Population-based study of surgical treatment with and without tumour resection in patients with locally recurrent rectal cancer.

BACKGROUND: Population-based studies of treatment of locally recurrent rectal cancer (LRRC) are lacking. The aim was to investigate the surgical treatment of patients with LRRC at a national population-based level. METHODS: All patients undergoing abdominal resection for primary rectal cancer between 1995 and 2002 in Sweden with LRRC as a first event were included. Detailed information about treatment, complications and outcomes was collected from the medical records. The patients were analysed in three groups: patients who had resection of the LRRC, those treated without tumour resection and patients who received best supportive care only. RESULTS: In all, 426 patients were included in the study. Of these, 149 (35·0 per cent) underwent tumour resection, 193 (45·3 per cent) had treatment without tumour resection and 84 (19·7 per cent) received best supportive care. Abdominoperineal resection was the most frequent surgical procedure, performed in 65 patients (43·6 per cent of those who had tumour resection). Thirteen patients had total pelvic exenteration. In total, 63·8 per cent of those whose tumour was resected had potentially curative surgery. After tumour resection, 62 patients (41·6 per cent) had a complication within 30 days. Patients who received surgical treatment without tumour resection had a lower complication rate but a significantly higher 30-day mortality rate than those who underwent tumour resection (10 versus 1·3 per cent respectively; P = 0·002). Of all patients included in the study, 22·3 per cent had potentially curative treatment and the 3-year survival rate for these patients was 56 per cent. CONCLUSION: LRRC is a serious condition with overall poor outcome. Patients undergoing curative surgery have an acceptable survival rate but substantial morbidity. There is room for improvement in the management of patients with LRRC.

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-ß3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.

Risk factors for anastomotic leakage following ileosigmoid or ileorectal anastomosis.

AIM: Reconstruction with an ileosigmoidal anastomosis (ISA) or ileorectal anastomosis (IRA) is a surgical option after a subtotal colectomy. Anastomotic leakage (AL) is a problematic complication and high rates have been reported, but there is limited understanding of the risk factors involved. The aim of this study was to assess the established and potential predictors of AL following ISA and IRA. METHOD: This was a retrospective cohort study including all patients who had undergone ISA or IRA at three Swedish referral centres for colorectal surgery between January 2007 and March 2015. Data regarding clinical characteristics, treatment and outcome were collected from medical records. Univariate and multivariate logistic regression models were used to determine the association between patient and treatment related factors and the cumulative incidence of AL. RESULTS: In total, 227 patients were included. Overall, AL was detected amongst 30 patients (13.2%). Amongst patients undergoing colectomy with synchronous ISA or IRA (one-stage procedure), AL occurred in 23 out of 120 (19.2%) compared with seven out of 107 (6.5%) after stoma reversal with ISA or IRA (two-stage procedure) (P = 0.004). In addition, the multivariate analyses revealed a statistically significantly lower odds ratio for AL following a two-stage procedure (OR 0.10, 95% CI 0.03-0.41, P = 0.001). CONCLUSIONS: This study confirms high rates of AL following ISA and IRA. In particular, a synchronous procedure with colectomy and ISA/IRA carries a high risk of AL.

Preoperative CT-based predictive factors for resectability and medium-term overall survival in patients with peritoneal carcinomatosis from colorectal cancer.

AIM: To determine preoperative radiological findings that may correlate with resectability and medium-term overall survival (OS) in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC). MATERIALS AND METHODS: The study included 81 consecutive patients with PC scheduled for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). PCI scores from preoperative computed tomography (CT) were compared with Peritoneal Cancer Index (PCI) scores at laparotomy. Odds ratio (OR), a Cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed to evaluate resectability ("open and close procedure" [O&C]) and OS. RESULTS: A radiological PCI score ≥20 (OR; 20.61 p=0.001), involvement of the perihepatic region (OR; 3.63, p=0.047) and extensive small bowel involvement (OR; 9.90, p=0.019) were risk factors for O&C. Involvement of the left abdominal region correlated adversely to OS (HR; 6.86, p<0.001). CONCLUSIONS: The location of PC, in addition to the extent of PC as determined by preoperative CT, predicts resectability and medium-term survival.

Non-native plants add to the British flora without negative consequences for native diversity.

Plants are commonly listed as invasive species, presuming that they cause harm at both global and regional scales. Approximately 40% of all species listed as invasive within Britain are plants. However, invasive plants are rarely linked to the national or global extinction of native plant species. The possible explanation is that competitive exclusion takes place slowly and that invasive plants will eventually eliminate native species (the "time-to-exclusion hypothesis"). Using the extensive British Countryside Survey Data, we find that changes to plant occurrence and cover between 1990 and 2007 at 479 British sites do not differ between native and non-native plant species. More than 80% of the plant species that are widespread enough to be sampled are native species; hence, total cover changes have been dominated by native species (total cover increases by native species are more than nine times greater than those by non-native species). This implies that factors other than plant "invasions" are the key drivers of vegetation change. We also find that the diversity of native species is increasing in locations where the diversity of non-native species is increasing, suggesting that high diversities of native and non-native plant species are compatible with one another. We reject the time-to-exclusion hypothesis as the reason why extinctions have not been observed and suggest that non-native plant species are not a threat to floral diversity in Britain. Further research is needed in island-like environments, but we question whether it is appropriate that more than three-quarters of taxa listed globally as invasive species are plants.

Population-based study of factors predicting treatment intention in patients with locally recurrent rectal cancer.

BACKGROUND: Local recurrence of rectal cancer (LRRC) is associated with poor survival unless curative treatment is performed. The aim of this study was to investigate predictive factors for treatment with curative intent in patients with LRRC. METHODS: Population-based data for patients treated for primary rectal cancer between 1995 and 2002, and with LRRC reported as first event were collected from the Swedish Colorectal Cancer Registry and medical records. The associations between patient-, primary tumour- and LRRC-related factors and intention of the treatment for LRRC were determined. The impact of the identified predictive factors on prognosis after treatment with curative intent was also assessed. RESULTS: A total of 426 patients were included in the study, of whom 149 (35·0 per cent) received treatment with curative intent. Factors significantly associated with treatment of the LRRC with palliative intent were primary surgery with abdominoperineal resection (odds ratio (OR) 5·16, 95 per cent c.i. 2·97 to 8·97), age at diagnosis of LRRC at least 80 years (OR 4·82, 2·37 to 9·80), symptoms at diagnosis (OR 2·79, 1·56 to 5·01) and non-central location of the LRRC (OR 1·79, 1·15 to 2·79). The overall 5-year survival rate was 8·9 per cent for all patients and 23·1 per cent among those treated with curative intent. In patients treated with curative intent, factors associated with increased risk of death were age 80 years or more (hazard ratio (HR) 2·44, 95 per cent c.i. 1·55 to 3·86), presence of symptoms (HR 1·92, 1·20 to 3·05), non-central tumour location (HR 1·51, 1·01 to 2·26) and presence of hydronephrosis (HR 2·02, 1·18 to 3·44). CONCLUSION: Non-central location of the LRRC, presence of symptoms and age at least 80 years at diagnosis of the LRRC were associated with treatment with palliative intent.

Distinct expression of interleukin (IL)-36α, ß and γ, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease.

Interleukin (IL)-36α, IL-36ß and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36ß and IL-38 mRNA, was induced and correlated with IL-1ß and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, ß, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1ß, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1ß and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68⁺ macrophages, dendritic/Langerhans cells and CD79α⁺ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36ß and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.

Versatile optical laser system for experiments at the European X-ray free-electron laser facility.

We present the main features of the final prototype of a pulsed optical laser, developed for pump-probe and other experiments in conjunction with the femtosecond x-ray beams at the European X-ray free-electron laser facility. Adapted to the temporal x-ray emission pattern of the facility, the laser provides 10 Hz bursts of up to 600 µs duration with intra-burst pulse frequencies as high as 4.5 MHz. In this mode, we have generated pulses as short as 12 fs at 350 W average power during the burst and with beam qualities close to the diffraction limit. This is, to the best of our knowledge, the highest power to date of a few-cycle laser operating at a center wavelength of 800 nm. Important for experimental flexibility, the laser can be configured in various unique ways, enabling, e.g., energy scaling to >3 mJ per pulse through a frequency change down to 100 kHz and the generation of nearly transform limited pulses between 12 fs and 300 fs. In addition to the 800 nm femtosecond beam line, a synchronized long pulse (0.8 ps or 400 ps) 1030 nm beam can be utilized, offering up to 4 kW burst average power, i.e. up to 40 mJ per pulse at 100 kHz. Efficient nonlinear wavelength conversion and tuning through intrinsic and external means further enhance the capabilities of the laser.

High power burst-mode optical parametric amplifier with arbitrary pulse selection.

We present results from a unique burst-mode femtosecond non-collinear optical parametric amplifier (NOPA) under development for the optical - x-ray pump-probe experiments at the European X-Ray Free-Electron Laser Facility. The NOPA operates at a burst rate of 10 Hz, a duty cycle of 2.5% and an intra-burst repetition rate of up to 4.5 MHz, producing high fidelity 15 fs pulses at a center wavelength of 810 nm. Using dispersive amplification filtering of the super-continuum seed pulses allows for selectable pulse duration up to 75 fs, combined with a tuning range in excess of 100 nm whilst remaining nearly transform limited. At an intra-burst rate of 188 kHz the single pulse energy from two sequential NOPA stages reached 180 µJ, corresponding to an average power of 34W during the burst. Acousto- and electro-optic switching techniques enable the generation of transient free bursts of required length and the selection of arbitrary pulse sequences inside the burst.

Local control and survival after extralevator abdominoperineal excision for locally advanced or low rectal cancer.

AIM: Conventional, synchronous combined, abdominoperineal excision (APE) for low rectal cancer is associated with intra-operative tumour perforation and tumour involvement of the circumferential resection margin (CRM+). Several studies have demonstrated worse rates of local recurrence and survival after APE than after low anterior resection (LAR). Extralevator APE (ELAPE) in the prone position may reduce the risk of perforation and involvement of resection margins and may therefore improve outcome. The aim of this study was to report the outcome after the introduction of ELAPE in a prospective study of consecutive patients from a single colorectal unit. METHOD: Between January 2000 and March 2013, 193 patients with low rectal cancer were treated with ELAPE at the Karolinska University Hospital, Stockholm, Sweden. All patients were recorded in the regional rectal cancer quality registry, where data on treatment and follow-up are prospectively reported. RESULTS: Preoperative staging with MRI assessed the tumour to be locally advanced (mrT4) in 126 (65%) of the 193 patients. The median tumour level above the anal verge was 3 cm. Intra-operative perforation occurred in 19 patients (10%) and histopathology revealed a positive CRM in 39 patients (20%). Until August 2013 [median follow-up 31 (0-156) months] local recurrence was detected in 12 patients. Five-year cancer specific survival was estimated to 68%. CONCLUSION: Good local control and survival may be achieved with ELAPE in patients with low, advanced rectal cancer.

Application of PERALS™ alpha spectrometry and gamma spectrometry for analysis and investigation of environmental spills at ISL uranium mining projects.

Radiation protection and environmental monitoring in mining requires effective and reliable radionuclide analysis at all stages of the mine project-prior to mining, during operation and through to remediation and decommissioning. The approach presented in this paper was specially developed for the monitoring of radioactive waste resulting from spills during mining and mineral processing operations and uses a combination of high resolution gamma spectrometry, and PERALS™ alpha spectrometry to identify and reliably quantify the activity of the major members of the U-238 decay chain at activities down to 10 mBq g(-1) by direct radionuclide counting and by assessment of the activity of their decay products. This approach has reduced sample preparation and analysis time while providing effective analysis and quantification of naturally occurring radionuclides in environmental samples. It has been successfully applied to several in situ leach (ISL) mining-related projects involving investigations of process material spill impacts and also to routine environmental monitoring.

Informal sale of antibiotics in Guatemalan convenience stores before and after implementation of federal antibiotic dispensing legislation.

BACKGROUND: Convenience stores in Guatemala provide essential consumer goods in communities, but many dispense antibiotics illegally. Federal legislation, passed in August of 2019, requires prescriptions for antibiotic purchase at pharmacies but it is unclear if this legislation is enforced or if it has any impact on unlawful sales of antibiotics. METHODS: To determine if antibiotic availability changed in convenience stores, we carried out a repeated measures study collecting antibiotic availability data before and after implementation of the dispensing regulation. RESULTS: There was no statistical difference in the proportion of convenience stores that sold antibiotics before and after antibiotic regulations [66.6% (295/443) and 66.7% (323/484), respectively, P>0.96], nor in the number of stores selling amoxicillin [55.5% (246/443) and 52.3% (253/484), respectively, P>0.96], but fewer stores (20%) sold tetracycline capsules after regulation was passed (P<0.05). For stores visited both before and after passage of legislation (n=157), 15% stopped selling antibiotics while 25% started selling antibiotics. Antibiotics from convenience stores were reportedly sold for use in people and animals. CONCLUSIONS: Antibiotics remain widely available in convenience stores consistent with no significant change in the informal sector after implementation of prescription requirements for pharmacies. Importantly, effects from regulatory change could have been masked by potential changes in antibiotic use during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic.

Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies.

OBJECTIVE: Targeted next generation sequencing (NGS) was evaluated for its ability to identify unanticipated targetable genomic alterations (GA) for patients with relapsed ovarian epithelial carcinoma (OC). METHODS: DNA sequencing was performed for 3320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries using DNA isolated from FFPE sections from 48 histologically verified relapsed OC specimens. The original primary tumor was sequenced in 26 (54%) of the cases and recurrent/metastatic tumor site biopsies were sequenced in 22 (46%) of the cases. Actionability was defined as: GA that predict sensitivity or resistance to approved or standard therapies or are inclusion or exclusion criteria for specific experimental therapies in NCI registered clinical trials. RESULTS: There were 38 (80%) serous, 5 (10%) endometrioid, 3 (6%) clear cell, 1 mucinous (2%) and 1 (2%) undifferentiated carcinomas. 141 GA were identified with an average of 2.9 GA (range 0-8) per tumor, of which 67 were actionable for an average of 1.4 actionable GA per patient (range 0-5). 33/48 (69%) of OC patient samples harbored at least one actionable GA. Most common GA were TP53 (79%); MYC (25%); BRCA1/2 (23%); KRAS (16.6%) and NF1 (14.5%). One tumor featured an ERBB2 point mutation. One of 3 (33%) of clear cell tumors featured cMET amplification validated by both FISH and IHC. CONCLUSIONS: NGS assessment of therapy resistant OC identifies an unexpectedly high frequency of GA that could influence targeted therapy selection for the disease.

High power ultra-widely tuneable femtosecond pulses from a non-collinear optical parametric oscillator (NOPO).

We present an ultra-widely tunable non-collinear optical parametric oscillator with an average output power of more than 3 W and a repetition frequency of 34 MHz. The system is pumped by the second harmonic of a femtosecond Yb:KLu(WO4)2 thin-disk laser oscillator. The wavelength of the signal pulse can be rapidly tuned over a wide range from the visible to the NIR just by scanning the resonator length.

Defunctioning stoma in rectal cancer surgery - A risk factor for Low Anterior Resection Syndrome?

BACKGROUND: In rectal cancer surgery the formation of a defunctioning stoma is common in order to reduce the consequences of an anastomotic leakage. The role of a defunctioning stoma and time to stoma reversal, in relation to major Low Anterior Resection Syndrome (LARS) in the long-term perspective, is still unclear. The aim of the study was to investigate the association between a defunctioning stoma and long-term bowel function. METHOD: Patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm county, Sweden, who had no history of anastomotic leakage, without a remaining stoma, free of cancer and alive in April 2017 were eligible for the study. The exposures were (i) use of defunctioning stoma at cancer surgery and (ii) time to stoma reversal. Main outcome was major LARS with information retrieved from the LARS score questionnaire. Multivariable logistic regression model was used to calculate odds ratios (OR) primary comparing major LARS to no LARS. RESULTS: A total of 430 patients were included in analysis. The mean follow-up time was 6.7 years after surgery (range 3.4-10.7 years). The use of a defunctioning stoma was associated to major LARS with an adjusted OR of 2.43 (95% CI 1.14-5.20) when compared to no stoma. There were no evident associations between time to stoma reversal and the risk of major LARS. CONCLUSION: This study indicates that the presence of a defunctioning stoma is associated with impaired bowel function in the long-term perspective, while failing to show any clear association to time to stoma reversal.

Glatiramer acetate (GA), the immunomodulatory drug, inhibits inflammatory mediators and collagen degradation in osteoarthritis (OA) cartilage.

OBJECTIVE: Glatiramer acetate (GA), the generic name for Copaxone, an immunomodulatory agent, has been shown to induce interleukin-1 receptor antagonist (IL-1Ra) production in macrophages. We therefore tested the effects of GA on the catabolic activities of osteoarthritis (OA) chondrocytes. DESIGN: Primary human chondrocytes and OA cartilage explants were utilized in this study. IL-1Ra, pro-matrix metalloproteinase-13 (proMMP-13) and prostaglandin E(2) (PGE(2)) were estimated in the cell culture supernatants and in vitro MMP-13 activity was measured using fluorogenic substrate. TaqMan Real-Time quantitative polymerase chain reaction (RT-qPCR) was performed to estimate relative expression levels of genes. RESULTS: GA treatment significantly increased transcription and production of sIL-1Ra (P=0.001) in both culture models. Furthermore, addition of GA (100 µg) inhibited: (1) spontaneous collagen degradation as assayed by CTX II enzyme-linked immunosorbent assay (ELISA) [mean CTX II (ng/g cartilage)] in control was 7.79 [95% confidence interval (CI) 2.57-13.02]-3.415 (95% CI 0.81-6.02) (P=0.0286); (2) spontaneous proMMP-13 secretion [mean MMP-13 (ng/g cartilage)] in control was 16.98 (95% CI 7.739-26.23)-6.973 (95% CI 1.632-12.31) (P=0.0286); (3) production of IL-1ß-induced inflammatory mediators such as nitric oxide (NO) [mean NO (µM)] in IL-1 cultures was 11.47 (95% CI 7.10-15.83)-0.87 (95% CI 0.18-1.56) (P=0.0022); and (4) recombinant MMP-13 in vitro activity (15-25%; P=0.004). CONCLUSIONS: These data suggest that GA effects may be due to upregulation of IL-1Ra as well as direct inhibition of MMP-13 activity. Based on these studies, we propose that GA has potential for disease modifying properties in OA and should be evaluated in vivo in animal studies.

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling.

The aim of the present study was to investigate the potential role of the recently discovered IL-1 family member IL-33 in bone remodeling. Our results indicate that IL-33 mRNA is expressed in osteocytes in non-inflammatory human bone. Moreover, IL-33 levels are increased by TNF-α and IL-1ß in human bone marrow stromal cells, osteoblasts and adipocytes obtained from three healthy donors. Experiments with the inhibitor GW-9662 suggested that expression of IL-33, in contrast to that of IL-1ß, is not repressed by PPARγ likely explaining why IL-33, but not IL-1ß, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1ß in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1ß, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and IL-33 and TNF-α/IL-1ß similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.

Preoperative tumour staging with multidisciplinary team assessment improves the outcome in locally advanced primary rectal cancer.

AIM: Multidisciplinary team meetings have been introduced as a result of developments in preoperative radiological tumour staging and neoadjuvant treatment. Multidisciplinary team recommendations will influence treatment decisions but their effect on patient outcome is unknown. The aim of this study was to assess outcome in relation to preoperative local and distant staging, with or without multidisciplinary team assessment. METHODS: A population-based registry of all patients with rectal cancer, treated in the Stockholm region from 1995 to 2004, identified 303 patients with locally advanced primary rectal cancer. The patients were classified into three groups: group 1, preoperative local and distant radiological tumour staging with discussion at a multidisciplinary team meeting; group 2, preoperative staging but no multidisciplinary team assessment; and group 3, no proper preoperative radiological staging. RESULTS: Neoadjuvant treatment was more prevalent in groups 1 and 2 than in group 3. The incidence of R0 resection differed significantly between the groups (52% in group 1, 43% in group 2 and 21% in group 3; P < 0.001). Local tumour control was achieved in 57%, 36%, and 19% of patients in groups 1, 2 and 3, respectively (P < 0.001). The estimated overall 5-year survival of patients was 30%, 28% and 12% in groups 1, 2 and 3, respectively. CONCLUSION: Preoperative radiological tumour staging in patients with locally advanced primary rectal cancer and discussion at a multidisciplinary team meeting increases the proportion of patients receiving neoadjuvant treatment and cancer-specific end-points.

Effect of root canal irrigant (sodium hypochlorite & saline) delivery at different temperatures and durations on pre-load and cyclic-loading surface-strain of anatomically different premolars.

AIM: To evaluate the effect of NaOCl (5%) and saline (control) irrigant delivery at different temperatures and durations on pre-load and cyclic-loading tooth-surface-strain (TSS) on anatomically different premolars. METHODOLOGY: Single-rooted premolars (n = 36), root-canal-prepared in standard manner, were randomly allocated to six irrigation groups: (A1) NaOCl-21 °C; (A2) NaOCl-60 °C; (A3) saline-21 °C then NaOCl-21 °C; (A4) saline-60 °C then NaOCl-21 °C; (A5) saline-21 °C then NaOCl-60 °C; (A6) saline-60 °C then NaOCl-60 °C. A1-2 received nine 10-min irrigation periods (IP) with NaOCl; A3-6 received nine 10-min IP with saline, followed by 9 IP with NaOCl at different temperature combinations. Premolars (n = 56) with single, fused or double roots prepared by standard protocol, were stratified and randomly allocated to: (B1) saline-21 °C; (B2) saline-80 °C; (B3) NaOCl-21 °C; (B4) NaOCl-80 °C. TSS (µÑ”) was recorded pre-irrigation, post-irrigation and pre-load for each IP and during cyclic loading 2 min after each IP, over 30-274 min, using strain-gauges. Generalised linear mixed models were used for analysis. RESULTS: Baseline TSS in double-rooted premolars was significantly (p=0.001) lower than in single/fused-rooted-premolars; and affected by mesial-wall-thickness (p=0.005). There was significant increase in loading-TSS (µÑ”) after NaOCl-21 °C irrigation (p=0.01) but decrease after NaOCl-60 °C irrigation (p=0.001). TSS also increased significantly (p = 0.005) after Saline-80 °C irrigation. Pre-load "strain-shift" was noted only upon first saline delivery but every-time with NaOCl. Strain-shift negatively influenced loading-TSS after saline or NaOCl irrigation (A3-6) but was only significant for saline-21 °C. CONCLUSIONS: Tooth anatomy significantly affected its strain characteristics, exhibiting limits within which strain changes occurred. Intra-canal introduction of saline or NaOCl caused non-random strain shifts without loading. Irrigation with NaOCl-21 °C increased loading tooth strain, as did saline-80 °C or NaOCl-80 °C but NaOCl-60 °C decreased it. A "chain-link" model was proposed to explain the findings and tooth biomechanics.