Soluble B7-H3 in Colorectal Cancer.

We present the results of comparative ELISA of the concentration of soluble form of immunity checkpoint B7-H3 (sB7-H3) in the serum of patients with colorectal cancer (CRC) at different stages before treatment and healthy control donors. The analysis revealed a statistically significant difference between the median levels of sB7-H3 in the blood serum of CRC patients (19.66 ng/ml) and healthy donors (16.76 ng/ml) (p=0.0025). ROC analysis showed 62.9% sensitivity and 56.7% specificity for CRC patients (cut-off 17.62 ng/ml; p=0.0028). An association of sB7-H3 levels with tumor progression was revealed. We demonstrated that sB7-H3 levels were significantly lower in patients with regional metastases than in patients without metastases (p=0.039) and that sB7-H3 concentration tends to decrease at the late stages of the disease. Thus, high serum level of sB7-H3 in CRC patients can be a favorable prognostic factor in future.

[Combined treatment of rectal cancer with moderate risk of tumor progression]. / Rezul'taty primeneniya kombinirovannogo metoda lecheniya bol'nykh rakom pryamoi kishki so srednim riskom progressirovaniya opukholevogo protsessa.

OBJECTIVE: To increase the effectiveness of combined treatment in patients with rectal cancer and moderate risk of progression based on the concept of polyradiomodification (PRM). MATERIAL AND METHODS: The study included 337 patients with rectal cancer and moderate risk of tumor progression. A short course of radiotherapy (cRT) (5x5 Gy) combined with several radiomodifiers (cRT+PRM) was performed in 147 (43.6%) patients. Other 190 (56.4%) patients underwent cRT. The following radio modifiers were used: three-time application of local microwave hyperthermia (Yacht-3 or Yacht-4 devices), two-time intrarectal delivery of a biopolymer composition with Metronidazole before the 3rd and 5th irradiation sessions and two-week oral administration of Capecitabine (Xeloda) at a daily dose of 2.0 g/m2. Surgery was performed in 4-6 weeks after radiotherapy. RESULTS: CRT+PRM program increased 5-year relapse-free survival up to 81.3% compared to 60.3% after cRT alone (p=0.0003) due to significant reduction of the incidence of cancer recurrence from 8.4% to 0.7% (p=0.0013). More effective local growth control expanded the indications for sphincter-sparing surgery. These procedures were performed in 89.1% and 70.5% of patients, respectively (p=0.00001). In the cRT+PRM group, sphincter-sparing surgery reduced incidence of cancer recurrence from 13.7% to 0.8% (p=0.0110), distant metastases - from 23.9% to 13.7% (p=0.00349). CONCLUSION: Radiomodification in neoadjuvant radiotherapy is justified in patients with moderate risk of tumor progression, improves long-term results and increases the incidence of sphincter-sparing surgery.

Blood Serum Zonulin in Colorectal Cancer, Autoimmune Bowel Diseases, and Irritable Bowel Syndrome.

Zonulin content in blood serum of patients with colorectal cancer (CRC; n=152; 30-84 years) and patients with large bowel adenomas (n=32; 39-82 years) was measured by standardized kit IDK Zonulin ELISA (Immundiagnostik AG). The healthy control group (n=50) comprised volunteers (27 women, 23 men; 25-68 years); pathological control group (n=84) - patients (55 women, 29 men;18-84 years) with irritable bowel syndrome (n=29), Crohn's disease (n=5), and ulcero-necrotic colitis (n=50). In comparison to healthy control group, the level of zonulin was significantly increased in CRC patients (p<0.0000001) and in patients with benign large bowel tumors (p<0.004), as well as in patients with inflammatory intestine diseases and with irritable bowel syndrome (p<0.0002). Zonulin level in blood serum of CRC patients was slightly, but significantly higher (p<0.05) than in the group of pathological control. ROC curve construction revealed that at optimal zonulin cut-off level (52.2 ng/ml), the diagnostic sensitivity of CRC detection was 66.7% and specificity relative to healthy control was 81.8%. The specificity relative to the combined control group (healthy control+non-tumor bowel diseases) was only 68.9%. Thus, no acceptable cut-off levels for differentiation between malignant and benign tumors, as well as between tumor and non-tumor large bowel pathologies were found. Analysis of the associations between serum zonulin level and the main clinical and pathological characteristics of CRC demonstrated that the level of this marker increased with disease progression (p<0.01; Kruskal-Wallis test), but was not associated with individual criteria of the TNM system, tumor localization, histological structure, and malignancy grade.

Prognostic significance of the TNM system criteria, levels of serum insulin-like growth factors and their transport proteins, VEGF and MMP-7 in colorectal cancer.

The analysis of long-term results of treatment of 88 primary patients with colon adenocarcinoma at various stages of tumor process is presented, taking into account the TNM system criteria, and serum IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, VEGF, and MMP-7 levels. The overall survival rate assessed by Kaplan-Meier method and Cox multivariate regression model was used as the criterion of prognosis. It was established that IGF-1, IGFBP-2 and VEGF serum levels along with the stage of colorectal cancer might be considered as statistically significant independent predictors of overall survival in patients.

Immunosuppression Factors PD-1, PD-L1, and IDO1 and Colorectal Cancer.

Due to the low efficiency of immunotherapy for colorectal cancer (CRC), it is extremely promising and relevant to study the mechanisms of immunosuppression. In this work, a comprehensive study of the expression of soluble and tissue forms of PD-1 and PD-L1 in blood serum and tumors of patients with CRC, as well as IDO1 in tumors was performed for the first time. The diagnostic and prognostic significance of the studied parameters was determined. A statistically significant decrease in the number of soluble forms of PD-1 and PD-L1 in the blood serum and the association of the number of PD-L1+ cells in the stroma of tumors with the CRC stage were established. The absence of correlations between soluble and tissue forms of the studied proteins was shown, indicating the presence of independent mechanisms of immunosuppression in CRC, which may explain the ineffectiveness of immunotherapy for this type of tumor.

[Transanal mesorectumectomy for rectal cancer - is it optimal surgery for 'difficult' patients?] / Transanal'naia mezorektuméktomiia pri rake priamoi kishki - optimal'noe khirurgicheskoe vmeshatel'stvo dlia 'slozhnykh' patsientov?

AIM: To compare short-term outcomes after transanal total mesorectumectomy (Ta-TME) and laparoscopic (Lap-TME) procedure in 'difficult' patients. MATERIAL AND METHODS: Prospective nonrandomized trial included patients with confirmed middle-/low rectum adenocarcinoma T1-4aN0-2M0 for the period November 2013 - September 2016. We identified 20 out of 55 in TA-TME and 14 out of 54 patients in Lap-TME group as those of 'difficult' subgroup: male, BMI ≥25 кг/м2, previous chemoradiotherapy (CRT). RESULTS: Time of surgery, blood loss, conversions rate, postoperative morbidity and length of hospital-stay were similar in both groups. Hardware anastomoses were more frequent in TA-TME compared with LAP-TME group (78.9% vs. 50%, p=0.086). Specimen quality was more favorable in TA-TME group: Grade I 10% in Ta-TME group vs. 28.6% in Lap-TME group; 'positive' CRM 5% vs. 14.3%, р=0.365. Within-group analysis did not reveal any differences between 'difficult' and 'typical' patients by surgical and pathomorphological characteristics in TA-TME group in contrast to Lap-TME group. Median of follow-up was 24.6 (IR 10.6-40.2) and 23.8 (IR 12.1-39.9) months for TA-TME and Lap-TME groups, respectively. Local recurrence occurred in 1 (1.8%) 'difficult' patient after Ta-TME. Distant metastases were observed in 1 (1.8%) patient of Ta-TME and 2 (3.7%) patients of Lap-TME group. Actuarial 3-years reccurence-free survival was 95.7% for Ta-TME and 93.9% for Lap-TME group, respectively (p=0.923). CONCLUSION: TA-TME is advisable for 'difficult' patients. Further multicenter randomized trials are necessary to specify the effectiveness of TA-TME in these patients.

[Total mesorectal excision in rectal cancer management: laparoscopic or transanal?].

AIM: To evaluate and compare intraoperative features, early surgical outcomes, quality of excised specimen after laparoscopic and transanal total mesorectal excision (LA-TME and TA-TME). MATERIAL AND METHODS: Prospective randomized study included 45 patients with confirmed rectal adenocarcinoma (cT2-4N0-2M0) since October 2013. LA-TME and TA-TME groups consisted of 23 and 22 patients respectively. Inclusion criteria were patients with primary-operable rectal cancer and satisfactory response after neoadjuvant chemo- and radiotherapy. Both groups were comparable in stages of cancer, age and body mass index (BMI). Median length from anal edge was 6.5 cm and 7 cm in TA-TME and LA-TME groups respectively. There was significantly greater number of patients after chemo- and radiotherapy in TA-TME group (86% vs. 48%, p=0.006). RESULTS: Surgery time was 305 and 320 minutes in LA-TME and TA-TME groups recpectively, median blood loss -- less than 100 ml. Mean hospital-stay was 8.0 days in both groups. Each group had 1 conversion including laparoscopic procedure in TA-TME group. Transanal extraction of specimen was performed in 86% vs. 48% in TA-TME and LA-TME groups respectively (p=0.021). Complications (Clavien-Dindo sclale) were observed in 27% and 26% in TA-TME and LA-TME groups respectively without statistically significance. Complications IIIb, IVb and V degrees were not diagnosed in TA-TME group. Also in this group «good¼, «satisfactory¼ and «unsatisfactory¼ quality of TME was obtained in 68%, 14% and 18% of cases. At the same time in LA-TME group these values were 74%, 9% and 17% respectively (p=0.859). One of operated patients had «positive¼ lateral edge (TA-TME). Median distal edge of resection was 21 mm and 23 mm in TA-TME and LA-TME groups respectively. CONCLUSION: Preliminary data show comparable early outcomes after transanal and laparoscopic techniques. Laparotomy and associated compications are avoided in case of transanal extraction of specimen. Further researches are necessary to study functional and long-term results.

Short-term outcomes after transanal and laparoscopic total mesorectal excision for rectal cancer.

BACKGROUND: Transanal total mesorectal excision (taTME) has potential benefits of better visual control, especially in male patients with a high body mass index and low rectal cancer. However, this method has not yet been validated in clinical trials. The aim of this study was to compare the short-term outcomes of transanal and laparoscopic (lap) TME. METHODS: From October 2013 to January 2015, consecutive patients undergoing transanal or laparoscopic TME for biopsy-proven mrT1-4aN0-2M0 rectal cancer were included in a prospective database. Patients with Eastern Cooperative Oncology Group performance status 2 and higher and patients undergoing partial mesorectal excision were excluded. This analysis focused on short-term surgical outcomes. RESULTS: From October 2013 to January 2015, 22 taTME procedures and 23 laparoscopic TME procedures were performed. Patient characteristics were comparable between groups, but more patients in the taTME group underwent neoadjuvant (chemo) radiotherapy (87 vs. 48 %, p = 0.006). Median operative time was 320 min in the taTME group and 305 min in the lapTME group. There was one conversion in each group, but the transanal procedure was converted to laparoscopic resection. Transanal specimen extraction was performed in 86 versus 48 % patients in taTME and lapTME groups accordingly (p = 0.021). There was no post-operative mortality and post-operative morbidity in the taTME and lapTME groups was similar (27 vs. 26 %). One patient in the taTME group had positive circumferential resection margins. Oncologic results from resected specimens were comparable. CONCLUSIONS: Our initial experience demonstrates comparable short-term results for taTME and lap TME. Further investigation is necessary to assess long-term functional and oncologic outcomes.

[Neoadjuvant chemotherapy for colorectal cancer--time to learn a new treatment strategy?].

The article discusses the possibility of neoadjuvant chemotherapy in colon cancer patients and rectal cancer patients without the additional use of radiation therapy. The possible risks and benefits of such approach are analyzed and the data of available clinical studies are provided.

[Polyradiomodification as component of combined treatment of rectal cancer: rationale and results].

The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow-up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented.

[Combined treatment for rectal cancer using different radiomodification means].

The paper presents an evaluation of the results of surgical and combined treatment received by 961 patients at the Center's Clinics within 28 years. The analysis was based on 3 protocols of prospective randomized study. It dealt with assessment of the end results of surgical and combined treatment for operable rectal cancer using one preoperative hyperfractonated STD of 5-25 Gy. That was combined with local microwave hyperthermia and two radio modifiers--local microwave hyperthermia+intrarectal administration of a preparation containing metronidazolum. Due to the latter factor, the rate of 3-year relapse-free survival rose considerably. Also, loco-regional and distant metastasis incidence was cut down due to superior ablasticity of surgery.

[Surgical tactics in the esophago-gastric hemorrhages of liver cirrhosis patients]. / Khirurgicheskaia taktika pri pishchevodno-zheludochnykh krovotecheniiakh u bol'nykh tsirrozom pecheni.

The character of the source and rate of bleeding were taken into consideration in determining the surgical tactics in 342 patients with cirrhosis of the liver complicated by gastro-esophageal bleedings and with high risk of their appearance. The operation of choice is thought to be arrest of the gastro-esophageal collateral blood flow. At high portal pressure or its considerable growing after the separating operation the latter should be associated with vascular anastomosis. When cirrhosis of the liver is associated with ulcer disease of the duodenum the separating operation should be added by selective proximal vagotomy, for ulcer disease of the stomach--by a parsimonious resection.