaching 4.5 and 2.5 g/l from Avicel® and wheat straw (80 g/l glucan), respectively. This work reports for the first time MEL production from cellulosic materials. The process was successfully performed through SHF, SSF or Fed-batch SSF, requiring, for maximal performance, dialysed commercial cellulolytic enzymes. The use of inexpensive lignocellulosic substrates associated to straightforward downstream processing from sugary broths is expected to have a great impact in the economy of MEL production for the biosurfactant market, inasmuch as low enzyme dosage is sufficient for good systems performance.

Goal. To evaluate the prognostic value of Mandard and Dworak grading systems regarding neoadjuvant chemoradiotherapy (CRT) response on rectal cancer. Materials and Methods. We queried our center’s database for patients with colo rectal cancer with locally advanced rectal cancer (LARC) who received neoadjuvant CRT followed by total mesorectum excision (TME) between 2003 and 2011. After excluding 18 patients from the initial query the remaining 139 were reassessed for disease recurrence and survival; the specimens’ slides were reviewed and classified according to two tumor regression grading (TRG) systems: Mandard and Dworak. Based on these TRG scores, two patient groups were created: patients with good response versus patients with bad response (Mandard TRG1+2 versus Mandard TRG3+4+5 and Dworak TRG4+3 versus Dworak TRG2+1+0). Overall survival (OS), disease-free survival (DFS), and disease recurrence were then evaluated. Results. Mean age was 64.2 years and median follow up was 56 months. No significant survival difference was found when comparing patients with Dworak TRG 4+3 versus Dworak TRG2+1+0 (P=0.10). Mandard TRG1+2 presented with significantly better OS and DFS than Mandard TRG3+4+5 (OS P=0.013; DFS P=0.007). Conclusions. Mandard system provides higher accuracy over Dworak system in predicting rectal cancer prognosis when neoadjuvant CRT is applied for tumor regression.

Introduction: This study aimed to assess the clinical, economic, and humanistic impact of short-bowel syndrome/chronic intestinal failure (SBS/CIF) in Portugal. Methods: This is a retrospective multicenter cohort chart review study, with a cross-sectional component for quality-of-life (QoL) evaluation. Inclusion criteria comprised patients with SBS/CIF, aged ≥1 year, with stable parenteral nutrition (PN). Data collection included patient chart review over a 12-month period and patient/caregiver self-report and SF-36/PedsQL™ questionnaires. Main endpoints comprised clinical and PN characterization, healthcare resource use (HRU), direct costs, and patient QoL. Results: Thirty-one patients were included (11 adults and 20 children). Patients’ mean age (standard deviation [SD]) was 57.9 (14.3) years in adults and 7.5 (5.0) years in children, with a mean time since diagnosis of 10.2 (5.9) and 6.6 (4.2) years, respectively. PN was administered for a mean of 5.2 and 6.6 days/week in adults and children, respectively; home PN occurred in 81.8% of adults and 90.0% of children for a mean of 9.6 and 10.8 months/year, respectively. The mean annual number of hospitalizations was 1.9 and 2.0 which lasted for a mean of 34.0 and 29.4 days in adults and children, respectively. Twenty-one and forty hospitalization episodes were reported in adults and children, respectively, of which 71.4% and 85.0% were due to catheter-related complications. Mean annual direct costs per patient amounted to 47,857.53 EUR in adults and 74,734.50 EUR in children, with PN and hospitalizations as the main cost-drivers. QoL assessment showed a clinically significant impaired physical component in adults and a notable deterioration in the school functioning domain in children. Conclusion: In Portugal, SBS/CIF patient management is characterized by a substantial therapeutic burden and HRU, translating into high direct costs and a substantial impairment of the adults’ physical function and children’s school functioning.

Background. Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC).Materials and Methods. We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the slides of surgical specimens were reviewed and classified according to Mandard tumor regression grades (TRG). We compared patients with good response (Mandard TRG1 or TRG2) versus patients with bad response (Mandard TRG3, TRG4, or TRG5). Outcomes evaluated were 5-year overall survival (OS), disease-free survival (DFS), local, distant and mixed recurrence.Results. Mean age was 64.2 years, and median followup was 56 months. No statistically significant survival difference was found when comparing patients with Mandard TRG1 versus Mandard TRG2 (). Mandard good responders (TRG1 + 2) have significantly better OS and DFS than Mandard bad responders (TRG3 + 4 + 5) (OS ; DFS ).Conclusions. Mandard good responders had a favorable prognosis. Tumor response (TRG) to neoadjuvant chemoradiation should be taken into account when defining the optimal adjuvant chemotherapy regimen for patients with LARC.

Chronic perianal fistulas are a common clinical condition. However, their evolution to adenocarcinoma is rare. We report the case of a 48-year-old man with perianal chronic fistulas, who developed two perianal ulcerated lesions near the external orifices of the fistulas, which extended proximally as a pararectal tumor. No intestinal lesion was seen at endoscopic examination. Histopathological biopsy indicated mucinous adenocarcinoma. Staging was performed by pelvic magnetic resonance imaging (MRI) and thoracoabdominal CT scan. The patient underwent a laparoscopic colostomy followed by neoadjuvant chemoradiotherapy and then laparoscopic abdominoperineal resection followed by adjuvant therapy. We have seen a favorable outcome with no recurrence at 3 years of follow-up.