An international observational study assessing conservative management in hemorrhoidal disease: results of CHORALIS (aCute HemORrhoidal disease evALuation International Study).

Aim: Real-world evidence on the management of hemorrhoidal disease (HD) is limited. This international study collected clinical practice data on the effectiveness of conservative treatments for acute HD on symptoms and quality of life (QoL), providing perspectives of treatment modalities from different continents. Patients & methods: The 4-week observational prospective CHORALIS study involved adult outpatients consulting for spontaneous complaints of hemorrhoids (graded using Goligher classification) and prescribed conservative treatments according to usual clinical practice. Assessments were: anal pain/discomfort (visual analog scale [VAS]), other signs/symptoms (patient questionnaire), Patient Global Impression of Change (PGI-C) questionnaire and disease-specific QoL (HEMO-FISS-QoL questionnaire). Results: Of 3592 participants, 3505 were analyzed (58.4% male; age 40.5 ± 13.7 years; history of HD in 48.4%; 72.1% Goligher grade I and II). Pain and discomfort were the most common symptoms. Most treatments were venoactive drugs (VADs; 90.9%), particularly micronized purified flavonoid fraction (MPFF; 73.7%) and diosmin (14.6%). All VAD-based therapies improved signs/symptoms (number/intensity/frequency of pain, discomfort, bleeding, swelling, itching and soiling) and QoL. MPFF was associated with a significantly greater proportion of patients with no symptoms (48.8 vs diosmin 34.4%, p < 0.001), pain disappearance (69.7 vs diosmin 52.8%, p < 0.001), treatment impact at 1 week rated on PGI-C as 'very much better' (30.5 vs diosmin 17.9%, p < 0.001) and shorter times to improvement (mean ± SD 3.9 ± 1.5 days vs diosmin 4.2 ± 1.7 days). Conclusion: In this prospective real-world study of patients with acute HD, conservative therapies consisting mainly of VADs, including MPFF, improved the clinical signs and symptoms of disease, as well as QoL. This study evidence supports clinical advantages associated with VADs, mostly MPFF, for effectively managing acute HD.

Intraoperative fluorescence angiography as an independent factor of anastomotic leakage and a nomogram for predicting leak for colorectal anastomoses.

PURPOSE: Colorectal anastomotic leakage (AL) is a life-threatening complication, which increases morbidity, hospital stay and cost of treatment. The aim of this study is to identify risk factors, including intraoperative indocyanine green fluorescence angiography (ICG FA), associated with the leak of stapled colorectal anastomosis. METHODS: Four hundred twenty-nine consecutive patients underwent surgery between 2017 and 2019 for benign (n=10, 2.3%) or malignant (n=419, 97.7%) and rectal (n=349, 81.4%) or distal sigmoid (n=80, 18.6%) lesions with double-stapling technique reconstruction were included into retrospective study. Univariate analysis and multivariate logistic regression of the tumor-, patient- and treatment-related risk factors of AL was performed. RESULTS: An AL developed in 52 patients (12.1%). In multivariate analysis following variables were independently associated with AL; male sex (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.9-7.7; P<0.01), anastomosis at ≤6.5 cm from anal verge (OR, 3.1; 95% CI, 1.3-7.5; P=0.01), and age of ≤62.5 years (OR, 2.1; 95% CI, 1.1-4.1; P=0.03). ICG FA was found as independent factor reducing colorectal AL rate (OR, 0.4; 95% CI, 0.2-0.8; P=0.02). A nomogram with high discriminative ability (concordance index, 0.81) was created. CONCLUSION: ICG FA is a modifiable surgery-related risk factor associated with a decrease of colorectal AL rate. A suggested nomogram, which takes into consideration ICG FA, might be helpful to identify the individual risk of AL.

Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies in the world. It's estimated about 1.8 M new CRC cases worldwide per year. A somatic mutation in the BRAF gene in the tumor is a negative prognostic factor. This work is aimed at studying the clinical and genetic characteristics of Russian CRC patients with the BRAF mutation. The BRAF mutations were studied by Sanger sequencing and digital droplet PCR in 489 patients and found in 34 (7%) cases. The most common mutation was p.V600E (82%). Also, rare variants were found: p.K601E, p.N581I, p.G596R, and p.D594N. All the patients with rare mutations were characterized by an unfavorable prognosis of the disease. The clinical features of the patients with BRAF mutations in the study include the predominant primary tumor site in the rectum, in addition to the right colon. Then, most of the cases were diagnosed in the advanced stages of the disease and were represented by high-grade adenocarcinomas. This article demonstrates the feasibility of analysis of the entire exon 15 of BRAF gene in CRC patients regardless of tumor localization.

Unique Combination of Diamond-Blackfan Anemia and Lynch Syndrome in Adult Female: A Case Report.

We present an extremely rare clinical case of a 38-year-old Russian patient with multiple malignant neoplasms of the uterus and colon caused by genetically confirmed two hereditary diseases: Diamond-Blackfan anemia and Lynch syndrome. Molecular genetic research carried out by various methods (NGS, Sanger sequencing, aCGH, and MLPA) revealed a pathogenic nonsense variant in the MSH6 gene: NM_000179.2: c.742C>T, p.(Arg248Ter), as well as a new deletion of the chromosome 15's locus with the capture of 82,662,932-84,816,747 bp interval, including the complete sequence of the RPS17 gene. The lack of expediency of studying microsatellite instability in endometrial tumors using standard mononucleotide markers NR21, NR24, NR27, BAT25, BAT26 was demonstrated. The estimated prevalence of patients with combination of Diamond-Blackfan anemia and Lynch syndrome in the world is one per 480 million people.

Impact of oral antibiotic prophylaxis on surgical site infection after rectal surgery: results of randomized trial.

AIM: To evaluate the impact of oral antibiotic prophylaxis on surgical site infection (SSI) rate after rectal surgery. METHODS: It was a single-center 1:1 randomized controlled open parallel trial (registration number NCT03436719). The patients undergoing rectal resection for benign and malignant tumors were assigned randomly to two groups: the oral plus intravenous (IV) antibiotic prophylaxis (AP) and the IV antibiotic prophylaxis only. The primary endpoint was the overall rate of SSI. RESULTS: Between November 2017 and December 2018, 116 (male-55, the mean age-64 years) patients were enrolled into the trial. Of them, 57 had oral erythromycin 500 mg + metronidazole 500 mg a day before surgery and 1,000 mg of cephalosporin IV 30-90 min before operation. In the other group, 59 patients had the same IV antibiotics only. The incidence of SSIs was 22% (13/59) and 3.5% (2/57) correspondingly (р = 0.002). The statistically significant difference was detected for superficial SSI 0 (0%) vs. 5 (8.5%) (p = 0.03) and organ/space SSI 2 (3.5%) vs. 9 (15.3%) (p = 0.03), respectively. A multivariate analysis of risk factors of SSI identified two independent ones: bacterial contamination of the pelvic cavity ≥ 105 CFU at the end of surgery OR 17.9, 95% CI 2.1-150.0 (p = 0.008) and oral antimicrobial prophylaxis OR 0.2, 95% CI 0.03-0.8 (p = 0.02). CONCLUSION: Oral-parenteral AP significantly reduced the risk of SSI following elective rectal surgery. Bacterial contamination of the pelvic cavity ≥ 105 CFU at the end of surgery and oral antimicrobial prophylaxis were independent risk factors of SSI.

SeqURE - a new copy-capture based method for sequencing of unknown Retroposition events.

BACKGROUND: Retroelements (REs) occupy a significant part of all eukaryotic genomes including humans. The majority of retroelements in the human genome are inactive and unable to retrotranspose. Dozens of active copies are repressed in most normal tissues by various cellular mechanisms. These copies can become active in normal germline and brain tissues or in cancer, leading to new retroposition events. The consequences of such events and their role in normal cell functioning and carcinogenesis are not yet fully understood. If new insertions occur in a small portion of cells they can be found only with the use of specific methods based on RE enrichment and high-throughput sequencing. The downside of the high sensitivity of such methods is the presence of various artifacts imitating real insertions, which in many cases cannot be validated due to lack of the initial template DNA. For this reason, adequate assessment of rare (< 1%) subclonal cancer specific RE insertions is complicated. RESULTS: Here we describe a new copy-capture technique which we implemented in a method called SeqURE for Sequencing Unknown of Retroposition Events that allows for efficient and reliable identification of new genomic RE insertions. The method is based on the capture of copies of target molecules (copy-capture), selective amplification and sequencing of genomic regions adjacent to active RE insertions from both sides. Importantly, the template genomic DNA remains intact and can be used for validation experiments. In addition, we applied a novel system for testing method sensitivity and precisely showed the ability of the developed method to reliably detect insertions present in 1 out of 100 cells and a substantial portion of insertions present in 1 out of 1000 cells. Using advantages of the method we showed the absence of somatic Alu insertions in colorectal cancer samples bearing tumor-specific L1HS insertions. CONCLUSIONS: This study presents the first description and implementation of the copy-capture technique and provides the first methodological basis for the quantitative assessment of RE insertions present in a small portion of cells.

Risk factors and inflammatory predictors for Anastomotic Leakage following Total Mesorectal Excision with defunctioning stoma.

BACKGROUND: This study aims to examine the factors involved in anastomotic leak (AL) following low anterior resection and total mesorectal excision (LAR-TME) and to determine the usefulness of early measurement of the inflammatory biomarkers C-Reactive Protein (CRP) and Procalcitonin (PCT). METHODS: One hundred patients undergoing LAR-TME with a proximal diverting stoma were analyzed between 2013 and 2016. Postoperative CRP and PCT levels were measured on the 3rd and the 6th postoperative days. RESULTS: There were 11 clinical leaks with a negative impact in univariate analysis on AL of male gender, larger and stenotic tumours, intraoperative blood loss > 200 mL, the need for perioperative blood transfusion, postoperative anaemia and an operating time exceeding 180 minutes. On multivariate analysis, only perioperative blood transfusion was an independent AL risk factor. Recorded CRP was higher in AL patients when compared with non-AL cases on both the 3rd postoperative day (152.4 mg/L vs. 93 mg/L, respectively; P < 0.0001) and the 6th postoperative day (130.5 mg/L vs. 68.2 mg/L; P < 0.0001). The PCT levels also significantly differed between AL and non-AL cases on the 3rd postoperative day (0.5 ng/mL vs. 0.2 ng/mL, respectively; P < 0.0001) and the 6th postoperative day (1.16 ng/mL vs. 0.1 ng/mL, respectively; P < 0.0001). Both CRP and PCT showed high negative predictive values (NPV) for the diagnosis of an AL on both postoperative days. CONCLUSION: Following low restorative proctectomy, the high NPV of CRP and PCT measurements for the diagnosis of anastomotic leaks may assist decision-making for early hospital discharge.

Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease.

OBJECTIVE: To compare the clinical acceptability of micronized purified flavonoid fraction (MPFF) 1000 mg with MPFF 500 mg tablets, administered at the same daily dose in patients suffering non-complicated acute hemorrhoids. BACKGROUND: MPFF is an established treatment for hemorrhoidal disease. METHODS: This was a double-blind, multi-center, randomized study. Patients took either MPFF 1000 mg or 500 mg tablets for 7 days (daily dose; 3 g over 4 days followed by 2 g over 3 days). Adverse events were recorded in a patient diary. On day 7, anal pain and bleeding were assessed (visual analog scale [VAS] and Dimitroulopoulos scale, respectively). RESULTS: Patients (162) were randomized to MPFF 1000 mg (79) and MPFF 500 mg (83). No serious adverse events (AEs) occurred; 10 emergent AEs were considered treatment-related (6 for MPFF 1000 mg and 4 for 500 mg). Both regimens were associated with significant reduction in anal pain (VAS); -2.37 cm MPFF 1000 mg (P < 0.001) and -2.17 cm 500 mg (P < 0.001), with a slight trend in favor of MPFF 1000 mg (mean global reduction -2.27 cm, P < 0.001). Bleeding improved significantly in both groups of patients, 56% of patients on MPFF 1000 mg versus 61% on MPFF 500 mg. Bleeding ceased after treatment in 47% patients on MPFF 1000 mg versus 54% on 500 mg. CONCLUSION: After 7 days of treatment with MPFF at the same daily dose, both regimens reduced anal pain and bleeding. MPFF 1000 mg had a comparable safety profile to MPFF 500 mg, with the advantage of fewer tablets. Key limitations: Safety study.

Genome-scale analysis of DNA methylation in colorectal cancer using Infinium HumanMethylation450 BeadChips.

Illumina's Infinium HumanMethylation450 BeadChip arrays were used to examine genome-wide DNA methylation profiles in 22 sample pairs from colorectal cancer (CRC) and adjacent tissues and 19 colon tissue samples from cancer-free donors. We show that the methylation profiles of tumors and healthy tissue samples can be clearly distinguished from one another and that the main source of methylation variability is associated with disease status. We used different statistical approaches to evaluate the methylation data. In general, at the CpG-site level, we found that common CRC-specific methylation patterns consist of at least 15,667 CpG sites that were significantly different from either adjacent healthy tissue or tissue from cancer-free subjects. Of these sites, 10,342 were hypermethylated in CRC, and 5,325 were hypomethylated. Hypermethylated sites were common in the maximum number of sample pairs and were mostly located in CpG islands, where they were significantly enriched for differentially methylated regions known to be cancer-specific. In contrast, hypomethylated sites were mostly located in CpG shores and were generally sample-specific. Despite the considerable variability in methylation data, we selected a panel of 14 highly robust candidates showing methylation marks in genes SND1, ADHFE1, OPLAH, TLX2, C1orf70, ZFP64, NR5A2, and COL4A. This set was successfully cross-validated using methylation data from 209 CRC samples and 38 healthy tissue samples from The Cancer Genome Atlas consortium (AUC = 0.981 [95% CI: 0.9677-0.9939], sensitivity = 100% and specificity = 82%). In summary, this study reports a large number of loci with novel differential methylation statuses, some of which may serve as candidate markers for diagnostic purposes.