Which tumour factors preclude organ preservation in patients with rectal cancer?

BACKGROUND: cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy. METHODS: A review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution. Of these, 17.9 % started w&w, 12.6 % achieved clinical complete response (cCR) and 9.0 % sustained cCR during median follow-up of 54 months. RESULTS: The multivariable logistic analysis showed that the proportion of circumferential bowel involvement and EMVI significantly influenced the chance of sustained cCR; odds ratios were 0.063 (95 % confidence interval [CI] 0.008-0.489, p = 0.008), and 0.109 (95 % CI 0.014-0.850, p = 0.034), respectively. Sustained cCR was observed in none of the 57 patients with 90 %-100 % circumferential bowel involvement and in only one of the 89 patients with EMVI. In contrast, cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes or MRF+ were not independently associated with sustained cCR. Among the subgroups of patients with these features but without (near-)circular tumour or EMVI+, sustained cCR was observed in 12 %-25 % of patients. CONCLUSION: Sustained cCR after routine preoperative radio(chemo)therapy is unlikely in patients with (near-)circular tumour or EMVI, whereas patients with cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes and MRF+ should not be denied w&w.

Decoding murine cytomegalovirus.

The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics approaches revealed HCMV gene expression to be substantially more complex comprising several hundred viral ORFs. Here, we provide a state-of-the art reannotation of lytic MCMV gene expression based on integrative analysis of a large set of omics data. Our data reveal 365 viral transcription start sites (TiSS) that give rise to 380 and 454 viral transcripts and ORFs, respectively. The latter include >200 small ORFs, some of which represented the most highly expressed viral gene products. By combining TiSS profiling with metabolic RNA labelling and chemical nucleotide conversion sequencing (dSLAM-seq), we provide a detailed picture of the expression kinetics of viral transcription. This not only resulted in the identification of a novel MCMV immediate early transcript encoding the m166.5 ORF, which we termed ie4, but also revealed a group of well-expressed viral transcripts that are induced later than canonical true late genes and contain an initiator element (Inr) but no TATA- or TATT-box in their core promoters. We show that viral upstream ORFs (uORFs) tune gene expression of longer viral ORFs expressed in cis at translational level. Finally, we identify a truncated isoform of the viral NK-cell immune evasin m145 arising from a viral TiSS downstream of the canonical m145 mRNA. Despite being ≈5-fold more abundantly expressed than the canonical m145 protein it was not required for downregulating the NK cell ligand, MULT-I. In summary, our work will pave the way for future mechanistic studies on previously unknown cytomegalovirus gene products in an important virus animal model.

The Effects of Protease Supplementation and Faba Bean Extrusion on Growth, Gastrointestinal Tract Physiology and Selected Blood Indices of Weaned Pigs.

The aim of the study was to investigate how the extrusion of faba bean seeds (var. Albus) and/or the addition of protease to pigs' diets affected the animals' growth parameters, digestibility of nutrients, selected physiological parameters of the digestive tract, and biochemical blood parameters. A 28-day experiment was conducted on 32 pigs weighing 9 ± 0.2 kg. The animals were allocated to four treatments in a 2 × 2 factorial arrangement with the main effects of extrusion (raw or extruded) and effects of protease supplementation (0 and 0.05%). Extrusion reduced the levels of neutral detergent fibre, trypsin inhibitor, phytate-P, and resistant starch but did not improve the digestibility of protein and dry matter in faba bean seeds. The pigs' growth performance, ileal digestibility, enzyme activity, and morphometric parameters of the ileum were not significantly affected by extrusion, except for a higher feed intake between the 15th and 28th day of the experiment. The protease supplementation gave comparable results as the diet without protease, except the feed conversion ratio (in the periods of 15-28th day and 0-28th day), which was higher than in the groups without protease. The extrusion and protease increased acetate and acetoacetate contents in the cecal digesta, but propionate, butyrate, and isovalerate concentrations in the digesta of the pigs in this group were lower. Thanks to protease supplementation, protein and oil levels in the diet were reduced, which cut the cost of feed mixtures. The extrusion and protease additive combined together did not improve the pigs' growth performance in this experiment.

Watch-and-wait strategy in rectal cancer: Is there a tumour size limit? Results from two pooled prospective studies.

BACKGROUND: Frequency and predictive factors for a clinical complete response (cCR) in unselected patients are unclear. MATERIAL AND METHODS: Two prospective observational studies were designed and pooled to explore predictive factors for cCR. Both studies evaluated the watch-and-wait strategy in consecutive patients; the first single-institutional study in elderly with a small tumour, the second multi-institutional study in all the patients receiving standard of care preoperative radiotherapy. RESULTS: Four hundred and ninety patients were analysed. Short-course radiotherapy alone, or with consolidation chemotherapy or chemoradiation was given to 40.6%, 40.2% and 19.2% of the patients, respectively. The median interval from the radiation start to the first tumour response assessment was 10.2 weeks for short-course radiation and 13.2 weeks for chemoradiation. Seventy-three patients had cCR and 71 underwent w&w with the median follow-up of 24 months. The regrowth rate was 26.8%. cCR rate was 39.0% for low-risk cancer (cT1-2N0), 16.8% for intermediate-risk (cT3 with unthreatened mesorectal fascia [MRF-] or cT2N+) and 5.4% for high-risk (cT4 or MRF+). In the multivariable analysis, tumour volume (or tumour length and circumferential extent) and cN status were significant predictors for cCR. In circular cancers or with a length ≥7 cm (n = 184), cCR rate was only 2.7%, sustained cCR 1.6% and the sensitivity of cCR diagnosis 23.1%. None of 27 patients with a tumour larger than 120 cm3 achieved cCR. CONCLUSIONS: Considering watch-and-wait strategy is questionable in patients with circular tumours or with tumour length ≥7 cm.

Clinical Reality and Treatment for Local Recurrence of Rectal Cancer: A Single-Center Retrospective Study.

Background and Objectives: Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Materials and Methods: Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Results: Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery (n = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery (n = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Conclusions: Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.

Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.

Herpes simplex virus 1 (HSV-1) induces a profound host shutoff during lytic infection. The virion host shutoff (vhs) protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8 h of lytic HSV-1 infection, we used transcriptome sequencing of total, newly transcribed (4sU-labeled) and chromatin-associated RNA in wild-type (WT) and Δvhs mutant infection of primary human fibroblasts. Following virus entry, vhs activity rapidly plateaued at an elimination rate of around 30% of cellular mRNAs per hour until 8 h postinfection (p.i.). In parallel, host transcriptional activity dropped to 10 to 20%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and Δvhs infections. Both induced strong transcriptional upregulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed vhs-nuclease-activity-dependent transcriptional downregulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a vhs-dependent reduction in protein levels by 8 h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8 h of lytic HSV-1 infection.IMPORTANCE The HSV-1 virion host shutoff (vhs) protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in vhs activity, as well as virus-induced global loss of host transcriptional activity, during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and Δvhs infections, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection, and identified vhs-dependent transcriptional downregulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to vhs-mediated mRNA degradation and resulted in a concordant loss in protein levels by 8 h p.i. for many of the respective genes.

A Comparison of the Composition and Contamination of Soybean Cultivated in Europe and Limitation of Raw Soy Seed Content in Weaned Pigs' Diets.

The aim of this study was to compare the chemical composition of European soy seeds. A mycological and toxigenic screening was carried out on 18 varieties of soy seeds harvested in Poland. Moreover, the level of soybean meal (SBM) substitution by raw soybean seeds was analysed in terms of its effect on young pigs' performance (body weight gain, feed intake, feed utilisation) along with apparent total tract digestibility (ATTD) of dry matter and crude protein in the diets. In a 28-day trial, 48 male pigs were tested using a marker method with TiO2. In their diets, SBM was replaced by soy seeds in the amounts of 0%, 5%, 10%, 15%, 20% and 25%. In the last 3 days of the experiment, samples of excreta from each animal separately were collected three times per day. The chemical composition of soybean seeds differed in terms of their contents of crude protein, ether extract, neutral detergent fibre and raffinose family oligosaccharides, as well as the trypsin inhibitor activity. Seeds were also contaminated with fungi, yeast and mycotoxins, mainly zearalenone and deoxynivalenol. The ATTD of crude protein ranged from 70.6% to 77.6% and that of dry matter from 93.5% to 94.6%, with no differences between the groups being found (p > 0.05). Pigs' performance parameters were reduced strongly with increasing amounts of raw seeds in the diets (p < 0.05). The results indicate that only a 5% addition of raw soy seeds in pigs' diet is recommended.

Growth performance and Carcass quality in broiler chickens fed on legume seeds and rapeseed meal.

The aim of this study was to compare the growth performance parameters, carcass quality, and meat traits in broiler chickens fed on diets containing legume seeds and rapeseed meal as an alternative to soybean meal. In this study, 448 male ROSS 308 chicks were divided into subgroups: a control group (I) fed on soybean meal (SBM), and six experimental groups II-rapeseed meal (RSM); III-white lupin (WY); IV-yellow lupin (YL); V-narrow-leaved lupin NLL; VI-pea (Pe); and VII-faba bean (FB). After 42 days of rearing, 10 birds from each group were slaughtered and dissected. The control group was characterized by better growth performance compared to the other groups. In addition, the European Broiler Index was lower in each experimental group compared to the SBM group. A lower dressing percentage was found only in the NLL group. The muscle content in birds from the RSM and FB groups was significantly higher than in the other groups, but the fat content was lower. Meat from SBM group was characterized by the highest protein content, but a reduced content of fat and water in the muscles. The most similar results were found between the control group and the FB group receiving a diet based on faba beans. Furthermore, lupins had a similar effect on the carcass traits when used in the diets. The quality of meat in broilers fed on faba beans with the addition of potato protein and brewers' yeast was similar to that of those fed on soybean meal, because the antinutrients were the lowest in faba bean seeds. Faba beans are proposed as a possible alternative source of protein in poultry diets. Other legume seeds should be analyzed in future studies.

Integrative functional genomics decodes herpes simplex virus 1.

The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution.

Quality and Physicochemical Traits of Carcasses and Meat from Geese Fed with Lupin-Rich Feed.

The aim of the study was to analyze the quality of geese meat receiving feed with soybean meal (group 1), yellow lupin (group 2), narrow-leaved lupin (group 3), or white lupin (group 4). In total, 400 male White Koluda® geese were randomly assigned to four groups, with 10 replicates and 10 birds each, during the 77-day rearing period. After the end of the rearing period, 10 birds from each group were slaughtered and dissected. Meat quality traits were measured. Based on the production results, it can be concluded that geese use fodder with yellow and white lupin to the same degree as in the case of the control group and higher body weight gain was recorded in the first rearing period. In contrast, the use of narrow-leaved lupin in mixtures for geese worsened the feed used. Meat traits were similar in all groups, including the content of muscles and fat in the carcass (p > 0.05), excluding abdominal fat. The weight of abdominal fat and its proportion in the carcass were higher (p < 0.05) in geese from group 4. A higher (p < 0.05) pH was found in group 1. The protein and intramuscular fat content in breast muscles was highest (p < 0.05) in geese from group 4, and a higher water content was found in group 1. The protein content in leg muscles was higher in group 3, and the fat content was higher in group 4 (p < 0.05). The color and water-holding capacity of meat were comparable in all groups (p > 0.05). The analysis revealed a positive effect of replacing soybean meal with alternative protein sources, especially yellow and white lupin, on the growth performance and quality of goose meat.

Effect of Dietary Protein Sources Substituting Soybean Meal on Growth Performance and Meat Quality in Ducks.

The study aimed to examine the growth performance and meat quality of Pekin ducks fed diets consisting of various protein source alternatives (groups: II-yellow lupin (YL) and rapeseed meal (RSM); III-YL and narrow-leaved lupin (NLL); IV-pea and YL; V-RSM, YL, NLL and pea) to (I) soybean meal (SBM) and RSM. Four hundred and twenty ducks were assigned to five groups with six replicates (14 birds per group). After 7 weeks, 10 ducks from each group were slaughtered. Breast muscles were analyzed for water-holding capacity, drip loss, color, and elasticity. Productivity parameters did not differ between groups I and II but were lower in V. The weight of carcass, neck with skin, skin with subcutaneous fat and total fat were highest in group II. The proportion of wings was higher in group V. In group II, lightness (L*) was higher, but redness (a*) was lower. In groups, I and III, L* was lower and a* was higher. Breast muscles contained more protein in groups I and II, more fat in groups I and III and more water in groups II and IV. The inclusion of vegetable protein alternatives to SBM in duck diets provided the best results in birds fed with YL and RSM (ratio of 1:0:31 in starter and 1:0.81 in grower).

Neoadjuvant chemotherapy with or without oxaliplatin after short-course radiotherapy in high-risk rectal cancer: A subgroup analysis from a prospective study.

AIM: To evaluate the role of oxaliplatin in neoadjuvant chemotherapy delivered after short-course irradiation. BACKGROUND: Using oxaliplatin in the above setting is uncertain. PATIENTS AND METHODS: A subgroup of 136 patients managed by short-course radiotherapy and 3 cycles of consolidation chemotherapy within the framework of a randomised study was included in this post-hoc analysis. Sixty-seven patients received FOLFOX4 (oxaliplatin group) while oxaliplatin was omitted in the second period of accrual in 69 patients because of protocol amendment (fluorouracil-only group). RESULTS: Grade 3+ acute toxicity from neoadjuvant treatment was observed in 30% of patients in the oxaliplatin group vs. 16% in the fluorouracil-only group (p = 0.053). The corresponding proportions of patients having radical surgery or achieving complete pathological response were 72% vs. 77% (odds ratio [OR] = 0.88; 95% confidence interval [CI]: 0.39-1.98; p = 0.75) and 15% vs. 7% (OR = 2.25; 95% CI: 0.83-6.94; p = 0.16), respectively. The long-term outcomes were similar in the two groups. Overall and disease-free survival rates at 5 years were 63% vs. 56% (p = 0.78) and 49% vs. 44% (p = 0.59), respectively. The corresponding numbers for cumulative incidence of local failure or distant metastases were 33% vs. 38% (hazard ratio [HR] = 0.89; 95% CI: 0.52-1.52; p = 0.68) and 33% vs. 33% (HR = 0.78; 95% CI: 0.43-1.40; p = 0.41), respectively. CONCLUSION: Our findings do not support adding oxaliplatin to three cycles of chemotherapy delivered after short-course irradiation.

Effects of feeding intact, ground and/or pelleted rapeseed on nutrient digestibility and growth performance of broiler chickens.

In this study, the effect of grinding or pelleting of rapeseed on the digestibility, apparent metabolisable energy (AMEN), growth performance and gizzard weight of broiler chickens was evaluated. In Exp. 1, four treatments were tested (240 broiler chickens, 20 replications, 3 birds per cage). Birds received either a basal diet or were fed with rapeseed of different sized particles (fine, medium and coarse ground, respectively). In Exp. 2, 10 treatments were assessed (360 chickens, 12 replications, 3 birds per cage), where five different diets (a basal diet and four diets with intact rapeseed, fine ground, medium ground or coarse ground rapeseed, respectively) were fed non-pelleted or pelleted. In Exp. 3, two treatments were compared (224 broiler chickens, 14 replications, 8 birds per floor pen): fine ground rapeseed (FG) and intact rapeseed (IS). Compared with medium and coarse ground rapeseed, fine grinding increased in Exp. 1 the AMEN of rapeseed and the precaecal digestibility (PD) of dry matter and ether extract (EE) (p < 0.05). In Exp. 2, the content of AMEN and the PD of EE and crude protein (CP) increased as the degree of grinding increased when diets were not pelleted (p < 0.01). In contrast, the significantly highest values for these parameters were measured after pelleting without effect of grinding, resulting in a significant interaction between pelleting and grinding (p < 0.001). In Exp. 3, performance of chickens was not affected by dietary treatments, but gizzard weight and the PD of CP were higher when IS were included in the diet (p < 0.05). The results suggested that fine grinding may be used to increase the feeding value of full-fat rapeseed for broiler chickens. Nevertheless, pelleting of diets with rapeseed seemed to be much more effective in the reduction of particle size than grinding.

Optimisation of robust singleplex and multiplex droplet digital PCR assays for high confidence mutation detection in circulating tumour DNA.

Liquid biopsies offer the potential to monitor cancer response and resistance to therapeutics in near real-time. However, the plasma cell free DNA (cfDNA) level can be low and the fraction of circulating tumour DNA (ctDNA) bearing a mutation - lower still. Detection of tumour-derived mutations in ctDNA is thus challenging and requires highly sensitive and specific assays. Droplet digital PCR (ddPCR) is a technique that enables exquisitely sensitive detection and quantification of DNA/RNA markers from very limiting clinical samples, including plasma. The Bio-Rad QX200 ddPCR system provides absolute quantitation of target DNA molecules using fluorescent dual-labelled probes. Critical to accurate sample analysis are validated assays that are highly specific, reproducible, and with known performance characteristics, especially with respect to false positives. We present a systematic approach to the development and optimisation of singleplex and multiplex ddPCR assays for the detection of point mutations with a focus on ensuring extremely low false positives whilst retaining high sensitivity. We also present a refined method to determine cfDNA extraction efficiency allowing for more accurate extrapolation of mutational levels in source samples. We have applied these approaches to successfully analyse many ctDNA samples from multiple clinical studies and generated exploratory data of high quality.

Quality improvement of OCT angiograms with elliptical directional filtering.

We present a method of OCT angiography (OCTA) data filtering for noise suppression and improved visualization of the retinal vascular networks in en face projection images. In our approach, we use a set of filters applied in three orthogonal axes in the three-dimensional (3-D) data sets. Minimization of artifacts generated in B-scan-wise data processing is accomplished by filtering the cross-sections along the slow scanning axis. A-scans are de-noised by axial filtering. The core of the method is the application of directional filtering to the C-scans, i.e. one-pixel thick sections of the 3-D data set, perpendicular to the direction of the scanning OCT beam. The method uses a concept of structuring, directional kernels of shapes matching the geometry of the image features. We use rotating ellipses to find the most likely local orientation of the vessels and use the best matching ellipses for median filtering of the C-scans. We demonstrate our approach in the imaging of a normal human eye with laboratory-grade spectral-domain OCT setup. The "field performance" is demonstrated in imaging of diabetic retinopathy cases with a commercial OCT device. The absolute complex differences method is used for the generation of OCTA images from the data collected in the most noise-wise unfavorable OCTA scanning regime-two frame scanning.

Exome scale map of genetic alterations promoting metastasis in colorectal cancer.

BACKGROUND: Approximately 90% of colorectal cancer (CRC) deaths are caused by tumors ability to migrate into the adjacent tissues and metastase into distant organs. More than 40 genes have been causally linked to the development of CRC but no mutations have been associated with metastasis yet. To identify molecular basis of CRC metastasis we performed whole-exome and genome-scale transcriptome sequencing of 7 liver metastases along with their matched primary tumours and normal tissue. Multiple, spatially separated fragments of primary tumours were analyzed in each case. Uniformly malignant tissue specimen were selected with macrodissection, for three samples followed with laser microdissection. RESULTS: > 100 sequencing coverage allowed for detection of genetic alterations in subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT, previously associated with CRC development, were detected in most patients. Several new associations were identified, including PLXND1, CELSR3, BAHD1 and PNPLA6. CONCLUSIONS: We confirm the essential role of inflammation in CRC progression but question the mechanism of matrix metalloproteinases activation described in other work. Comprehensive sequencing data made it possible to associate genome-scale mutation distribution with gene expression patterns. To our knowledge, this is the first work to report such link in CRC metastasis context.

Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study.

BACKGROUND AND PURPOSE: It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. MATERIAL AND METHODS: In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. RESULTS: Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. CONCLUSIONS: This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate.

The Assessment of Clinical Usage and Prognostic Value of YKL-40 Serum Levels in Patients With Rectal Cancer Without Distant Metastasis.

BACKGROUND: Colorectal cancer is one of the most common and significant malignancies in the world. YKL-40 (chitinase-3-like protein 1) is involved in cell proliferation, migration, inflammation, and tissue remodeling; and serum levels of YKL-40 are associated with patient outcome in various cancers. The aim of this study was to assess the potential clinical usage of YKL-40 pretreatment serum levels as a prognostic biomarker in rectal cancer. METHODS: Concentrations of YKL-40 and standard tumor marker-Carcinoembryonic antigen (CEA)-were assessed in serum of 83 patients with rectal cancer without distant metastasis, and association with clinicopathological characteristics and disease-free and overall survival was evaluated. RESULTS: Concentration of YKL-40 was significantly higher in serum of patients with rectal cancer compared to healthy controls ( P = .0001), and YKL-40 levels were able to predict rectal cancer (area under the Receiver Operating Characteristic [ROC] curve = .769) with higher accuracy than CEA (area under the ROC curve = .728) in patients with early stage disease. Increased YKL-40 levels were significantly associated with age ( P = .001); however, no association with other clinicopathological characteristics was observed. Finally, in patients with recurrence, the percentage of cases with increased concentration of YKL-40 was significantly higher than in patients without recurrence ( P = .041), and Kaplan-Meier analysis demonstrated that elevated YKL-40 concentration is a predictor of poor overall survival in patients with rectal cancer. CONCLUSION: Pretreatment serum levels of YKL-40 may be a novel prognostic factor of overall and disease-free survival in patients with nonmetastatic colorectal cancer.