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Background: The aim of this prospective study was to determine the effect of mesenteric vascular evaluation using pre-operative multidetector computed tomography angiography (MDCTA) and intraoperative indocyanine green (ICG) angiography on reducing the anastomotic leak rate of colorectal cancer patients undergoing minimally invasive resection., Methods: Twenty-seven consecutive patients with colorectal cancer were studied, 18 males and 9 females, average age 69.1 ± 3.9 years. All patients underwent pre-operative mesenteric vascular evaluation using MDCTA with three-dimensional (3D) reconstruction and intraoperative evaluation of perfusion using ICG angiography. Twelve patients underwent laparoscopic resection (Olympus Visera Elite II OTV-S200) and 15 patients underwent robotic resection (DaVinci Si). Colorectal resection lines and anastomoses were guided by intraoperative ICG perfusion. Postoperative anastomotic leaks were assessed., Results: Pre-operative MDCTA 3D reconstructions defined the left colic and sigmoid artery anatomy and guided operative planning. The intraoperative ICG angiography resulted in a change of the planned lines of resection in seven patients (26%). The rate of postoperative anastomotic leaks in this study was 0% (0/27), compared to a leak rate of 6.8% at our institution in the preceding two years., Conclusion: Pre-operative evaluation of mesenteric vascular anatomy using MDCTA with 3D reconstruction and intraoperative evaluation of perfusion using ICG angiography were found to be technically feasible and safe. An appropriately designed study should be undertaken to prove whether it was truly effective at reducing the postoperative anastomotic leak rate in colorectal cancer patients undergoing minimally invasive resection at our institution., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Aim: In addition to ischemia there is also anastomotic ends tension proven to be a risk factor for anastomotic leak. HT vascular ligation is accepted as a rule, in attempt to achieve tension-free anastomosis. LT is a preferred option, based on the more accurate preservation of proximal intestinal segment microperfusion and lower risk of damage to the hypogastric plexus. The aim of this study is evaluation of comparative indicators in high tie (HT) and low tie (LT) laparoscopic rectal resections., Methods: A prospective nonrandomized comparative cohort study of patients in our department with cancer of the rectum in clinical stage I-III, operated on in laparoscopic approach over a 6-years period., Results: For the period 2015-2020, a number of 208 laparoscopic surgeries have been done for rectal cancer. Patients were divided into three groups-group A with HT vascular ligation 116 pts. (69%), group B-53 pts. (25%), underwent low ligation-LT and group C-39pts. (19%) low tie plus lymph node dissection of the apical LN group (LT-appic LND). The distribution was made without randomization, based on the operators' expertise. Anastomotic leaks were 3.8% in group A, 3.0% in group B and 2.9% in group C (p > 0.05) with no significance difference. There is no significant difference in the number of lymph nodes obtained in group A and group B, while in group C the number of the harvested lymph nodes was higher (p < 0.05). The indicators for intestinal / defecation dysfunction, as well as for urinary/sexual dysfunction, according to our data, are significantly more favorable in patients with LT, in contrast to the other two groups., Conclusion: HT vascular ligation attempts to achieve tension-free anastomosis and more harvested lymph nodes. However, LT could be a preferred option, based on the lack of significant evidence for a difference in specific oncological survival and due to more accurate preservation of proximal intestinal segment microperfusion to prevent anastomosis dehiscence, also for its lower risk of damage to the hypogastric plexus. Splenic flexure mobilization provides elongation of the proximal intestinal segment, but has no proven effect on anastomotic leakage incidence. It increases surgical duration and is in fact necessary in up to 30% of the cases. At the present moment there is no precise data whether LT has an advantage in terms of prevention of autonomic nervous and urogenital dysfunction. New prospective randomized and highly probative studies are needed to standardize the procedures in specific clinical situations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) Background: We aimed to analyze currently available studies with intraoperative radiotherapy (IORT) as a choice of treatment where the Xoft Axxent ® electronic brachytherapy (eBx) system was used as a single-dose irradiation and an exclusive radiotherapy approach at the time of surgery in patients with early breast cancer (EBC). We also compared the results of the systematic review to the Bulgarian experience. (2) Methods and Materials: We performed a systematic review of the studies published before February 2021, which investigate the application of a single-fraction 20 Gy radiation treatment, delivered at the time of lumpectomy in EBC patients with the Xoft Axxent ® eBx System. A systematic search in PubMed, Scopus, and ScienceDirect was performed. The results are reported following the PRISMA guidelines. The criteria on patients' selection for IORT (the additional need for EBRT), cosmetic outcomes, and recurrence rate from the eligible studies are compared to the treatment results in Bulgarian patients. (3) Results: We searched through 1032 results to find 17 eligible studies. There are no published outcomes from randomized trials. When reported, the cosmetic outcomes in most of the studies are defined as excellent. The observed recurrence rate is low (1-5.8%). Still, the number of patients additionally referred to postoperative external breast radiotherapy (EBRT) is up to 31%. Amongst the 20 patients treated in Bulgaria, the cosmetic outcomes are also evaluated as excellent, five of which (25%) are referred for EBRT. Within median follow-up of 39 months, there was one local and one distal recurrence. (4) Conclusions: Current evidence demonstrates the Xoft Axxent ® eBx system as a safe and feasible technique for IORT delivery in EBC patients. There are no randomized controlled trials conducted at this time point to prove its long-term effectiveness. Better patient selection and a reimbursement strategy have to be proposed to extend the application of this technique in Bulgaria.

Background: Anastomotic leakage (AL) is one of the most severe complications in colorectal surgery. Currently, no predictive biomarkers of AL are available. The aim of this study was to investigate the role of C reactive protein (CRP) to albumin ratio (CAR) as a predictor of AL in patients undergoing elective surgery for colorectal cancer., Materials and Methods: Data on 1183 consecutive patients surgically treated for histologically proven colorectal cancer in the surgical units involved in the study were collected. Data included sex, age, BMI, ASA score, Charlson comorbidity index, localization, histology and stage of the disease, as well as blood tests including albumin and CRP at the 4th postoperative day. Differences in CAR between patients who developed AL and those who did not were analyzed, and the ability of CAR to predict AL was investigated with ROC analysis., Results: CAR was significantly higher in patients with AL in comparison to those without, at the 4th postoperative day. In ROC analysis CAR showed a good ability in detecting AL (AUC 0.825, 95%CI: 0,786-0,859), greater than those of CRP and albumin alone. CAR also showed a high ability in detecting postoperative deaths (AUC 0.750, 95% CI 0,956-0,987). These findings were confirmed in multivariate analysis including the most relevant risk factors for AL., Conclusion: Our study evidenced that CAR, an inexpensive and widely available laboratory biomarker, adequately predicts AL and death in patients who underwent elective surgery for colorectal cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate a series of blood count inflammation indexes in predicting anastomotic leakage (AL) in elective colorectal surgery., Methods: Demographic, pathologic, and clinical data of 1432 consecutive patients submitted to colorectal surgery in eight surgical centers were retrospectively evaluated. The neutrophil to lymphocyte (NLR), derived neutrophil to lymphocyte (dNLR), lymphocyte to monocyte (LMR), and platelet to lymphocyte (PLR) ratios were calculated before surgery and on the 1st and 4th postoperative days, in patients with or without AL., Results: There were 106 patients with AL (65 males, mean age 67.4 years). The NLR, dNLR, and PLR were significantly higher in patients with AL in comparison to those without, on both the 1st and 4th postoperative days, but significance was greater on the 4th postoperative day. An NLR cutoff value of 7.1 on this day showed the best area under the curve (AUC 0.744; 95% CI 0.719-0.768) in predicting AL., Conclusions: Among the blood cell indexes of inflammation evaluated, NLR on the 4th postoperative day showed the best ability to predict AL. NLR is a low cost, easy to perform, and widely available index, which might be potentially used in clinical practice as a predictor of AL in patients undergoing elective colorectal surgery.

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 ( MBD2 ) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

Background: Rectal carcinoma is one of the most common cancers on a global scale. Although there were major improvements in its treatment during the last two decades, surgery is still the only curative method. However, is often complicated and can cause disorder of different aspects of the patients self-perception of health. The aim of this study is performing ofa meta-analysis for evaluation and comparison of the quality of liferesults after rectal cancer treatment., Methods: Search of relevant articles, which were published between 2000 and 2015, was performed. The outcomes of abdominoperineal resection and anterior resection were analyzed with the EORTC's quality of life measuring instruments - quality-of-life questionnaire C30 (QLQ-C30)and quality-of-life questionnaire CR38 (QLQ-CR38). The assessment score, appropriate for the survey, was established at least one year after radical surgery. The Statistical Package for Social Sciences (SPSS) package of IBM Statistics, version 19 was used for the statistical analyses., Results: 13 studies, published between 2001 and 2015, have been presented in this meta-analysis. Data from 1805 patients,with a mean age of 64.7 years, have been included. When comparing Miles extirpation and sphincter-sparing operations,statistical significance was detected for the following variables:social functioning (74.6 ± 8.5 vs. 83.4 ± 8.6, P = 0.045),constipation (11 ± 8.4 vs. 22.6 ± 8.3, P = 0.032), and body image (67.9 ± 14 vs. 82.5 ± 9.1, P= 0.01)., Conclusion: Preservation of the sphincter is a better treatment option that should be carefully considered. Dependently registered differences, our conviction for the rectal cancer care concern needs individualization of the approach in this surgery.It is essential that the policy of avoidance of abdominoperineal resection (APR) cannot currently be justified on the grounds of quality-of-life (QoL) results alone., (Celsius.)

Introduction: Retroperitoneal tumors, in general, are rare tumors which histopathological characteristics and biological behavior can be considered as benign or malignant. They originate from various tissue elements located in the retroperitoneal space. They often cover Anatomical structures of varying importance - mainly retroperitoneal vessels and organs, which determines the type of surgery - radical or palliative. They are composed of adipose tissue, vascular elements, smooth and striated muscle, neural elements germline structures. There are three main types of retroperitoneal tumors: mesodermal, neurogenic and teratosarcomas. As mentioned above each can be either benign and malignant. In most cases there are no specific symptoms except general weakness, heaviness in the abdomen, loss of appetite, progressive weight loss, headache and fever. The pain is most often located in the lumbosacral area. The tumor can also cause disturbances in urination. In patients with advanced stage can be observed significantly symmetrical or asymmetrical tumor growth in the abdominal area. The most commonly used techniques for the diagnosis of the disease are X-ray, CT-scan and MRI., Material and Methods: Retrospective study involving 112 cases operated in the clinic for 14-years period (2000-2014) - 101 patients, 11 of them were operated on twice in a different time interval on the occasion of relapsed malignant process., Results: Out of all operated cases, 42% are males (47 cases) and 58% - women (65 cases). In most cases (72% - 81 cases) tumors are malignant. All patients were treated surgically. There were followed up a total of 89 patients over a period of 3 months to 8 years (96 months) as of the studied malignant cases 3 year survival was observed in 21 patients, and one patient has survived 96 months after total extirpation of fibrosarcoma. Early postoperative mortality (till 20th postoperative day) was registered in 3 patients - 2.67% of all operated cases., Discussion: About 80% of primary retroperitoneal extra-organ tumors are generally malignant. People of all ages are affected equally and no statistically significant difference in the number of men and women is detected. There are many theories about the emergence of retroperitoneal tumors, but currently none of them has not been fully proven. Treatment depends on the type of the lesion. Surgery is the main approach and it should be applied to both benign and malignant lesions. In the case of malignancy other methods than surgical are chemo- and radiotherapy but they are less effective.

There is an established standard for the surgical treatment of rectal neoplasms. Every conventional operation can be performed by means of laparoscopy, if the complex approach to the disease and classical oncological principles are observed. Depending on the height of tumor, surgical operations, different in tactical and technical terms, are performed. The correct preoperative staging, planning, and securing of resources guarantee the favorable outcome of therapy. The main advantages are the less postoperative pain and briefer hospital stay. The better visualization of pelvic organs and routine use of high-energy sources reduce the blood loss and potential complications. With a view to ensure modern treatment of this major group of patients, the input of the required resources, for turning into one of the routine methods of rectal cancer treatment, is a necessity. ABBREVIATIONS USED: LAR (laparoscopic anterior resection), LLAR (low laparoscopic anterior resection), LIsRR (laparoscopic intersphincteric resection of the rectum), TME (total mesorectal excision), TATME (transanal total mesorectal excision), LER (laparoscopic extirpation of the rectum), IMA (inferior mesenteric artery), and IMV (inferior mesenteric vein).

Objectives: FoxP3 expression is a marker for Tregs which are known to be involved in tumor immunity. We aimed to evaluate FoxP3 promoter demethylation in human colorectal cancer (CRC) and rat intrahepatic cholangiocarcinoma (ICC)., Design and Methods: Bisulfite-treated genomic DNA templates of shock frozen paired samples were studied from 13 anonymous CRC patients and from 10 male rats (n=6 ICC induced by thioacetamide and n=4 age-matched controls). Real-time PCR was carried out using a LightCycler 480 system. Human FoxP3 and CD3 promoter demethylations were estimated using previously described assays; and rat FoxP3 promoter demethylation using a newly developed assay., Results: A significant 3.5-fold increase of the demethylation in FoxP3 promoter region was found in human CRC and rat ICC (P<0.05). The average frequency of cells with FoxP3 demethylation in patients suffering from CRC was 0.26% in normal tissue and 0.92% in tumor tissue (n=11 paired samples). Although, no significant difference was found between the mean frequency of CD3 demethylation in normal tissue (4.80%, n=6) and in tumor tissue (4.14%, n=6) from CRC patients, the ratio of demethylated CD3/FoxP3 promoter areas was significantly lower in tumor specimens (P<0.05). Using our novel assay, we found a significant increase in mean frequencies of cells with FoxP3 demethylation in rats with ICC (7.42%, n=6) in comparison to controls (2.14%, n=4)., Conclusion: FoxP3 seems to be an interesting biomarker for immune response to epithelial tumors. Functional consequences from the increase of Tregs remain to be demonstrated. Further studies with outcome data are necessary., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The Peutz-Jeghers syndrome is inherited condition, characterized by hamartomatous gastrointestinal polyposis and with mucocutaneous pigmentation. We have experienced a case with typical clinical features, diagnosed before complication's development. In order to prevent cancer setting it is recommended to perform aggressive screening and high-technological procedures.

Neoplasms of the rectum represent a common therapeutic problem, with plenty of different possible operative decisions for low-situated tumor cases. Some unfavorable consequences of these surgical approaches seriously affect the patient's life. From the surgical point of view, sparing the sphincter can be considered as achievement of the desired result. This seldom matches what the operated people expect before and experience after the treatment. The necessity of critical assessment of the used operative techniques arises with the rectal cancer surgery development. Despite their undeniable attractiveness, sphincter- sparing operations (SSO) are not accompanied with the awaited result in every case. A need of feedback mechanism arises to control vacillation from saving sphincter by all means to the tremendous number of abdominoperineal excisions (APE). With the introduction of the integral psychometric term "Quality of Life" (QoL) a possibility for a dynamic control over the obtained results was created. This control is realized by a set of instruments. These tools help measure objectively the results taken, as well as their practical use aiming to optimize our treatment policy. Recognition of their modifications and principles could be a step forward for the best interpretation.

The integral psychometric term quality of life illustrates the subjective sensation of the received results. The instruments developed by EORTC contribute to its dynamic objectification and optimization, by applying the adequate practice. For patients with rectal carcinoma this marker is expected to have a prediction value, like other markers that determine the progress of the disease.

Introduction: The recent development of rectal surgery is related to the possibility of avoiding permanent stoma formation, which is presumably believed to be the main factor that decreases quality of life. Despite the modern views of the disease, the adequacy of complex treatment and the technical improvements, low anastomoses often result in poor bowel function. The subjective perception of health is changed for these patients. There arises the question of adequacy of operative approach. The aim of our investigation was analysis of the present QoL data of patients treated in the Specialized Oncology Hospital of Veliko Tarnovo., Materials and Methods: The quality of life of 173 patients was examined with the help of EORTC questionnaires QLQ C30 and QLQ C38. The comparison is between a group with high anterior resection (N1 = 50-28.9%), a group with low sphincter-sparing operation (N2 = 59-34.3%) and primary extirpated patients (N3 = 53-30.8%). They were questioned preoperatively, in an early and late aspect, as well as before prophylactic stoma closure., Results: The high resected patients present the best QoL values. Performing the extirpation leads to significant preoperative drop and a good adaptation afterwards. Their indexes are not much different from anterior resection group. Compared with the low technique group considerable improvement as regards the scales social functioning and global health status (P < 0.05) was observed. This group has high values of general and specific symptomology (pain, constipation, diarrhea, dyspnoea, financial difficulties, defecational problems and sexual dysfunction) generating low QoL. Their recovery is prolongated in relation with the drop of the modules before the prophylactic stoma closure., Conclusion: The best health perception available after treating the rectum carcinoma is for high located tumors. We recon that for patients with extirpation techniques and primary stoma formation there is no objective data of QoL decrease. In comparison, the group with low rectal resections had to undergo another operative intervention, and there were some specific complications and following poor function reducing quality of life. The requirement for very precise selection of patients must be fulfilled.

The increased number of sphincter-spared patients after low rectal resection requires an up-to-date approach, aiming at better functional results. The authors modify into practice the transverse coloplasy pouch, with a longitudinal seromuscular incision, mucosal liberalization and transverse suture. They describe their experience with this feasible technique in different types of low rectum resections. The conception of the technique is with increased neorectal volume to avoid some unpleasant consequences of this surgery, without changing the oncological effectiveness. The modification with a single-layer suture facilitates the technique, has some advantages and does not worsen the desired effect.

With the rectal cancer surgery development arise the necessity of critical assessment of the operative techniques used. Although its undeniable attractiveness, the sphincter-sparing operations are not in every case accompanied with the desired effect. With the introduction of the integral psychometric term "quality of life" a possibility for a dynamic control over the obtained results was created. This control is realized by a set of instruments. These instruments help to objective the results measurement, as well as their practical use aiming to optimize our treatment policy.

Purpose: Variation in genetic factors together with xenobiotic exposure may result in increased risk of colorectal cancer. The P-glycoprotein (P-gp) is highly expressed in the apical membrane of enterocytes, where it pumps xenobiotics from the enterocytes back into the intestinal lumen. Thus, polymorphisms that reduce the activity of the MDR1 (ABCB1) efflux pump are potential risk factors for colorectal carcinogenesis. The aim of the present study is to genotype the MDR1 2677G>T (rs2032582) and 3435C>T (rs1045642) polymorphism in patients with colorectal cancer and controls and to identify a possible association between individual genetic variation and susceptibility to colorectal cancer., Methods: In the present study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy Bulgarian volunteers were evaluated for the two polymorphisms in MDR1. Polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analyses on a LightCyclertrade mark (Roche Diagnostics, Mannheim, Germany)., Results: No differences were found between the frequencies of the two mutant alleles in the tumor tissue from the cases and lymphocytes from the controls [frequencies of 2677T: 43.5% in patients and 44.1% in controls; frequencies of 3435T: 48.3% in patients and 50.9% in controls (both P > 0.05)]. The MDR1 polymorphic sequence of the tumor tissue always matched that of normal intestinal tissue from the same patient. Consequently, genotyping of DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA., Conclusions: The present study suggests that MDR1 2677G>T and 3435C>T polymorphism is not a risk factor for sporadic colon cancer among Bulgarians and that somatic mutation at these sites is not involved in the genesis of colon tumors. Further examination using larger number of samples must be necessary to reach to more reliable conclusions.

Background: The purpose of the study was to genotype four polymorphisms in CYP3A5 (CYP3A5*2, CYP3A5*3, CYP3A5*3B, and CYP3A5*6) for a possible association between individual genetic variations and susceptibility to colorectal cancer. Another point of interest was to conduct a comprehensive analysis in tumor and normal intestine tissue from the same patient, searching for somatic hotspots., Material and Methods: In our study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy volunteers were enrolled. CYP3A5 polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analysis on a LightCycler., Results: The allele frequencies were comparable in both groups: frequency of CYP3A5*2 = 0.3% in patients vs. 0.6% in controls; frequency of CYP3A5*3 = 90.8% in patients vs. 93.1% in controls; in both groups no CYP3A5*3B and CYP3A5*6 variants were detected (p > 0.05). No difference was observed between genotype frequencies in tumor and surrounding normal tissues of 80 patients., Conclusions: The CYP3A5 variants are unlikely to have an important functional significance in patients with colorectal cancer. The studied CYP3A5 loci do not seem to be hotspots for somatic mutation. DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA for genotyping of these polymorphisms.