Incisional hernia following colorectal cancer surgery according to suture technique: Hughes Abdominal Repair Randomized Trial (HART).

BACKGROUND: Incisional hernias cause morbidity and may require further surgery. HART (Hughes Abdominal Repair Trial) assessed the effect of an alternative suture method on the incidence of incisional hernia following colorectal cancer surgery. METHODS: A pragmatic multicentre single-blind RCT allocated patients undergoing midline incision for colorectal cancer to either Hughes closure (double far-near-near-far sutures of 1 nylon suture at 2-cm intervals along the fascia combined with conventional mass closure) or the surgeon's standard closure. The primary outcome was the incidence of incisional hernia at 1 year assessed by clinical examination. An intention-to-treat analysis was performed. RESULTS: Between August 2014 and February 2018, 802 patients were randomized to either Hughes closure (401) or the standard mass closure group (401). At 1 year after surgery, 672 patients (83.7 per cent) were included in the primary outcome analysis; 50 of 339 patients (14.8 per cent) in the Hughes group and 57 of 333 (17.1 per cent) in the standard closure group had incisional hernia (OR 0.84, 95 per cent c.i. 0.55 to 1.27; P = 0.402). At 2 years, 78 patients (28.7 per cent) in the Hughes repair group and 84 (31.8 per cent) in the standard closure group had incisional hernia (OR 0.86, 0.59 to 1.25; P = 0.429). Adverse events were similar in the two groups, apart from the rate of surgical-site infection, which was higher in the Hughes group (13.2 versus 7.7 per cent; OR 1.82, 1.14 to 2.91; P = 0.011). CONCLUSION: The incidence of incisional hernia after colorectal cancer surgery is high. There was no statistical difference in incidence between Hughes closure and mass closure at 1 or 2 years. REGISTRATION NUMBER: ISRCTN25616490 (http://www.controlled-trials.com)

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Analysis of phycotoxins in hand-picked plankton cells by micro-column liquid chromatography-tandem mass spectrometry

NRC publication: Ye

Analysis of phycotoxins in hand-picked plankton cells by micro-column liquid chromatography-tandem mass spectrometry

NRC publication: Ye

Certified reference materials for diarrhetic shellfish poisoning toxins

Reference materials play a very important role in analytical laboratories. They are used for calibration of instruments, development and validation of measurement methods, and routine assessment of method performance. Certified reference materials (CRMs) are essential for laboratories maintaining a quality system such as ISO-17025 because they ensure accuracy and traceability to international standards. The NRC-IMB Certified Reference Materials Program (CRMP) produces CRMs for shellfish toxins and distributes them on a not-for-profit basis. Diarrhetic shellfish poisoning (DSP) is a gastrointestinal illness caused by ingestion of shellfish contaminated with toxins produced by certain species of dinoflagellates. The principal toxins associated with DSP are okadaic acid (OA) and the dinophysistoxins, DTX1 and DTX2. The most common methods of analysis for these toxins are based upon liquid chromatography with either mass spectrometric (LC-MS) or fluorescence detection (LC-FLD). Accurate calibration is an essential step in such analyses, particularly for regulatory work. Two CRMs for DSP toxins are currently available from CRMP: (a) CRM-OA-b, a certified calibration solution for OA; and (b) CRM-DSP-Mus-b, a certified mussel tissue CRM for OA and dinophysistoxin-1. Two other calibration solution CRMs are in preparation for DTX1 and DTX2. OA, isolated from Prorocentrum lima, was carefully assessed for its purity by LC-MS and nuclear magnetic resonance (NMR). An exhaustive study of OA stability was performed in various solvents and under different conditions. Based on this work, methanol was selected as the best solvent. NMR was then used to measure the absolute concentration of OA in a CD3OH stock solution, which was then diluted very accurately in degassed, high purity methanol to a concentration of 20 \uc2\ub5mol L-1. Aliquots were dispensed into argon-filled glass ampoules, which were immediately flame-sealed. The mussel tissue CRM was produced by blending blue mussel (Mytilus edulis) digestive glands with a small amount of P. lima. The CRM (~4 grams of homogenate) is distributed in polypropylene bottles that were heat sealed, thermally sterilized and individually packed in trilaminate pouches. The toxin levels in this CRM were determined to be 10.1 mg/kg for OA and 1.3 mg/kg for DTX1 using LC-MS and LC-FLD after derivatization with 9-anthryldiazomethane (ADAM).NRC publication: Ye

Spirolides: Discovery, toxicity and pharmacological potential

NRC publication: Ye

The hunt for red tide toxins: New toxins, new analytical technologies

NRC publication: Ye

The characterization of two new spirolides isolated from Danish strains of the toxigenic dinoflagellate Alexandrium ostenfeldii.

Peer reviewed: YesNRC publication: Ye