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1.  Switching from a Unicellular to Multicellular Organization in an Aspergillus niger Hypha 
mBio  2015;6(2):e00111-15.
Pores in fungal septa enable cytoplasmic streaming between hyphae and their compartments. Consequently, the mycelium can be considered unicellular. However, we show here that Woronin bodies close ~50% of the three most apical septa of growing hyphae of Aspergillus niger. The incidence of closure of the 9th and 10th septa was even ≥94%. Intercompartmental streaming of photoactivatable green fluorescent protein (PA-GFP) was not observed when the septa were closed, but open septa acted as a barrier, reducing the mobility rate of PA-GFP ~500 times. This mobility rate decreased with increasing septal age and under stress conditions, likely reflecting a regulatory mechanism affecting septal pore diameter. Modeling revealed that such regulation offers effective control of compound concentration between compartments. Modeling also showed that the incidence of septal closure in A. niger had an even stronger impact on cytoplasmic continuity. Cytoplasm of hyphal compartments was shown not to be in physical contact when separated by more than 4 septa. Together, data show that apical compartments of growing hyphae behave unicellularly, while older compartments have a multicellular organization.
The hyphae of higher fungi are compartmentalized by porous septa that enable cytosolic streaming. Therefore, it is believed that the mycelium shares cytoplasm. However, it is shown here that the septa of Aspergillus niger are always closed in the oldest part of the hyphae, and therefore, these compartments are physically isolated from each other. In contrast, only part of the septa is closed in the youngest part of the hyphae. Still, compartments in this hyphal part are physically isolated when separated by more than 4 septa. Even open septa act as a barrier for cytoplasmic mixing. The mobility rate through such septa reduces with increasing septal age and under stress conditions. Modeling shows that the septal pore width is set such that its regulation offers maximal control of compound concentration levels within the compartments. Together, we show for the first time that Aspergillus hyphae switch from a unicellular to multicellular organization.
PMCID: PMC4357997  PMID: 25736883
2.  Repair of Parastomal Hernias with Biologic Grafts: A Systematic Review 
Journal of Gastrointestinal Surgery  2011;15(7):1252-1258.
Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias.
Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms ‘paracolostomy’, ‘paraileostomy’, ‘parastomal’, ‘colostomy’, ‘ileostomy’, ‘hernia’, ‘defect’, ‘closure’, ‘repair’ and ‘reconstruction’ were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity.
Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8–25.9) of patients and wound-related complications in 26.2% (95% CI 14.7–39.5). No mortality or graft infections were reported.
The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts.
PMCID: PMC3116129  PMID: 21360207
Biologic graft; Allograft; Xenograft; Parastomal hernia
3.  Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin 
Annals of Surgical Oncology  2009;16(7):2065-2073.
Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases.
Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 × 106 CC531 tumor cells. The biodistribution of 111In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of 177Lu-labeled MG1 was determined and the therapeutic efficacy of 177Lu-MG1 at MTD was compared with that of 177Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival.
111In-MG1 preferentially accumulated in CC531 liver tumors (9.2 ± 3.7%ID/g), whereas 111In-UPC-10 did not (0.8 ± 0.1%ID/g). The MTD of 177Lu-MG1 was 400 MBq/kg body weight. Both the administration of 177Lu-MG1 and 177Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received 177Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of 177Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of 177Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940).
This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.
PMCID: PMC2695874  PMID: 19430843
4.  Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial) 
BMC Surgery  2008;8:15.
With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.
The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs.
The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007.
The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease.
Trial registration
Nederlands Trial Register NTR1150
PMCID: PMC2533646  PMID: 18721465
5.  Incidence and Risk Factors of Recurrence after Surgery for Pathology-proven Diverticular Disease 
World Journal of Surgery  2008;32(7):1501-1506.
Diverticular disease is a common problem in Western countries. Rationale for elective surgery is to prevent recurrent complicated diverticulitis and to reduce emergency procedures. Recurrent diverticulitis occurs in about 10% after resection. The pathogenesis for recurrence is not completely understood. We studied the incidence and risk factors for recurrence and the overall morbidity and mortality of surgical therapy for diverticular disease.
Medical records of 183 consecutive patients with pathology-proven diverticulitis were eligible for evaluation. Mean duration of follow-up was 7.2 years. Number of preoperative episodes, emergency or elective surgeries, type of operation, level of anastomosis, postoperative complications, persistent postoperative pain, complications associated with colostomy reversal, and recurrent diverticulitis were noted. The Kaplan-Meier method was used to calculate the cumulative probability of recurrence. Cox regression was used to identify possible risk factors for recurrence.
The incidence of recurrence was 8.7%, with an estimated risk of recurrence over a 15-year period of 16%. Risk factors associated with recurrence were (younger) age (p < 0.02) and the persistence of postoperative pain (p < 0.005). Persistent abdominal pain after surgery was present in 22%. Eighty percent of patients who needed emergency surgery for acute diverticulitis had no manifestation of diverticular disease prior to surgery. In addition, recurrent diverticulitis was not associated with a higher percentage of emergency procedures.
Estimated risk of recurrence is high and abdominal complaints after surgical therapy for diverticulitis are frequent. Younger age and persistence of postoperative symptoms predict recurrent diverticulitis after resection. The clinical implication of these findings needs further investigation. The results of this study support the careful selection of patients for surgery for diverticulitis.
PMCID: PMC2480508  PMID: 18330623

Results 1-5 (5)