Surgical site infection rates: open versus hand-assisted colorectal resections.

PURPOSE: This study was performed to determine impact of open and hand-assisted colorectal resection on surgical site infection (SSI) rates. METHODS: National Surgical Quality Improvement Project data from 2006 to 2008 were supplemented with an institutional review board-approved chart review. Primary endpoint was SSI rates defined by the Centers for Disease Control National Nosocomial Infections Surveillance system and classified as superficial, deep incisional, and organ space. Inclusion criteria were elective or emergency open or hand-assisted colorectal resections. Wounds were classified as clean-contaminated, contaminated, or dirty-infected. Patients were not included if they underwent laparoscopic colorectal resection, small bowel resection, or stoma creation. RESULTS: Two hundred and forty-five consecutive patients were included over a 29-month period. One hundred and ninety-five open and 50 hand-assisted patients were comparable for gender, body mass index, ethnicity, tobacco addiction, steroid use, type of colorectal resection, operating time, and method of wound closure. Differences in ASA class, wound classification, and preexisting comorbidities resolved when 80 open and 5 hand-assisted patients who underwent emergency resections were excluded from analysis. Rate of stoma creation remained higher in open patients even after excluding emergency cases (p < 0.01). Overall SSI rates following open and hand-assisted resections were 28 and 44 %, respectively (p = 0.015). Superficial SSI rates were higher in hand-assisted patients (20 vs. 40 %, p = 0.006). Deep (2.1 vs. 4 %, p = 0.605) and organ space SSI rates (5.1 vs. 0 %, p = 0.221) did not differ. These results did not change when emergency resections were excluded: overall 28 and 44 % (p = 0.015), superficial (23 vs. 44 %, p = 0.009), deep (3.5 vs. 4.4 %, p = 0.541), and organ space (7 vs. 0 %, p = 0.066). CONCLUSION: This study seems to suggest possibly higher rates of incisional SSI in patients who underwent hand-assisted colorectal resection as compared to open. This retrospective study had, however, insufficient power to stratify by surgeon and control for risk factors by logistic regression.

Dearterialization with mucopexy versus haemorrhoidectomy for grade III or IV haemorrhoids: short-term results of a double-blind randomized controlled trial.

AIM: There is scepticism regarding anatomical rationale and Doppler guidance for ligation of haemorrhoidal arteries. The null hypothesis of this randomized controlled trial (RCT) was that there is no difference in pain following dearterialization or haemorrhoidectomy for grade III/IV internal haemorrhoids in a minimum of three quadrants. METHOD: This was a single-centre, double-blind RCT. Patients were allocated to dearterialization or haemorrhoidectomy. Included haemorrhoids were grade III, prolapsing but reducible; and grade IV, chronic non-incarcerated. The primary end-point was pain. Patients with external component, acute incarcerated grade IV or recurrent haemorrhoids were not included. The interventions were dearterialization (with Doppler guidance and mucopexy) or haemorrhoidectomy. The main outcome measure was the Brief Pain Inventory (BPI). RESULTS: Twenty dearterialization patients were comparable to 20 haemorrhoidectomy patients for age (P = 0.107), body mass index (P = 0.559), race (P = 0.437), American Society of Anesthesiology score (P = 0.569), comorbidities (P = 0.592), grade (P = 0.096), quadrants (P = 0.222), Fecal Incontinence Quality-of-Life Score (FIQOL; P = 0.388), coping (P = 0.532), depression (P = 0.505), embarrassment (P = 0.842), and Short Form Health Survey (SF-12) physical components (P = 0.337), SF-12 mental components (P = 0.396) and constipation (P = 0.628) scores. Dearterialization patients had shorter operative time (36 vs 54 min, P = 0.043) with less pain (P = 0.011) and urinary retention (P = 0.012). Dearterialization patients had first bowel movement earlier (1.3 vs 4.6 days, P = 0.001), less pain (P = 0.011) and lower pain intensity (P = 0.001). Narcotic requirements were reduced in dearterialization patients (25% vs 100%, P = 0.001), with less medication (4.9 vs 112 pills, P = 0.001) and shorter regimen (0 vs 7 days, P = 0.001). BPI did not differ on days 1, 3, 5, 7 and 14 except for less pain in dearterialization patients. At 3 months, symptomatic relief was the same with no differences in BPI, FIQOL or SF-12. CONCLUSION: Compared with haemorrhoidectomy, dearterialization led to less pain in grade III/IV haemorrhoids.

The impact of high-dose methotrexate on intracellular 6-mercaptopurine disposition during interval therapy of childhood acute lymphoblastic leukemia.

PURPOSE: Low-dose methotrexate (MTX) therapy is the cornerstone treatment of acute lymphoblastic leukemia (ALL) and may enhance the activation of 6-mercaptopurine (6-MP) to 6-thioguanine nucleotides (6-TGN). Yet, data have established that high-dose MTX (HDMTX) hampers the accumulation of 6-TGN in red blood cells (RBC) and lymphoblasts. METHODS: To clarify the pharmacokinetic interactions between these two antimetabolites, we serially measured RBC 6-TGN and MTX polyglutamates (MTXPG) levels following repeated courses of HDMTX (5 g/m(2) over 24 h) with daily oral 6-MP (25 mg/m(2)) during interval therapy in 20 children with ALL. RESULTS: HDMTX produced a rapid reduction in RBC 6-TGN 24 h after the start of MTX, and this effect was sustained at least by the third day (median decrease -21%; P < 0.001). However, a return to pre-infusion of 6-TGN levels was observed by the time of the following HDMTX course 14 days later (P < 0.001). RBC MTX polyglutamates accumulation followed Michaelis-Menten kinetics but was not associated with the change in pre-infusion 6-TGN levels which remained stable during the interval period. CONCLUSION: HDMTX does not appear to enhance 6-MP activation to 6-TGN. Moreover, given that the deleterious effect of HDMTX on intracellular 6-MP disposition has been shown to be several folds greater in lymphoblasts than in RBC. Our data warrant additional studies elucidating the optimal MTX dose synergizing with 6-MP.

Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients.

The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine dosage regimens. Pharmacokinetic samples were collected from 50 de novo pediatric kidney transplant patients (age 2-18 years) who were on tacrolimus treatment. Population pharmacokinetic analysis of tacrolimus was performed using NONMEM, and the impact of variables (demographic and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested. The pharmacokinetic data were described by a two-compartment model that incorporated first-order absorption and lag time. The apparent oral clearance (CL/F) was significantly related to body weight (allometric scaling); in addition, it was higher in patients with low hematocrit levels and lower in patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model developed in de novo pediatric kidney transplant patients demonstrated that, in children, tacrolimus dosage should be based on weight, hematocrit levels, and CYP3A5 polymorphism. Individualization of therapy will enable the optimization of tacrolimus exposure, with resultant beneficial effects on kidney function in the initial post-transplantation period.

Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia?

BACKGROUND AND OBJECTIVE: The activity of thiopurine S-methyltransferase (TPMT), a key enzyme in the metabolism of purine analogues, displays wide inter-subject variability partly due to a genetic polymorphism. Previous studies have suggested adjusting purine analogues dosing according to TPMT activity but measurements are costly and time-consuming. It is still unclear, especially under treatment, whether the simpler TPMT genotyping reliably predicts enzyme activity. Our aim was to study the possible correlation of TPMT genotype with phenotype. METHODS: We determined the genotypic status and TMPT activity, at diagnosis and after 6 months of maintenance therapy, of 118 children with acute lymphoblastic leukaemia (ALL). RESULTS AND DISCUSSION: Eighty-nine per cent of the children had a homozygous wild-type genotype (group 1), 11% had one or two mutant allele(s) (group 2). At both time points, TPMT activity (U/mL peripheral red blood cell) was significantly higher in group 1 than in group 2 (P < 0.001) but inter-group levels overlapped considerably. There was considerable heterogeneity in the percentage increase in TPMT activity after therapy, and little correlation between metabolites ratio [6-methylmercaptopurine derivative/6-thioguanine nucleotides (6-TGN)] and TPMT activity at the end of 6 months' maintenance treatment. These results show that TPMT activity cannot be used as an accurate tool for 6-mercaptopurine monitoring. CONCLUSION: Genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity. ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites (6-TGN) and methylated metabolites.