Total Laparoscopic Restorative Proctocolectomy: Are There Advantages Compared with the Open and Hand-Assisted Approaches?

PURPOSE: A randomized, controlled trial comparing hand-assisted laparoscopic restorative proctocolectomy with open surgery did not show an advantage for the laparoscopic approach. The trial was criticized because hand-assisted laparoscopic restorative proctocolectomy was not considered a true laparoscopic proctocolectomy. The objective of the present study was to assess whether total laparoscopic restorative proctocolectomy has advantages over hand-assisted laparoscopic restorative proctocolectomy with respect to early recovery. METHODS: Thirty-five patients underwent total laparoscopic restorative proctocolectomy and were compared to 60 patients from a previously conducted randomized, controlled trial comparing hand-assisted laparoscopic restorative proctocolectomy and open restorative proctocolectomy. End points included operating time, conversion rate, reoperation rate, hospital stay, morbidity, quality of life, and costs. The Medical Outcomes Study Short Form 36 and the Gastrointestinal Quality of Life Index were used to evaluate general and bowel-related quality of life. RESULTS: Groups were comparable for patient characteristics, such as sex, body mass index, preoperative disease duration, and age. There were neither conversions nor intraoperative complications. Median operating time was longer in the total laparoscopic compared with the hand-assisted laparoscopic group (298 vs. 214 minutes; P < 0.001). Morbidity and reoperation rates in the total laparoscopic, hand-assisted laparoscopic, and open groups were comparable (29 vs. 20 vs. 23 percent and 17 vs.10 vs. 13 percent, respectively). Median hospital-stay was 9 days in the total laparoscopic group compared with 10 days in the hand-assisted laparoscopic group and 11 days in the open group (P = not significant). There were no differences in quality of life and total costs. CONCLUSIONS: There were no significant short-term benefits for total laparoscopic compared with hand-assisted laparoscopic restorative proctocolectomy with respect to early morbidity, operating time, quality of life, costs, and hospital sta

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease

Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme acting in the catabolism of the widely used antineoplastic agent 5-fluorouracil (5FU). DPD deficiency is known to cause a potentially lethal toxicity following administration of 5FU. Here, we report novel genetic mechanisms underlying DPD deficiency in patients presenting with grade III/IV 5FU-associated toxicity. In one patient a genomic DPYD deletion of exons 21–23 was observed. In five patients a deep intronic mutation c.1129–5923C>G was identified creating a cryptic splice donor site. As a consequence, a 44 bp fragment corresponding to nucleotides c.1129–5967 to c.1129–5924 of intron 10 was inserted in the mature DPD mRNA. The deleterious c.1129–5923C>G mutation proved to be in cis with three intronic polymorphisms (c.483 + 18G>A, c.959–51T>G, c.680 + 139G>A) and the synonymous mutation c.1236G>A of a previously identified haplotype. Retrospective analysis of 203 cancer patients showed that the c.1129–5923C>G mutation was significantly enriched in patients with severe 5FU-associated toxicity (9.1%) compared to patients without toxicity (2.2%). In addition, a high prevalence was observed for the c.1129–5923C>G mutation in the normal Dutch (2.6%) and German (3.3%) population. Our study demonstrates that a genomic deletion affecting DPYD and a deep intronic mutation affecting pre-mRNA splicing can cause severe 5FU-associated toxicity. We conclude that screening for DPD deficiency should include a search for genomic rearrangements and aberrant splicing