CC BY
14
both University hospitals in our town Ruse, with leading specialist on this field from Sofia. Sharing of experiences among participants was accepted as beneficial.
CONCLUSIONS:
Theoretical knowledge and practical management of TIVAD is already a less serious problem for Bulgarian medical community. In our country from 2 years placement of ports is a routine technique especially before chemotherapy. But creating guidelines for nursing care of patients with implanted ports is still recommended, as some departments do not have such rules. They are crucial for improving the patients quality and length of life. A real fact is that nurses and midwifes working with critically and chronically ill patients do not have enough authority to draw up individual plans for comprehensive care for TIVAD (ports). This problem is a challenge for the teaching team in our department. We should consider and include a special emphasis in training programs for Special nursing and midwifes care.
References: Список литературы:
[1]. Amr Mahmoud Abdel Samad, Yosra Abdel-zaher Ibrahim, Complication of Port A Cath implantation: A single institution experience, The Egyptian Journal of Radiology and Nuclear Medicine, Vol. 46, Issue 4, December 2015, p. 907-911
[2]. Couban S, Goodyear M, Burnell M, et al: Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. J Clin Oncol 23:4063-4069, 2005.
[3]. De Cicco M, Matovic M, Balestreri L, et al: Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: A randomized controlled study based on serial venographies. Ann Oncol 20:1936-1942, 2009.
[4]. Garajova I., Nepoti G., Paragona M., Brandi G., Biasco G., Port-a-Cath related complications in 252 patients with solid tissue tumors and the first report of
heparin- induced delayed hypersensitivity after Port-a-Cath heparinisation, Eur J Cancer Care (Engl.), 2013, Jan;22(1):125-32
[5]. GUIDELINES FOR MAINTENANCE AND MANAGEMENT OF A PORTACATH, Nottingham University Hospitals, March 2012
[6]. Port Catheter Insertions, King Abdullag bin Abdulaziz, Arabic Health Encyclopedia, August 2011
[7]. Hadaway, L.C. (2010) Anatomy and Physiology Related to Infusion Therapy. In: Alexander,M.; Corrigan, A. Gorski, L. et al (eds) Infusion Nursing an Evidence Based Approach 3rd Edition: pp 137-177
[8]. Hayden BK and Goodman M (2005) Chemotherapy: principles of administration In: Henke Yar-bro, C. et al (eds) Cancer Nursing - Principles and Practice 6th Edition: pp 351-411
[9]. Jones and Bartlett London. Perucca, R. (2001). Obtaining Vascular Access. In: J. Hankin et al (eds) Infusion Therapy in Clinical Practice 2nd edition: pp 375-388. W.B. Saunders. Philadelphia.
[10]. Nishinari K1, Bernardi CV, Wolosker N, Yazbek G., Retained catheter: a rare complication associated with totally implantable venous ports, J Vasc Access. 2010 Apr-Jun;11(2):159-61
[11]. Shawn D Larson, Vascular Access Overview, Sep 04.2014
[12]. Stephen P. Povoski, Long- Term Central Venous Access, cancernetwork, Cancer Management, May 01, 2014
[13]. Karthaus M, Kretzschmar A, Kröning H, et al: Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: Final results of a double-blind, placebo-controlled phase III trial. Ann Oncol 17:289-296, 2006.
[14]. Verso M, Agnelli G, Bertoglio S, et al: Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: A double-blind, placebo-controlled, randomized study in cancer patients. J Clin Oncol 23:4057-4062, 2005.
MANAGING NAUSEA AND VOMITING IN CANCER PATIENTS -_LITERATURE REVIEW_
Sherbanov Ognyan
Medical Doctor, Philosophy Doctor, Chief assistent Ruse University ' 'Angel Kanchev ", Ruse, Bulgaria
Nedeva Teodora
Medical Doctor, Philosophy Doctor, Associate professor Ruse University ' 'Angel Kanchev ", Ruse, Bulgaria
SUMMARY
Treating nausea and vomiting in oncology patients, sometimes is challenging for the team. Cancer ill people should be assessed completely, the frequency, duration and intensity of nausea/vomiting should be estimated; patient's daily activities and the presence of anorexia and cachexia are also important facts. Another problem is whether nausea/vomiting are independent of cancer treatment or related to chemotherapy or radiation. The complications which are not related to treatment of cancer, are treated more successfully and specifically. For chemotherapy and radiation related nausea and emesis various national and international antiemetic guidelines are developed. Unfortunately the most prescribed antiemetics - dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine type 3 receptor antagonists - recommended in them, reduce significantly vomiting but not
nausea. Different randomized clinical trials have demonstrated that olanzapine is an effective agent either for prevention and treatment of chemotherapy induced nausea and vomiting. Many international guidelines are available. Particularly, the medical teams have difficulties with chronic nausea and vomiting in cancer patients. These complications are not related to the recent treatment with chemotherapy and/or radiation. Nausea and emesis in these patients may persist weeks after the treatment completion. The approach to this group of people is mainly empirical, based on personal experiences and clinical cases, because there are only a few studies available. Besides the data is of poor quality and most of the trials are uncontrolled.
Key words: antiemetics, cancer, chemotherapy, emesis, nausea, radiotherapy
УПРАВЛЕНИЕ ТОШНОТА И РВОТА В БОЛЬНЫХ РАКОМ -_ЛИТЕРАТУРНЫЙ ОБЗОР_
Шербанов Огнян
Врач, доктор по медицине, главный асистент Русенский университет "Ангел Кънчев', Русе, Болгария
Недева Теодора Врач, доктор по медицине, доцент Русенский университет"Ангел Кънчев", Русе, Болгария
АННОТАЦИЯ
Лечение тошноты и рвоты у пациентов с онкологией иногда является сложной задачей для команды. Раковые больные люди должны оцениваться полностью, необходимо оценить частоту, продолжительность и интенсивность тошноты / рвоты; ежедневные действия пациента и наличие анорексии и кахексии также являются важными фактами. Другая проблема заключается в том, что тошнота / рвота не зависят от лечения рака или связаны с химиотерапией или излучением. Осложнения, которые не связаны с лечением рака, рассматриваются более успешно и конкретно. Для химиотерапии и радиационной тошноты и рвоты разработаны различные национальные и международные противорвотные рекомендации. К сожалению, наиболее рекомендуемые в них рекомендуемые антагонисты рецепторов антиэмемики - дексаметазона, антагонистов нейрокинина-1, антагонисты 5-гидрокситриптамина типа 3, уменьшают значительную рвоту, но не тошноту. Различные рандомизированные клинические испытания показали, что оланзапин является эффективным средством для профилактики и лечения тошноты и рвоты, вызванной химиотерапией. Доступны многие международные руководящие принципы. В частности, медицинские бригады испытывают трудности с хронической тошнотой и рвотой у больных раком. Эти осложнения не связаны с недавним лечением химиотерапией и / или радиацией. Тошнота и рвота у этих пациентов могут сохраняться через несколько недель после завершения лечения. Подход к этой группе людей в основном эмпирический, основанный на личном опыте и клинических случаях, потому что доступно только несколько исследований. Кроме того, данные имеют низкое качество, и большинство испытаний неконтролируемы.
Ключевые слова: лучевая терапия, противорвотные средства, рак, рвота, тошнота, химиотерапия
INTRODUCTION:
The feeling of nausea and the act of vomiting are protective reflexes. In this way the stomach and intestines get rid of toxic substances. Nausea may be a prodromal phase to the act of emesis. [1,2,3] but not necessarily both processes are on a continuum. One may experience nausea without vomiting and vice versa. Emesis consists of pre- ejection phase, retching, ejection, shivering and salivation and is a conscious awareness of unusual sensation in the "vomiting center" of the brainstem. Nausea is queasy and sick sensation. [3, 32]
PRESENTATION:
The processes of nausea/vomiting are triggered when afferent impulses from the cerebral cortex, the chemoreceptor trigger zone located in the medulla, in the area postrema and fourth ventricle [3,4], the pharynx, the vagal afferent fibers of the gastrointestinal tract carry information to the vomiting center, located in the lateral reticular formation of the medulla. After that efferent impulses travel from the vomiting center to the salivation center, abdominal muscles, cranial nerves, respiratory center and cause vomiting. Mechanisms of
emesis are still not well defined. [3] Actually the studies for humans are based on studies in animals. [3,4] The main thought is that chemotherapeutic agents activate neurotransmitter receptors in the chemoreceptor trigger zone, the gastrointestinal tract and the vomiting center. So the goal in cancer patients is to identify the active neurotransmitters and their receptors in the CNS and in GI tract, that mediate the afferent impulses to the vomiting center and suppress them by the most suitable pharmacologic approach. The neurotransmitters involved in emesis are: GABA, acetylcholine, endorphins, histamine, dopamine, serotonin, substance P. [5] All agents that can block receptors for these transmitters in the chemoreceptor trigger zone, the vomiting center and the GI tract are very useful in preventing and controlling nausea and vomiting. The development of antagonists to substance P and serotonin receptors have very relative success in controlling emesis. These receptors are located either in the central nervous system or in peripheral areas, such as GI tract. But it is not clear whether these receptors are important in controlling nausea. Probably histaminic, dopaminergic and musca-rinic receptors play dominant role in nausea control.
[1,3,6,7] There are many studies and clinical trials concerning treatment related vomiting in oncology patients. These led to the creation of various number of antiemetic drugs. [1,2] At the same time most of these studies show that most doctor's efforts to prevent treatment- related nausea are not much effective. [3,6,7] only a few clinical trials resulted in successful treatment of nausea and vomiting caused by radiation and chemotherapy. [1,6,7]
Assessing patients with nausea and vomiting is recommended with using visual analog scale, with 10 points (with 0 signifying no nausea/vomiting and 10 is for maximal nausea/vomiting). Also the frequency; the daily activities such as use of medications, meals, exercises and the time of the day, should be carefully noted both for nausea and emesis. This is important for determining the severity and the context of both processes. When taking patient's history, inquiry regarding prescription or over-the-counter medications that may be responsible for nausea/vomiting is important. [8,9] Recent treatment with radiation or chemotherapy, and intake of potentially emetogenic drugs (antibiotics, opi-oids, selective serotonin reuptake inhibitors, non- ste-roidal anti-inflammatory drugs, oral iron) is necessary to be noted. [1] Another attention is recommendable for the possibility of organic causes of nausea/emesis, such as; inflammatory process, bowel obstructions, gastro-paresis; focal neurological signs, papilledema, elevated intracranial pressure, metastases in the central nervous system, vestibular dysfunction. [8] All these require physical examination including detailed assessment of the abdomen for tenderness or pain; neurologic examination; weight loss, appetite, cachexia, anorexia. This may provide insights into the possible etiology.
Cancer patients may have many reasons for nausea/vomiting and they are not always related with radiation and chemotherapy. The etiology may include; physiologic (brain metastases, gastritis, gastroesophageal reflux disease; dehydration); electrolyte disturbances (hyponatremia; hypercalcemia, gastroparesis, concurrent medications, bowel obstruction, vestibular dysfunction, chronic nausea, anorexia, malignant asci-tes, excessive secretions); behavioral (anxiety, depression, psychogenic nausea/vomiting,patient expectation of nausea). [10,11,12]
Conversely, many oncologic patients have chemotherapy-induced nausea and vomiting (CINV). The risk factors for CINV are 2 main groups: patient-related (previous episodes of CINV, female gender, age < 50 years, history of: pregnancy associated nausea and emesis, motion sickness, no or very limited alcohol intake) and treatment- related (chemotherapy dose, emetogenicity of cytotoxic regimen, rate and route of chemotherapy administration). The risk of CINV increases with the number of risk factors.
Some of the wee-known types of CINV are: anticipatory (feeling N/V prior to chemotherapy, conditioned response, occurs in 25% to 50 % of people); acute (occurs and resolves within 24h of therapy, as general peaks within 5 to 6 h); delayed (occurs 1 to 5 days after chemotherapy, common when administering cisplatin, carboplatin, doxorubicin, cyclophospha-
mide); breakthrough (occurs despite prophylactic treatment, may be acute or delayed, requires rescue therapy); refractory (occurs during chemotherapy cycle after prophylaxis and/or rescue therapy had failed in previous cycles). [1,2,11,13]
The antiemetic guidelines have specific recommendations for the antiemetic agents that should be used in preventing CINV. They are based on the emeto-genicity of the chemotherapeutic agent given. [11,13] The most prescribed and recommended pharmacologic agents for CINV are: olanzapine; corticosteroids; 5-HT3RA/NK1Ra combination - netupitant/palono-setron; neurokinin-1 receptor antagonists (NK1RAs) -aprepitant, netupitant,rolapitant; serotonin receptor an-tagonnists (5-HT3RAs) - ondansetron, granisetron, palonosetron, polymer- based granisetron)
For patients receiving highly emetogenic chemotherapy recommendations include usage of NK1RAs, 5-HT3RAs and dexamethasone and for those with moderate emetogenic chemotherapy - 5-HT3RAs or dexamethasone. All types of the mentioned above drugs, are successfully used in preventing vomiting in the majority of patients, but they are ineffective in nausea prevention. [1,2,6,7,14] Most clinical trials show that neither the substance P nor the serotonin receptors may have great importance in nausea mediation. Adding olanzapine to an antiemetic prophylactic regimen demonstrates good control of both nausea and vomiting in patients receiving moderate or highly emetogenic chemotherapy. [14,15] In many international guidelines this drug is recommended for CINV prevention in patients receiving highly emetogenic chemotherapy. [11,13]
Dexamethasone, metoclopramide, phenothiazines or olanzapine can effectively be prescribed in the treatment of breakthrough nausea/vomiting. [11] A 5-HT3RAs may also be effective, unless a patient presents with nausea and emesis that developed following the use of a 5-HT3RAs as prophylaxis for radiotherapy or chemotherapy induced emesis. The breakthrough nausea usually will not respond to an agent in the same drug class that has been used without success for prophylaxis. Patients who develop nausea/vomiting, 1 to 5 days after chemotherapy despite adequate prophylaxis, should be considered for 3 days regimen of treatment with sublingual or oral olanzapine or metoclo-pramide. Studies demonstrate that oral intake of 10mg/d olanzapine for 3days is significantly better than oral metoclopramide 10 mg for 3 days at controlling both emesis and nausea in patients receiving highly emetogenic chemotherapy who develop breakthrough CINV despite prophylactic antiemetics. [17]
NK1RAs are approved as additive agent along with 5-HTRAs and dexamethasone for CINV prevention. They are not recommended in breakthrough nausea and emesis treatment because they have not been studied yet.
Literature review demonstrates studies reporting complementary or alternative (use of ginger; acupuncture, acupressure ) therapeutic regimens for CINV prevention. The results are controversial. [11,16]
In refractory CINV adding benzodiazepines such as lorazepam or alprazolam to the regimen is advisory
especially in people in whom anxiety is considered a major factor in the CINV. [11,14,15]
In order to prevent the occurrence of anticipatory CINV: patients risk factors for CINV should be carefully evaluated; the most effective prophylactic antie-metic regimen for the patient's type of chemotherapy should be used prior to the first course of chemotherapy to obtain optimum control of CINV; patients should be counseled prior to the initial treatment of their expectations of nausea/vomiting connected with chemotherapy and should be informed that in 75% of people the prophylactic antiemetic regimen prescribed would have a complete response, ie no nausea, no emesis, no use of rescue medications. If the team manage to control CINV effectively in the first chemotherapy cycle, it is likely that the patient will have effective control during the subsequent cycles of the same chemotherapy. Conversely, if a patient has a poor experience with CINV in the first cycle, it may be more harder to control CINV in the subsequent cycles of chemotherapy. Thus anticipatory and/or refractory CINV may occur. To obtain on optimal outcome and prevent anticipatory CINV, the use of anti-anxiety medications (benzodiazepines) is recommended prior to the first course. But if anticipatory CINV appears despite the use of prophylactic an-tiemetics, behavioral therapy is considered. [18,19,20]
Literature review shows only a few randomized controlled clinical trials that have studied the prevention or treatment of radiotherapy associated nausea/vomiting. [25,26] Suggestions and recommendations vary a lot. The ASCO antiemetic guidelines [11] offer dexamethasone and 5-HT3 RAs for patients undergoing total body radiation and 5-HT3 RAs alone, for those who receive radiation to the upper abdomen.
Great challenge for the teams is the chronic nausea/vomiting in cancer patients unrelated to the recent treatment with chemotherapy and/or radiotherapy. It seems to be a particularly difficult clinical problem. Very often etiology of persistent nausea/emesis weeks after the treatment completion, is unknown. These may be patients of hospice, palliative care or with large tumors. The trials concerning this special category of people are with poor quality. [10,11,12] The approach to this group of patients is empirical, based on the personal experience or clinical cases of the medical team. The most often used antiemetics in this population of patients are: haloperidol; olanzapine; dexamethasone; prochlorperazine; metoclopramide; diphenhydramine; dronabinol and nabilone. They act on different receptors: dopamine, serotonine, histamine, mucscarinic, cannabinoid and have the following side effects, which medical team should have into consideration: akathisia; dystonia; prolonged QT interval; hypertension; dizziness; urinary retention; elevated blood glucose level; short-term sedation; psychoses; dysphoria; euphoria; hallucinations. [10,11,12]
CONCLUSIONS:
Complete assessment of nausea/vomiting in cancer patients should include the following: documentation of frequency, duration, intensity of nausea and/or emesis; associated activities; possible etiology; presence of cachexia or anorexia.
National and international antiemetic guidelines should be followed for the prevention of treatment- induced nausea and vomiting and for the treatment of established nausea and emesis.
NK1 RAs, 5-HT3RAs and dexamethasone have proven effect at preventing CINV. None of them is effective in nausea prevention. Adding olanzapine to a prophylactic regimen provides a very good control either of nausea or vomiting.
References: Список литературы:
[1]. Navari RM, Aapro M. Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;374:1356-67.
[2]. Navari RM. Management of chemotherapy-induced nausea and vomiting: focus on newer agents and new uses for older agents. Drugs. 2013;73:249-62.
[3]. Stern RM, Koch KL, Andrews PL. Nausea: mechanisms and management. New York: Oxford University Press; 2011.
[4]. Koga T, Fukuda H. Neurons in the nucleus of the solitary tract mediating inputs from vagal afferents and the area postrema in the pattern generator in the emetic act in dogs. Neurosci Res. 1992;14:366-79.
[5]. Bashashati M, McCallum RW. Neurochemical mechanisms and pharmacologic strategies in managing nausea and vomiting related to cyclic vomiting syndrome and other gastrointestinal disorders. Eur J Pharmacol. 2014;722:79-94.
[6]. Navari RM. Treatment of chemotherapy-induced nausea. Community Oncol. 2012;9:20-6.
[7]. Ng TL, Hutton B, Clemons M. Chemotherapy-induced nausea and vomiting: time for more emphasis on nausea? Oncologist. 2015;20:576-83.
[8]. Glare P, Miller J, Nikolova T, et al. Treating nausea and vomiting in palliative care: a review. Clin Intervent Aging. 2011;6:243-59.
[9]. Smith HS, Smith JM, Smith AR. An overview of nausea/vomiting in palliative medicine. Ann Palliat Med. 2012;1:103-14.
[10]. NCCN clinical practice guidelines in oncology. Palliative care. Version 1.2018; December 19,
2017. https://www.nccn.org/professionals/physician g ls/pdf/palliative.pdf. Accessed February 7, 2018.
[11]. NCCN clinical practice guidelines in oncology. Antiemesis. Version 2.2017; March 28, 2017. https://www.nccn.org/professionals/physician g ls/pdf/antiemesis.pdf. Accessed February 7, 2018.
[12]. Walsh D, Davis D, Ripamonti C, et al. 2016 updated MASCC/ESMO consensus recommendations: management of nausea and vomiting in advanced cancer patients. Support Care Cancer. 2017;25:333-40.
[13]. Molassiotis A, Aapro M, Herrstedt J, et al. MASCC/ESMO antiemetic guidelines: introduction to the 2016 guideline update. Support Care Cancer. 2017;25:267-9.
[14]. Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-
induced nausea and vomiting. N Engl J Med. 2016;375:134-42.
[15]. Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9:188-95.
[16]. Thamlikitkul L, Srimuninnimit V, Akewanlop C, et al. Efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving adriamycin-cyclophosphamide regimen: a randomized, doubleblind, placebo-controlled, crossover study. Support Care Cancer. 2017;25:459-64.
[17]. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy. Support Care Cancer. 2013;21:1655-63.
[18]. Navari RM. Should behavioral therapy be used as the primary treatment to control anticipatory vomiting? HemOnc Today. May 10, 2016. https://www.healio.com/hematology-oncology/breast-cancer/news/print/hemonc-today/%7Be07f26de-fdd7-40cd-96e0-68a49a6ba56f%7D/increased-awareness-new-therapies-may-alleviate-pervasive-problem-of-cinv?page=6. Accessed February 9, 2018.
[19]. Navari RM. Cancer patients at high risk for chemotherapy-induced nausea and vomiting— prediction assessments/tools. Expert Rev Quality Cancer Care. 2017;2:102-8.
[20]. Kamen C, Mohamedtaki A, Tejani KC, et al. Anticipatory nausea and vomiting due to chemotherapy. Eur J Pharmacol. 2014;722:172-9.
[21]. Schmitt T, Goldschmidt H, Neben K, et al. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol. 2014;32:3413-20.
[22]. Pielichowski W, Barzal J, Gawronski K, et al. A triple-drug combination to prevent nausea and vomiting following BEAM chemotherapy before
autologous hematopoietic stem cell transplantation. Transpl Proc. 2011;43:3107-10.
[23]. Stiff PJ, Fox-Geiman MP, Kiley K, et al. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013;19:49-55.
[24]. Svanberg A, Bergegard C. Addition of aprepitant to standard antiemetic regimen continued for 7 days after chemotherapy for stem cell transplantation provide significant reduction of vomiting. Oncology. 2015;89:31-6.
[25]. Dennis K, Rehana J, McGrath C, et al. A systematic review of methodologies, endpoints, and outcome measures in randomized trials of radiation therapy-induced nausea and vomiting. Support Care Cancer. 2017;25:2019-33.
[26]. Chiu N, Chiu L, Popovic M, et al. Latest advances in the management of radiation-induced pain flare, nausea and vomiting. Ann Palliat Med. 2016;5:50-7.
[27]. Digges M, Hussein A, Wilcock A, et al. Pharmacovigilance in hospice/palliative care: net effect of haloperidol for nausea and vomiting. J Palliat Med. 2018;21:37-43.
[28]. Prommer E. Olanzapine: palliative medicine update. Am J Hospice Palliat Med. 2012;30:75-82.
[29]. Jackson WC, Tavernier L. Olanzapine for intractable nausea in palliative care patients. J Palliat Med. 2003;6:251-5.
[30]. Kaneishi K, Kawabata M, Morita T. Olanzapine for the relief of nausea in patients with advanced cancer and incomplete bowel obstruction. J Pain Symptom Manage. 2012;44:604-7.
[31]. 31. Momani TG, Berry DL. Integrative therapeutic approaches for the management and control of nausea in children undergoing cancer treatment: a systematic review of literature. J Pediatr Oncol Nursing. 2017;34:173-84.
[32]. 32. Rudolph M. Navari, Managing Nausea and Vomiting in Patients With Cancer: What Works,2018, March 15; Vol. 32, Issue 3, Oncology Journal, www.cancernetwork.com
РЕЗЕКЦИЯ КАК МЕТОД ОПЕРАТИВНОГО ЛЕЧЕНИЯ БОЛЕЗНИ КРОНА
Стяжкина Светлана Николаевна
доктор медицинских наук, профессор, кафедра факультетской хирургии ФГБОУ «Ижевская государственная медицинская академия», г. Ижевск
Казакова Татьяна Анатольевна студент 4 курса лечебного факультета ФГБОУ «Ижевская государственная медицинская академия», г. Ижевск
Горбунова Елизавета Алексеевна студент 4 курса лечебного факультета ФГБОУ «Ижевская государственная медицинская академия», г. Ижевск
