EPIDEMIOGICAL STUDIES
A retrospective epidemiological analysis of the mortality from respiratory system cancer among the population of the Tomsk region for a ten-year period was carried out using data drawn from the official population and mortality statistics of the Tomsk region. Cancer has the second leading cause of death behind cardiovascular disease. Respiratory system cancer is the 3-rd most common cause of cancer-related death after cancers of the digestive system and genital organs. The standardized mortality rate for respiratory system cancer among the rural population is significantly higher than that in the urban population (p<0.05). Over the study period, the respiratory system mortality rate decreased for males (р=0.0000) and remained relatively constant for females. The lifetime risk of dying from respiratory system cancer in 2016 in the Tomsk region was higher than the national average. For men, it was the highest among the main localizations. Compared to 2007, the mortality rate decreased, as the risk of lung cancer death in men decreased. The lifetime risk of dying from respiratory system cancer was higher in the rural population than in the urban population. The indicator of «severity» of the disease indicates an unfavorable situation in terms of quality and completeness of statistical recording of patients and early diagnosis of respiratory cancer, especially in urban areas of the Tomsk region. In order to ensure timely and adequate routing of patients with suspected malignant neoplasm and timely diagnosis, the continued implementation of the Population-based Cancer Registry with coverage of all administrative territories and areas is of great importance.
CLINICAL STUDIES
More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable tumors receive adjuvant endocrine therapy. Patients with metastatic ER+ breast cancer also receive hormone therapy as first-line treatment. Patients with ER+/PR+ locally advanced breast cancer including potentially operable cases (cT2N1, cT3N0M0) are still a subject to neoadjuvant chemotherapy in most of the oncology centers in Russia and worldwide. More than 10 years ago, several trials evaluating the efficacy of neoadjuvant endocrine therapy were conducted in the Petrov Research Institute of Oncology (aromatase inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs neoadjuvant chemotherapy, etc.) The primary endpoint was the evaluation of pathologic complete/partial response to therapy and the frequency of breast-conserving surgeries following neoadjuvant treatment. We now represent 10-year long-term follow-up data on comparison of neoadjuvant chemotherapy with neoadjuvant endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study results show tendency to better 10-year disease-free survival in patients with luminal-A breast cancer who received endocrine therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9 %, respectively, p=0.062) There were no statistically significant differences in DFS rates among patients with the luminal B breast cancer subtype (41 % vs 40 %) The discovery of biomarkers of potential resistance to endocrine therapy (cycline-dependant kinase activity [cdk 4/6], estrogenreceptor mutation [ESR1], mTOR signaling pathway activity, co-expression of the ER and HER2neu [ER+/ HER2neu3+]) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the armamentarium of endocrine-therapy for not only metastatic and locally-advanced but also operable cases of ER+ breast cancer.
Purpose. We analyzed the frequency and severity of hematologic, hepatic and pancreatic toxicity during and after completion of neoadjuvant chemoradiotherapy in patients with gastric cancer.
Material and methods. Phase II clinical trial was conducted to evaluate the efficacy of the combined modality treatment including neoadjuvant chemoradiotherapy followed by D2 gastrectomy for patients with locally advanced gastric cancer. The main inclusion criteria were: histologically verified gastric cancer, cT3-4N0, cT2-4N1-3; M0. Before starting neoadjuvant therapy, all patients underwent thoracic and abdominal CT and laparoscopy to exclude peritoneal carcinomatosis. A total dose of radiation therapy was 45 Gy (1 + 1.5 Gy/fraction/day with a 4–5 hour interval) concurrently with the modified CAPOX chemotherapy regimen. Gastrectomy or subtotal resection of the stomach was planned 4-6 weeks after the completion of chemoradiotherapy. The toxicity assessment of neoadjuvant chemoradiotherapy was performed using the NCI CTC scale, version 3.0. The assessment of hematological, hepatic and pancreatic toxicities was done.
Results. Among the toxicity during and after completion of neoadjuvant chemoradiotherapy, thrombocytopenia, neutropenia and leukopenia (grade 1–2) were the most common, requiring no additional symptomatic therapy. Radiation therapy was completed in 45 (98 %) patients. Chemotherapy was completed in 42 (91 %) patients. The median time between the completion of chemoradiotherapy and surgery was 44 days. Surgery following chemoradiotherapy was performed in 100 % of patients, including R0 resection in 93 % of patients.
Conclusion. Preoperative chemoradiotherapy was well tolerated by patients, could be completed in most cases and did not prevent subsequent surgical treatment.
The aim of the study was an attempt to improve the results of organ-preserving treatment of patients with localized renal cell carcinoma by developing and using abdominal intermuscular mini- flank approach to the kidney.
Material and methods. We analyzed the data of 119 patients who underwent partial nephrectomy for renal cell carcinoma at the N.N. Petrov National Medical Research Center of Oncology from 2004 to 2013 years from three types of surgical approach: through an open classical lumbotomy, laparoscopically and through the original abdominal intermuscular mini-flank approach. The following parameters were studied: the duration of the operation, the time of renal artery ischemia, the volume of blood loss, the number of patients requiring hemotransfusion, as well as the oncological and functional results of partial nephrectomy, the cosmetic effect and the frequency of the formation of chronic postoperative pain.
Results. It is demonstrated that the proposed original intermuscular mini- flank approach as well as laparoscopic approach provides a good cosmetic effect, preserves the function of the anterior abdominal wall and reliably reduces the incidence of chronic postoperative pain compared to open classical lumbotomy.
The purpose of the study was to improve treatment outcomes for patients with inoperable colorectal liver metastases using the combination of chemoembilization of the hepatic artery and radiofrequency ablation.
Material and methods. Treatment outcomes of 60 patients with methachronic unresectable liver metastases from colorectal cancer were analyzed. Eligibility criteria were as follows: absence of extrahepatic metastases, size of metastases from 3 to 5 cm, and inability to perform resection. All patients were divided into two groups. Group I included 30 patients who received combination of regional chemotherapy and radiofrequency ablation. Group II (the control group) consisted of 30 patients who received radiofrequency ablation only.
Results. Post-embolization and post-ablation syndromes were observed in both groups of patients. Rightsided hydrothorax (Clavien-Dindo grade II) was found in 4 out of 60 patients (2 patients in Group I and 2 patients in Group II). One-, two- and three-year disease-free survival rates in Group I patients were 96.6 %, 76.6 % and 53.3 %, respectively. The corresponding rates in the control group patients were 90.0 %, 53.6 % and 30.0 %, respectively (p=0.049). The overall one-, two-and three-year survival rates in Group I patients were 100 %, 90 % and 63.3 %, respectively. The corresponding rates in the control group patients were 100 %, 70 % and 50.0 %, respectively (p=0.202).
Conclusion. The combination of regional chemotherapy and radiofrequency ablation led to the improvement in overall and disease-free survival rates.
LABORATORY AND EXPERIMENTAL STUDIES
Background. A functionally significant TP53Arg72Pro polymorphism can contribute to the development of gastric cancer (GC).
The aim: to study the associations of genotypes and alleles of the TP53Arg72Pro 4 polymorphism with GC and biomarkers of gastric ucosal atrophy in population-based prospective and case-control clinical trials among the population of Siberia.
Material and methods. As a part of the epidemiological study, data of the international multicenter HAPIEE project for 2003–05, based on a population sample of residents of Novosibirsk city (serum and DNA samples) and data of the population-based registry of GC (2012) were compared. Gastric cancer patients were matched by age and sex to HAPIEE population controls. A total of 156 serum samples (GC – 52, control – 104) and 146 DNA samples (GC – 50, control – 96) were available for prospective analysis. DNA samples from 80 gastric cancer patients (45 men and 35 women, mean age 61.0 ± 13.4 years) and from 87 age-and sex-matched controls were analyzed. DNA samples from venous blood were genotyped according to standard methods. Serum samples were tested using diagnostic kit for enzyme-linked immunosorbent assays to determine the levels of pepsinogen I (PGI), PGII, PGI/PGII ratio, gastrin-17 and IgG antibodies to H. pylori.
Results. No differences in genotype and allele frequencies of the TP53 gene between the case group and the control group were found. A decreased frequency of the Pro allele in female gastric cancer patients compared with controls indicated that the Pro allele is protective against the development of gastric cancer, but this effect was not observed in male patients. No associations of TP53 genotypes with the risk of diffuse or intestinal gastric cancer, as well as with the age and sex of patients were found. A high frequency of genotypes with the Pro allele in patients with stage III–IV gastric cancer indicated the relationship between Arg/Pro TR53 and tumor progression, in particular, the contribution of the minor Pro allele to the unfavorable prognosis. A prospective study showed high risk of reducing the level of pepsinogen for assessing predisposition to gastric cancer.
Conclusion. Two case-control studies (population and clinical) conducted in the Western Siberia found no relationship between the TP53Arg72Pro polymorphism and the risk of gastric cancer. However, the TP53 genotype with a rare Pro allele was associated with atrophic gastritis and severity of gastric cancer.
ONCOLOGY PRACTICE
Reconstruction of head and neck defects after surgery for cancer remains challenging. The choice of the reconstruction technique depends on the tumor size and localization, type of the defect, patient’s age, concomitant diseases, and disease prognosis. Surgeons have currently a broad range of material for reconstructive surgery, from free flaps to revascularized flaps. Microsurgical reconstruction has made a revolution in treatment of patients with complex head and neck defects. However, the use of this technique may not be advisable for some patients. The search for new techniques is needed to improve functional and aesthetic results and reduce traumatism without compromising oncologic outcomes. Thirty-six patients underwent surgery with reconstruction using the submental island flap, a new alternative in the reconstruction of various head and neck defects. The graft was taken after making a neck incision for neck lymph node dissection. A few patients develop total and marginal necrosis of the graft. Short- and long-term results showed no worsening of oncologic outcomes in the selected group of patients.
We present our experience in using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer patients treated at Irkutsk Regional Cancer Center. All patients were divided into 2 groups. Group I consisted of 15 patients, who underwent cytoreductive surgery only. Group II comprised 17 patients, who underwent surgery and HIPEC. The main eligibility criteria for this study were verified peritoneal carcinomatosis and resectable ovarian cancer. The primary analysis of these groups included: preoperative period, length of operation, postoperative length of stay, and postoperative complications. The technique of performing HIPEC using Performer HT® (RAND, Medolla (MO), Italy) was completely described. Further study is required to estimate the difference in overall and disease-free survival between study groups.
Background. Radiation-induced damage to the pelvic organs (post-radiation proctitis, cystitis, urethritis) is a frequent complication after radiotherapy for prostate cancer. The reported frequency of late radiation damage to the pelvic organs is up to 30 %.
Material and methods. The paper presents treatment outcomes of 149 with radiation-induced pelvic injuries caused by brachitherapy (15 patients) and combination treatment including brachitherapy and external beam radiation therapy (28 patients) for stage T1–3N0M0 prostate cancer. Radiationinduced rectitis (proctitis) was revealed in 149 patients and complications of the urinary tract after radiation treatment were noted in 107 (72 %) patients. Potency failure was observed in 98 % of cases. All patients received conservative treatment and 8 (5 %) of these patients underwent surgery after inefficient conservative treatment.
Results. Favorable effect of conservative therapy of radiation-induced rectitis was obtained in 141 (95 %) patients. Eight (5 %) patients underwent colostomy due to the formation of vesicle-rectal fistula. Chemical cauterization of the mucosa of the bladder and rectum in patients with erosive hemorrhagic and hemorrhagic rectitis and cystitis was effective and safe. The frequency of post-radiation complications was found to be less after brachitherapy than after combination treatment using brachitherapy and external beam radiation.
Actuality. In the conditions of modern development of medicine constantly there is an improvement of existing and emergence of new methods of treatment of oncological diseases. The use of high- tech methods of medical care for the treatment of cancer allows to increase the survival rates in the detection and subsequent treatment of malignant neoplasms. This circumstance causes the appearance of patients with cancer desire not only to cure this underlying disease, but also to preserve the quality of life that preceded it. Often, patients of reproductive age wish to realize their reproductive function. The article analyzes the possibilities of the medical organization, when detecting breast cancer in a patient of childbearing age, to use methods of treatment aimed at the implementation of the patient’s reproductive rights.
Purpose of research. To perform the law on the protection of public health, which provides patient before the start of anticancer therapy kryokonservierung oocyte.
Results. It is noted that such opportunities are limited by the current legislation that does not grant the right to persons with such cancer at the expense of the budget to use the methods of assisted reproduction and cryopreservation technologies to maintain their reproductive potential. The article substantiates the need to consolidate the possibility for women of childbearing age who have breast cancer and want to realize their reproductive function after treatment before chemo - and radiation therapy to receive and cryopreservate with the subsequent storage of oocytes, embryos or ovarian tissue at the expense of the budget.
REVIEWS
Recently many new approaches for repurposing or repositioning of the clinically used drugs have been developed. Drug repurposing allows not only to use known schemes for the synthesis of biologically active compounds, but also to avoid multiple studies that are necessary for drug approval process – analysis of pharmacokinetics, carcinogenicity, acute and chronic toxicity, including cardiotoxicity, nephrotoxicity, allergenicity etc. It makes possible to reduce the number of experimental studies as well as costs of investigations. In cancer research drug repurposing includes screening for medicines used nowadays for the treatment of patients with non-cancer diseases which possess anticancer activity or able to enhance the effects of the standard anticancer chemotherapy, and search for new applications of known anticancer drugs for the treatment of different cancer types. Scientific rationale for the search of the compounds with potential anticancer properties among drugs with different applications is based on the multiple cross-talks of signaling pathways, which can inhibit cell proliferation. Modern advances in genomics, proteomics and bioinformatics, development of permanently improving databases of drug molecular effects and high throughput analytical systems allow researchers to analyze simultaneously a large bulk of existing drugs and specific molecular targets. This review describes the main approaches and resources currently used for the drug repurposing, as well as a number of examples.
The purpose of the study was to present data on polymixin-based antibiotics with activity against infections caused by multidrug- resistant Gram-negative bacteria, such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
Material and methods. The review includes data from clinical as well as in vitro studies for the period 1998–2017. The search for relevant sources was carried out in the Medline, Cochrane Library, Elibrary and other databases.
Results. The analysis of the data showed the presence of synergism and additive activity of polymyxin in combination with carbapenems, rifampicin and azithromycin. However, experimental data showed no direct positive correlation between combination of polymyxim and azithromycin/ rifampicin. In clinical studies, in hospital-acquired pneumonia, including ventilator-associated pneumonia, the clinical response rate of polymyxin B combined with other antibiotics ranged from 38 % to 88 %. High nephro-and neurotoxicity of polymyxin observed in previous studies can be explained by a lack of understanding of its toxicodynamics or the use of an incorrect dose.
Conclusion. Polymyxin B in combination with other antibiotics is a promising treatment against infectious complications caused by multidrug resistant Gram-negative bacteria.
The aim of the study was the pharmacokinetic and pharmacogenetic analysis of analgetic efficacy and safety of transdermal fentanyl for cancer patients.
Material and methods. A comprehensive search for journal articles
published between 2012 and 2017 was carried out using PubMed, Scopus, Web of Science, and E-library databases.
Results. The analysis of the data showed that pharmacokinetic and pharmacogenetic factors can influence the interindividual variability of analgesic therapy with fentanyl TTC for cancer patients, predetermining phenotypic differences in the efficacy and safety of analgesia. Enforced polypharmacotherapy with the use of inducers or inhibitors of the CYP3A4 isoenzyme activity can significantly change the effectiveness of analgesic therapy and result in undesirable side effects of strong opioids. Contradictory data on the effect of some single nucleotide polymorphisms of metabolic genes, transport genes and mu-opioid receptor genes dictate the necessity of further studies in this field.
Conclusion. To date, there is no single explanation for interindividual variability of analgesic therapy with fentanyl TTS. A comprehensive assessment of the pharmacokinetic and pharmacogenetic factors affecting the efficacy and safety of analgesic therapy with potent opioids is a tool of a personalized approach for anesthesia in clinical oncology.
The purpose of the study was a systematic literature review of imaging assessment of lymph node metastasis in patients with laryngeal and hypopharyngeal cancer.
Material and methods. In order to review the most relevant scientific literature available, we searched Elibrary, Medline databases (from January 2005 to December 2017). Of 735 identified studies, 32 were assessed.
Results. The role of ultrasonography, spiral computer tomography, magnetic resonance tomography, positron emission tomography in the assessment of regional metastatic spread in patients with laryngeal and hypopharyngeal cancer was analyzed. All these imaging techniques failed to reliably identify clinically occult lymph node metastases. However, the choice of treatment options for laryngeal and hypopharyngeal cancer depends considerably on the diagnostic accuracy. In this context, the concept of sentinel lymph nodes deserves special attention.
Conclusion. Further studies of the sentinel lymph node concept using various radiopharmaceutical drugs in the detection of preclinical regional metastasis in patients with laryngeal and hypopharyngeal cancer are required.
CASE REPORTS
Metastases to the heart are extremely rare, and the reported incidence of cardiac metastasis at autopsy ranges from 1.5 to 21.8 %. In cancer patients, cardiac metastases are usually difficult to diagnose unless the patients do not complain of any related symptoms. Common tumors with cardiac metastasis potential are usually carcinomas of the lung, breast, and malignant lymphoma. The prognosis of a metastatic heart tumor is unfavorable. The average life expectancy for patients with this diagnosis is less than six months. In addition, surgical treatment of primary cardiac tumors or metastatic cardiac tumors is associated with high risk of perioperative lethality. Case report. We present a rare case of cervical cancer metastasis to the heart in a 33-year-old woman. Cytological examination revealed no evidence of disease recurrence 14 months after the completion of external beam radiotherapy. Echocardiography showed a mass in the outflow tract of the right ventricle and findings of severe pulmonary hypertension. omputed tomography and magnetic resonance imaging revealed a large right ventricular thrombus. The patient underwent surgery with artificial circulation. Pathohistological and immunohistochemical studies revealed metastasis of squamous cell carcinoma. The control echocardiography showed decrease in pulmonary hypertension. No evidence of right ventricular mass was detected. Conclusion. Cardiac metastasis should be included in the differential diagnosis in patients with complaints of dyspnea and chest pain, especially in cases with history of cancer. Surgical treatment of cardiac metastasis contributes to the prevention of cardiopulmonary complications and improvement of survival rates in this group of patients.
Background. Serous cystic pancreatic neoplasm is a rare pancreatic tumor, accounting for 1–2 % of all pancreatic tumors. In 2010, mixed serous neuroendocrine cystic neoplasia was included into the classification of the WHO for pancreatic tumors. Only a few cases of this disease have been reported in the literature. Mixed serous neuroendocrine cystic neoplasia is often associated with von Hippel Lindau disease. Most authors recommend surgery as a main treatment of this disease.
Case report. We present a case with mixed serous neuroendocrine cystic neoplasia not associated with von Hippel Lindau disease. The patient underwent spleen – preserving distal pancreas resection. The diagnosis was histologically and immunohistochemically verified. There is no evidence of disease recurrence within 10 months after surgery. Conclusion. Histological examination of the resected serous cystadenoms should take into account the possibility of combining this pathology with pancreatic neuroendocrine tumors. For the purpose of verification, the use of immunohistochemical examination is required. Radical surgical resection allows patients with this disease to be cured.
ISSN 2312-3168 (Online)