Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

Colorectal anastomosis in rectal cancer surgery: methods of anastomotic leakage prevention

One of the most serious complications after low anterior resection is the failure of sutures of colorectal anastomosis, which is the most common surgical complication that results in patient’s death. Promptly diagnosed anastomotic leakage in postoperative period is challenging. Nevertheless, elimination of risk factors in preoperative period can significantly reduce complication rates.The purpose of this review article is to analyze possible risk factors and methods for preventing colorectal anastomosis leakage.An important area of prevention and optimization of treatment options for anastomotic leakage is the development of prognostic measures to eliminate risk factors. We see the prospects for this direction in the introduction of a nomogram, which allows the surgeon to assess the possible outcomes of the operation, to choose the optimal tactics with a minimum risk of complications, as well as the introduction of methods to avoid or prevent the development of complications of colorectal anastomosis.

Cervical cancer in the Russian Federation and the risks of vaginal fistula

This review aims to provide up-to-date information on the factors associated with an increased risk of vaginal fistula in women with cervical cancer, as well as on methods of their prevention and treatment. It includes data on various types of vaginal fistulas in cervical cancer patients and risk factors for their development, according to foreign and Russian research articles published over the last 20 years. Cervical cancer is one of the most challenging oncological diseases in the Russian Federation, because it is detected at stage III–IV in more than 30 % of women. Such a high incidence of cervical cancer and the need for radiotherapy determine high risk of fistulas, which significantly impairs the quality of life. Thus, identification of factors associated with vaginal fistulas, as well as methods of their prevention and treatment remains a highly relevant task for the Russian healthcare system.

Three-year outcomes of sandwich therapy in patients with locally advanced cancer of the middle and lower rectum

Background. The most important criteria for the effectiveness of the treatment of locally advanced rectal cancer are indicators of overall survival (OS) and disease-free survival (DSF). Conducting systemic chemotherapy in addition to chemoradiotherapy at the preoperative stage can increase these indicators.Objective: to study analyze the indicators of 3-year OS and DFS, as well as the frequency of local relapses and distant metastases.Materials and methods. From 2013 to 2020, 72 patients with T≥3(CRM+)N0–2M0 lower and middle ampullar rectal cancer were included in the study using sandwich therapy. At the first stage, 2 courses of induction polychemotherapy were carried out according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). Further, chemoradiation therapy was carried out with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation. After the end of chemotherapy, the patients underwent 2 courses of consolidating polychemotherapy according to the CapOx scheme (capecitabine 2000 mg/m2 orally for 14 days and oxaliplatin 130 mg/m2 intravenously once every 3 weeks). The control group consisted of 72 patients who underwent neoadjuvant treatment in accordance with current clinical guidelines (chemotherapy course with a total focal dose of 50–56 Gy while taking capecitabine 1650 mg/m2 per day orally on the days of irradiation).Results. In 19 (26.4 %) patients from the study group and in 6 (8.3 %) patients from the control group, the achievement of pCR was recorded (p = 0.006). The overall complication rate was 48 (66.7 %) in the study group and 37 (51.4 %) in the control group (p = 0.072), the frequency of grade III–IV toxicity was 8 (11.1 %) and 7 (9.7 %), respectively (p = 0.072). Sphincter-sparing surgical interventions were performed in 52 (72.2 %) and 40 (55.6 %) patients in the sandwich-therapy group and the control group of chemoradiation therapy, respectively (p = 0.037). Resection in the R0 volume was achieved in 71 (98.6 %) and 72 (100 %) patients, respectively (p = 0.316).Conclusion. The use of sandwich therapy is a promising trend in the treatment of patients with locally advanced rectal cancer. There were no significant differences in the frequency of 3-year OS (96.1 % versus 91.5 %, p = 0.247), DFS (89.8 % versus 84.0 %, p = 0.117) and local relapses (0 % versus 4.2 %, p = 0.997). In our study, statistically significant differences were obtained in the incidence of distant metastases (6.9 % versus 18.1 %, p = 0.05), which may indicate a positive trend towards an increase in OS and DFS rates.

Biochemical markers of ovarian stromal cell tumors

Ovarian stromal cell tumors are a rare group of neoplasms that characterized by an ambiguous prognosis and biological activity associated with the hypersecretion of a number of substances. The review presents the latest data on the biochemical diagnosis of tumors of the stroma of sex cord, including granulosa cell tumor of the ovary. The importance of hormones,

Genetic and epigenetic profiling of the BRCA1 / 2 genes in solitary ovarian cancer and multiple primary ovarian tumors

Background. Ovarian cancer is a complex and poorly studied disease that kills nearly 70–80 % of patients. Therefore, practitioners are interested in any opportunity of improving survival of these patients. From this point of view, investigation of genetic and epigenetic functions associated with this pathology is quite promising.Objective: to assess clinical and morphological characteristics of tumors in ovarian cancer patients, considering the presence of mutations and methylation in the BRCA1/2 gene.Materials and methods. This study included 180 ovarian cancer patients (FIGO stage I–IV) treated in the N. N. Blokhin Russian Cancer Research Center between 2008 and 2019. Study participants were divided into 3 groups according to their BRCA status and the number of primary tumors. We collected and analyzed venous blood, biopsy samples of ovarian cancer, archived histological sections, and paraffin-embedded tissue blocks. DNA isolated from venous blood was used to identify the following germline mutation by pyrosequencing: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, and BRCA26174delT. DNA isolated from biopsy specimens and paraffin-embedded tissue specimens was used to analyze methylation in the promoter regions of the BRCA1 and BRCA2 genes by bisulfite sequencing (PyroMark Q24 DNA Sequencer; Qiagen, USA) with specific primers targeting promoter regions of the BRCA1 and BRCA2 genes.Results. Molecular testing demonstrated that the frequency of BRCA1 gene mutations was 21.1 % (38/148) in patients with solitary ovarian cancer and 40.6 % (13/32) in patients with multiple primary ovarian cancers. The frequency of methylation of the BRCA1 gene promoter was 2.2 % (18/148) in patients with solitary ovarian cancer and 3.1 % (1 case) in patients with multiple primary ovarian cancers. All BRCA1 methylated ovarian tumors were serous adenocarcinomas, including high grade tumors in 15 patients (78.9 %) and low-grade tumors in 4 patients (21.1 %).Conclusion. Hypermethylation of the BRCA1 gene promoter was observed only in individuals with sporadic serous ovarian cancer. No methylation was detected in patients with non-serous ovarian cancer, as well as in patients carrying BRCA1 gene mutations (both with solitary ovarian cancer and with primary multiple ovarian tumors).

Toxicity and efficacy of biosimilar bevacizumab in the second-line therapy for metastatic colon cancer in routine clinical practice: results of an independent observational study

Objective: to compare the efficacy and tolerability of second‑line chemotherapy with original bevacizumab (Avastin) and biosimilar bevacizumab produced by “Biocad” (Avegra) in patients with metastatic colon cancer.Materials and methods. This retrospective observational study included patients with metastatic colon cancer treated in 9 clinics in the Russian Federation. Inclusion criteria were as follows: metastatic or locally advanced colon cancer and second‑line therapy with bevacizumab (Avastin or Avegra). The primary outcome measure was overall survival (OS). Secondary outcome measures included progression‑free survival (PFS), disease control rate (DCR), and incidence of adverse events associated with antiangiogenic therapy.Results. We identified 209 patients with metastatic colon cancer who received second‑line therapy with biosimilar bevacizumab (n = 37; 17.7 %) or original bevacizumab (n = 90; 43 %) or no targeted therapy (n = 82; 39.3 %) between 2014 and 2018. Patients in these three groups were matched for their main prognostic characteristics. The DCR was 59.5 % in the group of biosimilar bevacizumab, 58.9 % in the group of original bevacizumab, and 50 % in the control group (without targeted therapy). PFS was 6 months in the chemotherapy group and 8 months in the groups of bevacizumab (hazard ratio (HR) 0.77; 95 % confidence interval (CI) 0.65–0.91; p = 0.002); the difference in PFS between patients receiving biosimilar bevacizumab and original bevacizumab was insignificant (HR 1.3; 95 % CI 0.81–2.1; р = 0.3). Median OS was 16 months in the chemotherapy group, 30 months in the biosimilar bevacizumab group, and 20 months in the original bevacizumab group (HR 0.89; 95 % CI 0.72–1.1; р = 0.3). We observed a tendency to longer OS in patients receiving biosimilar bevacizumab (HR 0.44; 95 % CI 0.17–1.1; р = 0.08). Bevacizumab‑ associated toxicity was limited to arterial hypertension and was registered in 4 patients with only one patient who developed grade III hypertension.Conclusions. There was no significant difference in PFS between patients receiving biosimilar and original drug, while OS was higher in the group of biosimilar bevacizumab. Both medicines demonstrated similar toxicity. Therapy with biosimilar bevacizumab ensured lower incidence of hypertension and proteinuria compared to the original drug. An additional prospective observational study assessing the efficacy and tolerability of biosimilar bevacizumab in colon cancer patients is needed.

Evolution of treatment for rectal fistula: from resection to FiLaC® laser ablation

Rectal fistula – one of the most common coloproctological diseases. Annually, thousands of patients with anal fistula have had treated around the world. Treatment of this disease is an actual problem in coloproctology nowadays due to the high frequency of recurrence and anal incontinency. The chronic persistent perianal suppuration and multiple surgical interventions the main predictor of emergence of the anal incontinence, which could be achieve almost 50 %, according the literature data. The risk of emergence the anal incontinence is particularly high in the treatment of complex fistulas. Therefore, the problem of complex rectal fistulas treating remains an actual task in the clinical practice of a coloproctologist.

Assessing the risk of postoperative mortality in patients undergoing emergency surgery for complicated colorectal cancer

Objective: to analyze factors affecting the mortality of patients who have undergone emergency surgeries for complicated colorectal cancer.Materials and methods. In this retrospective study, we evaluated treatment outcomes of 112 patients who underwent surgeries for complicated colorectal cancer in 3 clinical hospitals of Smolensk between 2014 and 2019. We included patients with moderate or severe disease (ASA II or III) who have undergone emergency resections for intestinal obstruction or tumor perforation. We assessed clinical, laboratory, and tumor‑associated factors affecting postoperative mortality.Results. Patients’ gender had no significant impact on postoperative mortality (p = 0.69). Mean age of study participants was 65 years (range: 43–86 years). Age also did not affect postoperative mortality; most of the patients both among those died (n = 19) and survived (n = 93) were older than 60 years (p = 0.46). We observed no significant correlation between tumor location and postoperative mortality (p = 0.27). Of 19 patients with lethal outcomes, five died due to pulmonary embolism. They have elevated level of D‑dimer, which was significantly higher than that in survivors (p = 0.014). The lowest mortality was observed in patients who have undergone two‑stage surgeries with tumor removed at the second stage compared to patients operated on using other techniques (p = 0.041). Using multivariate logistic regression, we identified independent factors that affected mortality. They included: tumor perforation (odds ratio (OR) 2.8; 95 % confidence interval (CI) 1.2–7.6; p = 0.003), severe comorbidity (OR 1.6; 95 % CI 1.7–8.2; p = 0.02), D‑dimer level >510.1 ± 10.2 ng/L (OR 1.5; 95 % CI 1.3–4.5; p = 0.01), type of surgery, namely resections with primary anastomosis formation and two‑stage surgeries with tumor removal at the first stage (OR 1.2; 95 % CI 1.1–6.3; p = 0.04).Conclusions. Tumor perforation, cardiovascular disease in combination with other comorbidities, type of surgery (resections with primary anastomosis formation and two‑stage surgeries with tumor removal at the first stage), and elevated preoperative level of D‑dimer had the most significant impact on postoperative mortality.

Features of treatment rare forms of stromal cell ovarian tumors

Objective: identification and description of clinical and morphological characteristics of rare forms of stromal cell tumors of the ovaries.Materials and methods. Retrospectively processed over 10 thousand case histories of patients with various ovarian tumors who were examined and treated at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia and the National Center for Oncology and Hematology of the Ministry of Health of Kyrgyz Republic. In 473 patients were diagnosed stromal cell tumors, among them 3 cases of rare forms of tumors of the stroma of the sex cord were identified: stromal tumor from Sertoli cells, malignant luteoma of the ovary, lipid‑cell tumor from Leydig cells. All patients underwent a planned morphological study of surgical material and immune-histochemical study.Results. The detailed data of clinical observations of rare types of tumors, which was presented in the literature by isolated cases, are presented, the description of which in the literature is presented by isolated cases. The possible effect of clinical and morphological characteristics on the survival of patients with rare forms of stromal cell tumors of the ovaries were analyzed.Conclusions. The necrobiotic changes in the tumor, the degree of malignancy, and the stage of the disease are potential predictors of poor prognosis in patients with rare forms stromal cell tumors of the ovaries which require confirmation in a larger sample of patients.