CC BY
8
II. DIAGNOSTIC AND TREATMENT
ULTRASOUND DIAGNOSIS OF LIVERCYSTIC ECHINOCOCCOSIS, TREATMENT RESULTS
Barlybay R.A., Baimakhanov Zh.B., Enin E.A., Sadykov Ch.T., Kuttybaeva A.D., Erezhep A.E.
Department of Radiation Diagnostics,
A.N. Syzganov National Scientific Center of Surgery, Almaty, Kazakhstan
МРНТИ 76.29.62
Barlybay R.A. -
orcid.org/0000-0001-6079-4023
Baimakhanov Zh.B. -
orcid.org/0000-0003-1887-7866
Enin E.A. -
orcid.org/0000-0002-3101-6203
Sadykov Ch.T. -
orcid.org/0000-0001-5971-7821
Kuttybaeva A.D. -
orcid.org/0000-0003-2546-6387
Erezhep A.E. -
orcid.org/0000-0003-4253-5161
Abstract
Timely diagnosis of liver echinococcosis remains relevant to present. In order to improve the diagnosis and treatment of cystic echinococcosis of the liver, the WHO classification (2003) has been developed and introduced into practical medicine, which is used to make a diagnosis and choose a treatment. Ultrasound is a screening method that determines the further tactics of patient management. The ultrasound accuracy reaches 90%. The patients underwent various types of operations, depending on the stage of parasite development and the size of the cysts, and conservative treatment with albendazole was carried out.
Цистальщ бауыр эхинококкозыньщ ультрадыбыстьщ диагностикасы, емдеу нэтижeлepi
Барлыбай Р.А., Баймаханов Ж.Б., Енин Е.А., Садыков Ч.Т., Куттыбаева А.Д., Ережеп А.Е.
Сэулелi диагностика бeлiмшесi,
«А.Н. Сыз?анов атында?ы Улттык ?ылыми хирургиялык оргаль™» АК, Алматы, Казакстан
Keywords
ultrasonic diagnosis, liver, echinococcosis, classification, treatment, albendazole, pericystectomy
Ацдатпа
Бayыp эхинококкозын дер кез1нде aныктay бупнге дейiн eзектiлiгiн жойганжок. Цисталык бayыp эхинококкозын диaгноcтикaлay мен емдеyдi жaкcapтy максатында диагноз кою жэне емдеy эдiciн тaцдay ушн пайдаланылатын ДС¥ (2003ж.) классификациясы эзipлендi жэне практикалык медицинага енпзшд1. УДЗ - нayкacтapды бaкылayдын эpi карай€ы тактикасын айкындайтын скринингтк эдс. УДЗ-ныц накгылыты 90%-Fa жетедi. Кисталардыц eлшемi мен паразиттердщ дaмy сатысына байланысты нayкacтapFa тYpлi операциялар жасалды жэне альбендазол аркылы консервативлк ем журп'зmi.
Туйш свздер
yльтpaдыбыcтык диагностика, бayыp, эхинококкоз, классификация, smsy, альбендазол, перицистэктомия
Ультразвуковая диагностика цистного эхинококкоза печени, результаты лечения
Барлыбай Р.А., Баймаханов Ж.Б., Енин Е.А., Садыков Ч.Т., Куттыбаева А.Д., Ережеп А.Е.
Отделение лучевой диагностики,
АО «Национальный научный центр хирургии им. А.Н. Сызганова», Алматы, Казахстан Аннотация
Своевременная диагностика эхинококкоза печени остаётся актуальной по настоящее время. Для улучшения диагностики и лечения цистного эхинококкоза печени разработана и внедрена в практическую медицину классификация В03(2003г.), которая используется для постановки диагноза и выбора лечения. УЗД - это скрининговый метод, который определяет дальнейшую тактику ведения пациентов. Точность УЗИ достигает 90%. Пациентам выполнены различные виды операций в зависимости от стадии развития паразита и размеров кист и проведено консервативное лечение альбендазолом.
Ключевые слова
ультразвуковая диагностика, печень, эхинококкоз, классификация, лечение, альбендазол, перицистэктомия
Table 1.
Cystic echinococcosis is a common zoonotic disease in Central Asian countries. The problem of parasitic liver diseases remains relevant to present. The many domestic and foreign authors are dedicat-edworks on this topic. Every year the number of cases does not tend to decrease. In endemic areas, the incidence of echinococcosis in humans reaches 50 per 100,000 inhabitants. In Kazakhstan, more than 800 cases of the disease are detected annually. The most common is liver damage (44-84%). In the early stages of the disease, diagnosis is difficult due to the absence of any symptoms on account of the cysts small size and their location in the depths of the organ. The current state in solving this problem is based on the WHO classification developed by the informal working group WHO-IWGE in 2003 on the basis of GharbiH.A. classification [1,5]. Its essence lies in the fact that, based on the echographic image of echinococcal cysts, a five stages parasite development classification has been developed.
Currently, in practical medicine, much attention is paid to the diagnosis and treatment of liver echi-nococcosis. The main highly informative methods for diagnosing echinococcal cysts of the liver are radiation methods (ultrasound, CT, MRI). Ultrasound is a screening method that determines the further tactics of patient management (subject to conservative or surgical treatment)[2,5]. Ultrasound accuracy reaches 90%, but it depends on the class of the device and the experience of the researcher.
Ultrasound reveals small cysts, which allows the patient to undergo conservative treatment with antiparasitic drugs. In addition, echography determines the number of cysts in the liver, the presence of complicated forms of echinococcal cysts (suppuration, breakthrough into the bile ducts, abdominal or pleural cavities), the cysts contents, the presence of a capsule, detachment of the chitinous membrane, the presence of calcifications in the capsule
or the contents of the cyst.
The main treatment method of cystic echinococcosis of the liver is surgical. However, this leads to disability of the working-age population. The developed classification made it possible to correct the treatment of this pathology[6].
Due to the asymptomatic course of the disease, cysts are encountered by chance during ultrasound and the imaging results are the basis for the diagnosis of cystic echinococcosis of the liver. Many authors notice that in the presence of calcification in the walls of the cyst, X-ray cystic echinococcosis can be detected in 30% of cases. Calcifications in the form of small hyperechoic inclusions in the contents of the cyst are well visualized on MRI[2,4]. On ultrasound, a calcified capsule is quite well determined, indicating the death of the parasitic cyst [3,5].The most informative for ultrasound are cysts at stages CE2, CE3a and CE3b, since there are pathognomonic signs that are characteristic only for parasitic cysts.
Ultrasoundis "the preferred imaging method due to its availability, lack of radiation and high resolution for diagnostics" as noted by some foreign authors. In addition, the method is widely used in interventional treatment (PAIR). The authors point to the crucial importance of ultrasound in assessing the response to CE treatment, especially in asymptomatic CE4 cysts and CE5 watch-and-wait tactics [4].
The approach to the treatment of CE largely depends on the degree of organ damage, the number of cysts, the presence of cystic-biliary fistulas, etc. as it is noted in the works of foreign authors. Currently, three treatment options are used: conservative, surgical, and percutaneous (minimally invasive). Medical treatment is recommended for inoperable cases (multiple lesions of the lungs, liver and peritoneum) in order to reduce pressure in cysts, the risk of recurrence in preoperative and pre-puncture cases. Contraindications to treatment
Gharbi WHO-IWGE Classification signs Stage
I CE1 Hydatid cyst / Simple cyst Active
III CE2 Multivesicular cyst with daughter vesicles and septa Active
II CE3a Liquid formation with exfoliated chitinous membrane Transitional
III CE3b Daughtervesiclesin solid matrix Transitional
IV CE4 Heterogeneous matrix cyst without daughter vesicles Inactive degenerative
V CE5 Hyperechoic cyst wall Inactive degenerative
Тable 2.
WHOClassification Recommended treatment
CE1 d<5cmABZ d>5cm PAIR+ABZ
CE2 Surgery +ABZ or Non-PAIR PT+ABZ
CE3a d<5cm ABZ d>5cm PAIR+ABZ
CE3b surgery +ABZ Non-PAIR PT+ABZ
CE4 and CE5 watching and waiting
with albendazole are large cysts, calcified cysts, early pregnancy, and liver disease.
Total cystectomy [7] is considered the most radical among the surgical methods. Stages CE4 and CE5 should be "watch and wait" followed by a dynamic ultrasound [3].
The WHO classification is used for diagnosis and treatment selection. Cysts d <5.0 cm (CE1 and CE3a) are treated with ABZ, PAIR + ABZ therapy is recommended for cysts with d> 5.0 cm. ABZ is recommended to be prescribed 4 days before the procedure and 1 month after.
111 patients with primary hepatic echinococcosis were examined by ultrasound and treated, a morphological study was performed in 40 patients operated on echinococcosis at A.N. Syzganov NSCS, in the framework of the STP project from 2017 to 2019. The age of the patients ranged from 18 to 60 years, the average age was 34.2. Ultrasound was performed on the expert class VisionA-vius (Hitachi) and Phillips IU 22 devices. According to the WHO classification, the patients were distributed as follows:
• CE 1 - single-chamber cyst with homogeneous contents and a capsule along the periphery - 51 patients;
• CE 2 - on the background of the maternal vesicle, single or multiple daughter cysts with an echogenic contour are determined, which give the cyst the appearance of a "honeycomb" -17 patients;
• CE 3a - on the background of a homogeneous cavity, a chitinous capsule detached along the perimeter is determined (partial or complete detachment) - 11 patients;
• CE 3b - daughter vesicles, fragments of the chitinous membrane and hypoechoic masses filling the space between them are determined on the background of the maternal cyst; There is a small amount of free fluid in the cavity of the cyst; there can be viable protoscolexes in it and on the membranes - 12 patients;
• CE 4 - dead echinococcal cyst, its cavity is filled with a homogeneous echogenic mass, its contours may be uneven due to lack of tension in the cyst, indistinct, with fragments of fibrous capsule along the periphery. A symptom of increased echo signals is observed behind such a cyst, which indicates a thick liquid content of the cyst and can serve as a differential diagnostic sign. All membranes are destroyed, the cyst is a "ball of wool". There are no daughter vesicles - 5 patients.
• CE 5 - dead echinococcal cyst, presented in the form of a calcified arcuate capsule with an intense acoustic shadow behind it. Contains no living protoscolex-3 patients.
CE 1 and CE 2 forms are active, CE3a and CE 3b are intermediate or transitional due to the fact
Fig. 1
Echinococcal cyst at stage CE1
-
p
I
Wi Bl
' *
Fig. 2
Echinococcal cyst at stage CE3a
Fig. 3
Echinococcal cyst at stage CE4
Fig. 4
Echinococcal cyst at stage CE5
that at this stage cysts can organize, shrink, become infected or lead to the appearance of daughter vesicles; CE 4 and CE 5 are inactive, represent a dead parasite.
Pathognomonic symptoms for an echinococcal cyst are daughter vesicles in the contents of the maternal cavity and a detached chitinous membrane, laid in the form of a "water lily". This classification allows to work out the tactics of managing patients with cystic echinococcosis: patients with cysts up to 5.0 cm in size, uncomplicated, single or multiple small, are subject to outpatient observation. Conservative treatment with antiparasitic drugs (albendazole) is carried out for patients with cysts at stages CE1, CE3a, as an initial therapy of CE2 and CE3bforms, with multiple small cysts, with a positive ELISA for echinococcosis and as antirelapse treatment in the postoperative period. With dynamic observation during ultrasound, changes in the structure of the cysts are noted in the form of a decrease in size, uneven contours due to a decrease in tension in the cyst, incomplete or complete detachment of the chitinous membrane, thickening of the cyst contents, the appearance of calcifications in the capsule, which indicates a transition to the CE3- CE4 and a positive response to treatment. Ultrasound for dynamic control was performed in 3-612 months. In the absence of changes in cysts and the appearance of complications, the question was decided in favor of surgical treatment. It should be noted that cysts at stages CE4 and CE5 (these are inanimate, inactive) were only subject to dynamic
Fig. 5
Echinococcal cyst after ABZ treatment, marginal detachment of the chitinous membrane is noted
Fig. 6
Dead echinococcal cyst after ALB treatment
observation for 5 years without albendazole and surgical treatment.
All patients underwent a complete clinicallabo-ratory and instrumental examination (ultrasound, CT and MRI).
In the ultrasound department, all patients were examined at the preoperative stage with a detailed description of the number of cysts, their localization by segments and lobes of the liver, the size and volume of the cysts, the nature of the contents, the presence of complications (breakthrough into the bile ducts, abdominal or pleural cavity, relation to large vessels). A single echinococcosis was observed in 63 patients (2017 - 18, 2018 - 31, 2019 - 14), multiple - in 28 patients (2017 - 15, 2018 - 6, 2019 - 7). There were no complicated forms of echi-nococcosis in the examined patients. The stage of echinococcal cysts developmentwas determined by the echographic image. Dynamic control was performed 3-6 days after the operation, 10 days after discharge, after 3-6-12-24 months. The state of the residual cavity was noted, the presence of effusion was determined and then its volume (decrease, increase, suppuration) and other postoperative complications were monitored.
Patients taking conservative treatment with al-bendazole were examined on an outpatient basis according to the schedule. This group included patients with CE1 stage cystic echinococcosis, the size of which did not exceed 5.0 cm. The cysts were localized in 4-1-2 segments, intimately adjacent to the wall of the gallbladder and the inferior vena cava. There was a transition of cysts at the stages of CE3a and CE4, after three months of taking the drug: marginal or complete detachment of the chi-tinous membrane was noted in two patients, after 6 months in 3 patients.
In two cases, daughter vesiclesappeared on the background of thick contents (CE3bstage). The size of the cysts tended to decrease in all patients, in single cases - insignificant (5%). After 6 months of observation, most cysts had heterogeneous contents, which contained a thin layer of liquid, a thick component, and fragments of the chitinous membrane. The contours of the cysts became uneven and the volume decreased (15%).After 12 months, the cysts were visualized as echogenic inclusions of small size with small calcifications along the contour and in the structure of the content (20%).
In 1 case of albendazole treatment, toxic liver damage was observed, which was detected by ultrasound in the form of hepatomegaly, a decrease in the echogenicity of the liver parenchyma, therefore the patient was hospitalized for conservative treatment.
Over a analysis period, patients who refused further participation were excluded; due to loss of
connection with the patient and due to patients' violation of the treatment and monitoring regimen.
The main tasks of the surgical intervention were radicalism, a decrease in the frequency of postoperative complications and relapses, and the duration of inpatient treatment. Depending on the size and location of the cysts, their number, the presence of complications, clear indications for the use of one or another method of operation were determined. Surgical treatment of echinococcosis includes three methods, depending on the completeness of removal of the fibrous capsule:
1) Removal of the elements of the echinococ-cal cyst leaving the fibrous capsule of the parasite (echinococcectomy).
2) Removal of the echinococcal cyst together with the fibrous capsule of the parasite (pericystec-tomy).
3) Removal of the echinococcal cyst by liver resection.
Liver resections are performed for large and multiple cysts that occupy the anatomical lobe of the liver.
In our Center, all patients with cystic echinococcosis were divided into 4 groups depending on the type of treatment performed.
• group 1 - patients who underwent pericystec-tomy with removal of the capsule and prescription of the antiparasitic drug Zentel (30)
• group 2 - patients who underwent pericystec-tomy without Zentel prescription (27)
• group 3 - patients who underwent echinococ-cectomy with leaving the fibrous capsule and prescribing Zentel (27)
• group 4 - patients who received conservative treatment with Zentel (20)
29 patients were observed after pericystectomy + Zentel. The echo picture of the liver was homogeneous in the majority of patients, a residual cavity in the form of an echogenic area of a linear shape was detected in 3 patients. In two cases (6.8%), traces of liquid were observed, which completely resolved during the control study.
Pericystectomy without Zentel administration in the postoperative period was performed in patients with cystic echinococcosis at the stage of large CE1, CE2, CE 3b and CE4. Control ultrasound was performed in 27 patients. After 6 months of observation, an echogenic zone of a linear shape without a liquid component (96.3%) was visualized in the liver tissue, with traces of liquid in 1 patient.
After echinococcectomy with leaving the fibrous capsule + Zentel, ultrasound was performed in 25 patients; after 6 months, 40% of patients underwent ultrasound. Among them 2 patients had an effusion in the subphrenic space (8%), in 5 patients (20%) an effusion was detected in the residual cav-
ity, while in one patient the effusion was of a heterogeneous nature with an admixture of echogenic suspension. In the majority of patients in the postoperative period, the wound surface was unremarkable. During ultrasound, in 1-3 months in 3 cases, the residual cavity was visualized as an echogenic area, single calcifications were determined in its walls. In 1 case, after 3 months of observation, the residual cavity had the appearance of an anechoic formation with pockets of irregular shape. After 6 months, the residual cavity increased in size, echo-genic inclusions appeared in the fluid, which was regarded as suppuration. The patient underwent puncture and drainage of the residual cavity under ultrasound control.
Morphological examination of the surgical material
Morphological examination was performed only on operated patients. The total number was 40 patients.
• group 1 (9 patients): echinococtomy with leaving the fibrous capsule
• group 2 (17 patients): pericystectomy + al-bendazole
• group 3 (14 patients): pericystectomy without albendazole
• group 4: albendazole: no material was taken.
Morphological examination of the fibrous capsule
and liver tissue presenting to the fibrous capsule.
Around the emerging echinococcus lavrocyst parasitizing in one organ or another of the intermediate hosta capsule is formed. E.V. Rudin and N.G. Nazarevsky (1981) [10] identified 4 main types of the fibrous capsules structure in echinococcosis, which reflect 4 phases ofcellular immunity development.
A morphological study of intraoperative material taken from 40 patients was carried out to determine the germ elements of the parasite (protoscolexes and acephalocysts) and their viability in the fibrous capsule and liver tissue presenting to the fibrous capsule.
5 cases were referred to the first phase, in the test material there is a pronounced necrosis of the underlying tissue, with a pronounced accumulation of macrophages. In the granulation tissue forming around the parasite, a pronounced macrophage-phage reaction was noted, with an admixture of a large number of lymphoid cells, eosinophils and single plasmacytes. Fibrilogenesis is poorly expressed.
15 cases were considered as the second phase: necrotic changes were moderate, there were single macrophages, rare eosinophilic leukocytes, there was a pronounced lymphoid-cell infiltration, represented by lymphocytes of different sizes and plasma cells. In the granulation tissue, a decrease and hardening of the walls of blood vessels was determined, a large number of epithelioid cells and fibro-
Fig. 7
Acephalocysts at different stages of development. HE stain x 100.
blasts located in the form of a "stockade". Excessive growth of coarse fibrous connective tissue with a predominance of collagen fibers was revealed.
5 cases were referred to the third phase, where the chitinous membranes were fragmented with a loss of lamination, coarse fibrous connective tissue with areas of hyalinosis was presented to the laminar membrane of the parasite, and there was focal infiltration on the periphery, mainly by small lymphocytes and plasma cells.
10 cases belonged to the fourth phase: the fibrous capsule was represented by hyalinized coarsely fibrous connective tissue with the presence of scattered single lymphocytes and plasma cells in the outer layers.
Morphological examination of the fibrous capsule showed that the first layer of the capsule, adjacent to the laminar membrane of the parasite, was represented by coarse fibrous connective tissue, the bundles of which were arranged concentrically. In some cases, there were areas of necrosis. The fields of coarse-fibrous connective tissue with pronounced hyalinosis were also noted.
The connective tissue of the second layer was located deeper, which was represented by loose connective tissue with extensive fields of hyalino-sis. Small blood vessels were observed between the bundles of collagen fibers. There were groups of hepatocytes embedded in connective tissue fibers.
Groups of hepatocytes located in the fibrous
capsule had pronounced signs of dystrophic changes, around them there was a large number of capillary vessels surrounded by lymphoid cells with an admixture of eosinophils.
The third layer of the fibrous capsule was presented to the liver tissue; it was represented by loose connective tissue with the presence of vessels, the walls of which were sharply thickened due to the proliferation of connective tissue, and in places obliterated.
In the first and second layers of the fibrous capsule, degeneratively altered protoscolexes were found, around which scanty round-cell infiltration was noted. In areas of hyalinosis, the elements of the parasite were not identified. In isolated cases, ovoid-shaped protoscolexes surrounded by a clear membrane with deposition of calcium salts were found in the necrotic areas of the capsule.
The liver tissue adjacent to the fibrous capsule was divided into three layers. In the first transitional layer between the fibrous capsule and the parenchyma of the liver, coarse fibrous connective tissue grew, squeezing the hepatocytes. Hepatocytes in this layer were reduced in size, with symptoms of dystrophic changes. Hepatocytes with dense dark cytoplasm and high glycogen content were detected, cells with light cytoplasm without glycogen were foundwhile PAS staining. In the second layer in the liver parenchyma, dilated full-blooded vessels, bile capillaries with sclerosed walls were noted. Hepatocytes had different shapes and were mainly enlarged with hy-perchromic nuclei, in which chromatin condensation was noted. Transparent small vacuoles were found in the cytoplasm of the liver cells, and the phenomena of perisinusoidal and pericellular fibrosis were observed. In the third layer in the liver tissue, there was a slight proliferation of connective tissue in the portal tracts and small foci of hypertrophied hepatocytes. This layer contains both light and dark hepatocytes containing a small amount of glycogen.
Thus, the morphological study of the fibrous capsule with the phenomena of necrosis, pronounced macrophage reaction and active collagen formation,
Fig.8
IF - study of linear and granular luminescence of IgG +++ in the first / second layers of the fibrous capsule and the vessel wall at the border of the fibrous capsule and liver tissue.
revealed the presence of echinococcus embryonic elements (protoscolex) in the necrotic areas of the fibrous capsule adjacent to the laminar membrane of the parasite. In the study fields, where the growth of coarse-fibrous tissue was noted, degeneratively altered protoscolexes and fragments of the laminar membrane were observed in the fibrous capsule. No parasite elements were found in areas of hyalinosis.
Therefore, the classification of cystic echi-nococcosis of the liver developed by the WHO
References
1. Gharbi HA, Hassine W, Brauner MW, Dupuch K. «Ultrasound examination of the hydatic liver»// Radiology. 1981;139:459-463.
2. Gianluca Marrone, Francesca Crino', Settimo Caruso, Giuseppe Mamone, Vincenzo Carollo, Mariapina Milazzo, Salvatore Gruttadauria, Angelo Luca, and Bruno Gridelli «Multidisciplinary imaging of liver hy-datidosis»// World Journal Gastroeneterol 2012, April 7; 18(13): 1438-1447
3. Memmet Mihmanli, Ufuk Oguz Idiz, Cemal Kaya, Uygar Demir, OzgurBostanci,Sinan Omeroglu, Emre Bozkurt «Current status of diagnosis and treatment of hepatic Echinococcosis»// World Journal Hepatol , 2016 October 8; 8(28): 1169-1181
4. Brunetti E et al. «Ultrasound and Cystic Echinococcosis» Ultrasound Int Open 2018; 4: E70-E78
5. Tina Pakala, Marco Molina, George Y.Wu «Hepatic Echinococcocal Cysts:A Review»//J Clin Transl Hepa-
working group helped to significantly improve the diagnosis of this pathology and develop tactics for managing this group of patients both in the preoperative and postoperative periods, which significantly improved the results of surgical treatment. A certain group of patients after successful conservative treatment with albendazole did not undergo surgical intervention, which ultimately made it possible to reduce the disability of the working-age population.
tol. 2016 Mar 28; 4(1): 39-46
6. Anand, Lt Col,S.Rajagopalan, Brig and Raj Mohan «Management of liver hydatid cysts-Current perspectives»
7. Namita Bhutani, Pradeep Kajal «Hepatic echinococcosis^ review»// Ann Med Surg (Lond). 2018 Dec; 36: 99-105
8. Sh.Sh. Amonov, D.A. Rakhmonov et al. "Modern aspects of the diagnosis of surgical treatment of liver echinococcosis" // Bulletin of Avicenna, v.21, N3, 2019.(in Russian)
9. Lotov N.N., Zhao A.V., Black N.V. "Echinococcosis: diagnosis and modern methods of treatment" // Clinical medicine N2 / 10,18-26. (in Russian)
10. E.V.Rudina,N.G.Nazarevsky «Formation of the parasite capsule and the reaction of surrounding tissues in echinococcosis». // Medical parasitology and parasitic diseases, 1981.-№5- C. 18-21.
