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considering location, form of growth, grade of the tumor, and lymph node dissection. Despite the fact that, in 28.2 % cases the volume of operation has been selected correctly, lymphadenectomy volume D2 has not been carried out, as required by the standard. As a consequences, in38.3 % cases the result was inadequate. A retrospective analysis represents that, early relapse was observed in all 128 cases, disease-free survival was 5.4 ± 0.4 months.
A retrospective analysis ofpatients in the control group (n=448) illustrates that, patients that have been carried out operations in compliance with all principles ofradicalism showed recurrences appeared only in 17 (3.8 %) cases within 5 years. Therefore, after subtotal resection the distal recurrence was detected in 7 (7.1 %) patients with gastric remnant, after proximal subtotal resection in 3 (9.7 %) and total gastrectomy in 7 (2.4 %) occasions. In 9 (52.9 %) cases, there was an early, and 8 (47.1 %) late recurrence.
As can be seen from the data presented the lowest rate of recurrence was observed after standard radical gastrectomy, which is 3 times less than distal subtotal resection and 4 times than proximal subtotal resection.
Consequently, we cannot exclude the adequacy of compliance with all the principles of radicalism in the performance of surgery in
this study. In spite of fact that most relapses occur on leaving a certain part of the stomach after distal and proximal subtotal resection, does not exclude the possibility of recurrence due to multicentric growth of SC, which is not always can be possible to determine. It has been proven thatthe duration of recurrence-free period was 22.4 ± 0.4 months in the control group, which isfour times more than in the main group.
Conclusion
It should be admitted that, the most important prognostic fac-toroftreatment of SC is a radicalism ofperformed surgery. Based on the above mentioned data it can be concluded convincingly that, the reasons for recurrence was non-compliance with the principles of radicalismin the main group, in comparison with the control group, wherewas a low rate of recurrence (3.8 %), duration of recurrence-free period 22.4 + 0.4months and in more than 47 % cases late relapse was diagnosed. This demonstrates the importance of minimization of negative prognostic factors affecting the abidance of the principles of radicalism. These comparisons has been proven absolutely, the main causes of recurrence of SC has been surgery, which was performed without taking into consideration factors that defines the significant role in the manifestation of early recurrent SC.
References:
1. Burdenko A. V. Combined and extended surgery of the gastric cancer: Diss. PhD in Medical Science. - M., 1999. - 271 p.
2. Zyryanov B. N., Kolomiets L. A., Tuzikov C. A. Stomach cancer: prevention, early detection, combined treatment, rehabilitation. -Tomsk, 1998. - 528 p.
3. Klimenkov A. A., Nered S. N., GubinG. I., et al. Forty years of experience in the surgical treatment of gastric cancer recurrence//Journal of Cancer Research Centernamed after Blohin N. N. - 1997. - № 4. - P. 28-33.
4. Black V. A., Schepotin I. B., Fedorenko Z. P. Treatment and prevention of recurrence of gastric cancer//Herald of Surgery. II Grekov. -1989. - № 8. - P. 60-61.
5. Chissov V. I., Vashakmadze L. A., Butenko A. V. Diagnostic and therapeutic -tactical faults in gastric cancer//Russian Journal of Oncology. - 1996. - № 2. - P. 18-21.
6. Giuli R. Recurrence following curative resection for gastric cancer//Journal for residents insurgery. - 2002.
7. De Manzoni G., Verlato G., Guglielmi A. et al.//Brit. J. Surg. - 1996. - V. 83, № 11. - P. 1604-1607.
8. Joypaul V., Browning M., Newman E. et al. Comparison of serum CA 72-4 and CA 19-9 levels in gastric cancer patients and correlations with recurrences//Am. J. Surg. - 1995. - V. 169, № 6. - P. 595-599
9. Reis E., Kama N. A., Doganay M. et al.//Hepatogastroenterology. - 2002. - V. 49. - P. 1167-1171.
Khudaykulova Gulnara Karimovna, Tashkent Medical Academy, Associate Professor, Department of Infectious and Pediatric Infectious Diseases E-mail: gulechkauz@rambler.ru
Dynamics of immunologic and virological indicators in HIV natural course in perinatally infected children
Abstract: The perinatal infection initiation route was revealed to be characterized by higher rates of immunodeficiency progression. It seems to be due to prenatal infection as well as early damage to the immature immune system of child by HIV. The virus concentration in perinatally infected children from the supervision start and by month 30 from the infection manifestation has been, accordingly, 5 and 2 times higher than in parenterally infected children that suggests a more adverse course of the disease when the child was infected vertically.
Keywords: HIV, children, perinatal transmission, CD4 Lymphocytes, viral load.
Background: The epidemic of HIV/AIDS is relatively recent in According to literature, in the absence of antiretroviral therapy
comparison with other countries with known history ofthe disease. (ART), the HIV-infection in perinatally infected children devel-The presented research of dynamics of immunologic and virologi- ops in one of the two variants: in 10-25 % of children, the infec-cal parameters in HIV-positive children depending on the route of tion quickly progresses with development ofAIDS and lethal com-transmission is the first for the time being [1; 3]. plications at the first year of their life, and in 75-90 % of children
Dynamics of immunologic and virological indicators in HIV natural course in perinatally infected children
the infection progresses much more slowly with the first AIDS symptoms occurring at the age of 8 years on average [2; 4; 5].
The basic laboratory parameters of HIV-infection progression are immunologic (CD4+ lymphocytes level) and virological (the HIV RNA concentration in blood — viral load).
Research objective
Revealing characteristic features of dynamics of immunologic and virological indicators in HIV natural course in children infected perinatally.
Study setting
The research has been conducted from 2008 to 2013 at the clinic of the National Centre to Struggle against AIDS and the HIV department of the Scientific Research Institute for Virology.
Criteria of inclusion:
• Verified diagnosis of HIV 1-infection;
• Age U5;
• No ART.
Material and methods
To study the dynamics of immunologic (CD4 + lymphocytes) and virological (viral load i. e. the HIV RNA concentration in blood) indicators the data of 40 children (Asians) at the age from 0 till 5 years with the diagnosis of HIV-infection have been analyzed. The diagnosis was made on the basis of clinical
35 30
and laboratory data according to MoH of Uzbekistan order 80 of 28.03.2012.
The children involved in the research were divided into groups depending on the route of infection initiation. Group 1 (the study one) included 20 children infected perinatally, 20 children with confirmed parenteral route of infection transmission composed group 2 (the control one). Only the children who were not on antiretroviral therapy (ART) have been included in the research. The children were not treated with ART for some reasons, e. g. the absence of clinical and immunologic indications, impossibility to ensure adherence to the treatment, refusal ofparents from the treatment, etc. The analysis ofthe dynamics of CD4+ lymphocytes and viral load in the children under study has been made in the following chronological sequence: 1 test on revealing HIV-infection, then in months 6, 12, 18, 24 and 30 after revealing ofthe infection or registration ofthe infant at a health center. As the enrolled children were under 5 years, the relative concentration of CD4 lymphocytes ( %) determined by the standard method (flow cytophotometry) has been analyzed. The viral load was evaluated by detection and determination of HIV RNA concentration in blood by the method of polymerase chain reaction (PCR — Real Time).
Results and discussion
The dynamic of CD4+ lymphocytes changes in children depending on the route of infection transmission are shown in Fig. 1.
25 20 15 10
30,3 ■ OS 0 77
____ 25,9 24,6 23,4
26 <->"> ri --
A A, J 21,5 1Q 3
16,2 14
6 month
12 month ■ Main group
18 month 24 month - Control group
30 month
Fig. 1. Dynamics of relative concentration of СD+ lymphocytes in children depending on the transmission route
As the figure demonstrates, the initial CD4 lymphocytes indicators in children on revealing the infection/health center registration varied depending on the transmission way. For instance, in children with a perinatal route, the initial CD4 lymphocytes values were lower and corresponded to the moderate or expressed degree of HIV-associated immunodeficiency (by the WHO classification), whereas in the control group, this indicator made 30.3 % on the average and, depending on child's age, corresponded to insignificant degree of immunodeficiency or its absence (according to the National Protocol "Rendering medical aid to HIV/AIDS children", appendix 5 to UzMoH order 88 of 30.03.2012).
It should be emphasized that at the time of the research, according to the National Protocol being in force in Uzbekistan, an-tiretroviral prevention in pregnant women began from 28 weeks of gestation (or from 24 weeks at the best). This can be a possible explanation of the fact that some children of the study group were infected by HIV prenatally and at birth they already had the developed failure in the system of immunologic response.
The further chronological analysis of CD4 lymphocytes showed that the speed of a decrease in the lymphocytes subpopulation in
blood was higher in the group of perinatally infected children. For instance, at month 30 after the start of the observation the indicator's average value made 14 %; it suggests severe immunodepression with no dependence on the child age. In month 30 in the group of parenterally infected children, the CD4 lymphocytes indicator made 23.4 % on the average (moderate immunodeficiency).
Lower speed of immunodeficiency progression in the group of parenterally infected children seems to indicate that in the given group, there was no actual infection transmission in the prenatal period and at early infant age when the immune system is immature and has not been fully formed. Thereupon, infection transmission in more advanced age was characterized by the better adaptation abilities of the child immunity contributing to supporting higher values of the CD4 lymphocytes level in the absence of antiretroviral therapy.
Thus, the analysis of the dynamics of CD4 lymphocytes indicator has shown that in children with perinatal HIV-transmission, severe immunodepression develops much faster that, in turn, predicts an adverse malignant course of the disease, unlike in children infected parenterally. It seems to be due the fact that children
with perinatal HIV transmission were infected before complete maturation of their immune system and both clinical manifestations and immunologic dysfunctions develop much faster than in elder children and adults.
The virological indicators (viral load, VL) do not recognize a HIV-infection stage (while immunologic and clinical data do) as the do not reflect a body condition (the immunity status), and indicate only the virus replication activity. While in adolescents and adults, the VL values can be used for predicting the risk of immunodeficiency development in future, while in children in
particular at the first year of their life it is difficult to do because of constant very high VL values.
Usually at birth, the viral load is < 10 000 copies/ml, later on, within first two months of life, it slowly grows to 100 000 copies/ml, and then slowly decreases by 4-5 years. Such dynamics of the viral load essentially differs from the dynamics of viral load in adults as fast enhancement and fast decrease in viral load are observed within several months after the HIV-infection acute stage [2].
The analysis of the dynamics of the viral load indicator (HIV RNA) in a natural course of the disease is presented in Fig. 2.
Fig. 2. Dynamics of the viral load in children
As it can be seen in the figure, in children with perinatal HIV transmission, much higher VL values were initially registered in comparison with the children of the control group; the values were almost 5 times higher than in the controls. As the disease progressed, the children of both groups showed an increase of HIV RNA concentration in blood. However, the VL values in both groups were not still equal. In month 30 from the start of the research, the VL indicators in the study group were 2 times higher than the values of the control group on the average.
There similar laws of viral load dynamics have been described and various explanations why children of early age infected vertically do not have an expressed decrease in the concentration of the virus in blood are offered [5]. According to one of them, at birth the child has incomparably higher levels of CD4 + lymphocytes, i. e. "there are more wood for the fire" and his/her immature immune system is not able to cope with a high concentration of the virus [1]. Another explanation concerning the HIV high concentration in vertical transmission of the infection suggests a transmission of virus strains which have mutated to escape the response of the mother's immune system. Since the child inherits half of mother's HLA alleles, the virus, having adapted to the maternal immune system, carries less antigen determinants which are able to form complexes with HLA molecules and to be recognized by the immune system [3; 4].
According to our findings the dynamics of viral load and that one of CD4+ lymphocytes have turned to be the independent and
depending on the infection transmission route
not interconnected criteria characterizing the course of perinatal-ly initiates HIV — infection (by Pirson's coefficient which in the study group was 0.137, in the control group — 0.262). Our findings are in agreement with the literature data. For instance, the metaanalysis of17 studies involving 3 941 children not on ART or receiving mono-therapy with zidovudin, has demonstrated that the viral load and quantity of CD4 lymphocytes are independent predicting markers of development of a terminal stage of the infection, AIDS and death [2]
Conclusion
Thus, in Uzbekistan, the characteristics of dynamics of the basic immunologic and virological parameters in HIV — infections in Asian children with a perinatal route of transmission in comparison with children infected parenterally have been studied. In perinatal transmission, the initially suppressed immune response of the child in the course of disease progression was determined to aggravate further and, after the lapse of 2-3 years from the time of infection transmission, severe immunodeficiency is being formed that predetermines an adverse clinical course of HIV-infection. Concerning the indicator of HIV viral load, an unfavorable trend was revealed as well which manifested itself in a high concentration of the virus that on the average is 2 times higher than in parenterally infected children. The revealed unfavorable trends dictate necessity and expediency of earlier ART start in children with perinatally transmitted HIV-infection to decrease the risk of development of the advanced stages of the disease and death.
References:
1. Douek D. C., Picker L.J., Koup R. A. T cell dynamics in HIV-1 infection//Annu. Rev. Immunol. - 2003. - 21: 265-304.
2. Dunn D. HIV Paediatric Prognostic Markers Collaborative Study Group. Short-term risk of disease progressionion in HIV- 1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis//Lancet. - 2003. - 362: 1605-1611.
3. Essajee S. M., Pollack H., Rochford G. et al. Early changes in quasispecies repertoire in HIV-infected infants: correlation with disease progressionion. AIDS Res.//Human Retroviruses. - 2000. - 16: 18: 1949-1957.
4. Goulder P.J., Brander C., Tang Y. et al. Evolution and transmission of stable CTL escape mutations in HIV infection//Nature. -2001. - 412:6844: 334-338.
5. Raquenaud M. et al. Excellent outcomes among HIV+ children on ART, but unacceptably high pre-ART mortality and losses to follow-up: a cohort study from Cambodia//BMC Pediatric. - 2009. - 9: 54.
