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Siberian journal of oncology

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Vol 17, No 3 (2018)
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https://doi.org/10.21294/1814-4861-2018-17-3

EPIDEMIOGICAL STUDIES

5-10 1730
Abstract

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

11-19 1809
Abstract

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.

20-27 1316
Abstract

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.

28-33 1084
Abstract

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.

34-40 1557
Abstract

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

41-50 1212
Abstract

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

51-57 1536
Abstract

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.

58-63 1105
Abstract

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.

64-71 39990
Abstract

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.

72-76 889
Abstract

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

77-87 1252
Abstract

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.

88-93 1381
Abstract

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.

94-100 1107
Abstract

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.

101-108 990
Abstract

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

109-114 1212
Abstract

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.

115-121 2131
Abstract

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.



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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)