Американский Научный Журнал PROSPECTS FOR NEOADJUVANT TREATMENT OF AMPULLARY CANCER (28-36)

Objective: to study the possibilities of preoperative radiation therapy in a radical treatment regimen for glandular ampullary cancer. Materials and methods. In 2001-2019, 21 cases of pancreatic-biliary type of ampullary cancer underwent radical treatment, including preoperative RT, extended GPDR and adjuvant chemotherapy according to indications (experimental group), 48 cases of pancreatic-biliary type of ampullary cancer underwent expanded GPDR and adjuvant chemotherapy according to indications (control group), and 43 cases of intestinal type of ampullary cancer underwent extended GPDR and adjuvant chemotherapy according to indications. Results. Radiation therapy caused radiation injuries in 28.6% of patients: grade 1 erythema (19.1%), grade 1 leukopenia (4.75%), and grade 2 leukopenia (4.75%). Postoperative complications, mortality of the experimental group and the control group, respectively, amounted to 28.6% and 50.0% (p = 0.09) and 4.8% and 6.3% (p = 0.8). The overall 5-year survival rate, the average life expectancy of the experimental group and the control group, respectively, were 50.7% and 9.8% (p = 0.01) and 74.8 ± 12.58 months and 21.7 ± 6.11 months (p = 0.0008). The overall 5-year survival rate, the average life expectancy of the group with intestinal ampullary cancer, were 61.3% and 60.5 ± 9.15 months, respectively. Relapse-free survival of patients with glandular ampullary cancer (n = 112) who received treatment according to the radical regimen was: 1-year - 77.8%, 3-year - 51.0%, 5-year - 35.2%, average life expectancy - 44.7 ± 5.44 months Conclusion. Radiation injuries were stopped by conservative measures and did not increase the duration of the preoperative period. Preoperative RT in the radical treatment regimen for pancreatic-biliary type of ampullary cancer neither changed the nature nor increased the incidence of postoperative complications. Combined treatment significantly improved long-term survival in cases with pancreatic-biliary type of ampullary cancer. Скачать в формате PDF
28 American Scientific Journal № ( 41) / 2020
PROSPECTS FOR NEOADJUVANT TREATME NT OF AMPULLARY CANCER

Rasulov R.I. 1,
Dvornichenko V.V. 1,2,
Nazarova D.V. 2,
Nurbekian G. V.2 1Department of Oncology,
Branch of the Russian Medical Academy of Continuing Professional Education,
Ministry of Health of the Russian Federation,
64049, Irkutsk, Yubileiny microdistrict, 100. 2SBHI "Regional Oncological Dispensary", 664035, Irkutsk, Frunze str., 32
DOI: 10.31618/asj.2707 -9864.2020.3.41.34
Abstract . Objective: to study the possibilities of preoperative radiation therapy in a radical treatment regimen
for glandular ampullary can cer.
Materials and methods. In 2001 -2019, 21 ca ses of pancreatic -biliary type of ampullary cancer u nderwent
radical treatment, including preoperative RT, extended GPDR and adjuvant chemotherapy according to indications
(experimental group), 48 cases of pan creatic -biliary type of ampullary cancer underw ent expanded GPDR and
adjuvant chemotherapy accordin g to indications (control group), and 43 cases of intestinal type of ampullary
cancer underwent extended GPDR and adjuvant chemotherapy according to indicati ons.
Results. Radiation therapy caused radiatio n injuries in 28.6% of patients: grade 1 erythema (1 9.1%), grade 1
leukopenia (4.75%), and grade 2 leukopenia (4.75%). Postoperative complications, mortality of the experimental
group and the control group, re spectively, amounted to 28.6% and 50.0% (p = 0. 09) and 4.8% and 6.3% (p = 0.8).
The overall 5 -year survival rate, the average life expectancy of the experimental group and the control group,
respectively, were 50.7% and 9.8% (p = 0.01) and 74.8 ± 12.58 mon ths and 21.7 ± 6.11 months (p = 0.0008). The
ov erall 5 -year survival rate, the average life expecta ncy of the group with intestinal ampullary cancer, were 61.3%
and 60.5 ± 9.15 months, respectively. Relapse -free survival of patients with glandular ampullar y cancer (n = 112)
who received treatment accor ding to the radical regimen was: 1 -year - 77.8%, 3 -year - 51.0%, 5 -year - 35.2%,
average life expectancy - 44.7 ± 5.44 months
Conclusion. Radiation injuries were stopped by conservative measures and did not in crease the duration of
the preoperative period. Preoperative RT in the radical treatment regimen fo r pancreatic -biliary type of ampullary
cancer neither changed the nature nor increased the incidence of postoperative complications. Combined treatment
signi ficantly improved long -term survival in cases w ith pancreatic -biliary type of ampullary cancer.
Key words : ampullary cancer, pancreatic -biliary type, preoperative radiation therapy.

Information about authors
Rodion Ismagilovich Rasulov - Ph.D. Medicine, Professor, Professor of the Department of Oncology, Branch
of the Russian Medical Academy of Continu ing Professional Education, Ministry of Health of the Russian
Federa tion.
Viktoriia Vladimirovna Dvornichenko - Ph.D. Medicine, Professor, Head of the Department of Oncology,
Branch of the Russian Medical Academy of Contin uing Professional Education, Minis try of Health of the Russian
Federation, Chief Physician of SBHI “Re gional Oncological Dispensary”.
Daria Vladimirovna Nazarova - senior resident of the oncology unit No. 7 of SBHI “Regional Oncological
Dispensary”.
Grigor ii Valerievich Nurbekian - residen t physician of oncology unit No. 7 of SBHI “Regional Oncological
Dis pensary”.
For correspondence: Rodion Ismagilovich Rasulov
Address: 32 Frunze Street, Irkutsk, 664035
tel.: 89246209670

Introduction
Treatment of cancer of the ampulla of Vater is one
of the most complex and yet unresolved problems in
oncology. Many tactical and technical issues have
remained controversial and far from being addressed.
Currently, the range radical surgical techniques is
represented by transduodenal papillectomy and
pancre atoduodenal resection (PDR). The indications
for transduodenal papillectomy are strictly limited.
This range of surgical aid is an alternative in the
surgeon's arsenal for patients with severe concomitant
pathology, which excludes the use of PDR.
The surgi cal standard for treatment of ampullary
cancer remains PDR with lymphadenectomy.
Postoperative complications account for 22 -67%,
mortality – 0-9% [ 1, 2, 3]. Overall survival in
observations where the R0 operation was performed:
median - 30.1 -113 months, 1 -year - 75-86.7%, 3 -year -
57.3 -69.4%, 5 -year - 20 -88% [ 4, 5, 6, 7, 8 ].
To improve long -term results, radical surgery
should be integrated into multimoda l treatment.
Currently, the data on the effectiveness of the use
of adjuvant therapy in the radical regi men for the
treatment of ampullary cancer are contradictory. A
number of fairly large studies have shown that adjuvant
therapy did not improve long -term treatment results. In
particular, clinical studies of ESPAC -1 (1997) and
EORTC (1999) of pancreatic hea d cancer and

American Scientific Journal № ( 41) / 2020 29

periampullary cancer did not reveal the effectiveness of
adjuvant chemoradiation therapy (CRT) [ 9, 10 ]. As a
result, the role of CRT in the radical treatment of
pancreatic head cancer requires clarification. I. Nassour
et al. (2018) noted that in 2004 -2013 the treatment of
pancreatic head cancer made a shift from adjuvant
chemotherapy to chemotherapy (CT), which increased
from 9% to 32%. Howe ver, adjuvant chemotherapy in
periampullary cancer in the ESPAC -3 study (2012),
and in ampullary cancer in the ESPAC -3 study (v2,
2016) did not increase life expectancy [ 12, 13 ].
Subsequently, Z. Jin et al. (2018), M. Al -Jumayli et al.
(2019), B.L. Ecker e t al. (2019) did not find a
significant increase in long -term survival of patients
with ampullary cancer receiving adjuvant treatment.
According to other studies, adjuvant therapy is a
promising direction in the combination treatment of
ampullary cancer. A meta -analysis of ten retrospective
studies, including 3361 observations, showed that
adjuvant chemorad iotherapy was associated with a
lower risk of death (HR = 0.75; P = 0.001) compared to
surgery alone [ 17 ]. Analysis of a large sample of
NCDB (National Cancer Database) showed that
adjuvant chemotherapy significantly increased life
expectancy in the group with the T3/T4 index, and
adjuvant chemotherapy significantly increased life
expectancy in the group with metastatic lymph node
lesions [ 11 ].
Thus, ther e are still no randomized controlled
trials proving the effectiveness of adjuvant
chemotherapy and radia tion therapy (RT) for ampullary
cancer. Until now, neither the national clinical
guidelines, nor the recommendations of RUSSCO,
ESMO, NCCN provide indic ations and modes of
adjuvant chemotherapy in the program of radical
treatment of ampullary cancer.
Rando mized controlled trials on the neoadjuvant
treatment of ampullary cancer are also absent. There is
no definitive consensus recommendation for the use of
neoadjuvant chemotherapy and radiotherapy for
ampullary cancer; in general, treatment is
individualized and/or based on regional inpatient
protocols.
In conclusion, the issue of neoadjuvant treatment
of ampullary cancer remains open. The issue of
adjuvan t treatment of ampullary cancer has not yet been
closed (there are no indications and regimens for
adjuv ant chemotherapy), and morphological
heterogeneity of ampullary cancer determines a large
spread in long -term survival rates (5 -year from 20% to
88%), w hich requires the study of prognostic factors,
considering the latter, and the development of radical
treatment regimens.
Objective: to study the possibilities of
preoperative radiation therapy in a radical treatment
regimen for glandular ampullary cancer .
Materials and methods
In 2001 -2019, 116 patients with glandular
ampullary cancer received treatment in the Irkutsk
Regional Oncological Dispensary. Of these, 63
(54.3%) were men and 53 (45.7%) - women. Most of
the patients were aged 51 -70 years (86 - 74.1%); the
average age was 59.1 ± 0.83 years (Table 1).
Table 1
Grouping by sex and age
age sex total me n women
30-40 2 (1.7%) - 2 (1.7%)
41-50 10 (8.6%) 7 (6.0%) 17 (14.7%)
51-60 27 (23.3%) 17 (14.7%) 44 (37.9%)
61-70 21 (18.1%) 21 (18.1%) 42 (36.2%)
over 70 3 (2.6%) 8 (6.9%) 11 (9.5%)
63 (54.3%) 53 (45.7%) 116 (100%)
total 116 (100%)

Ninety -one (78.4%) of 116 patients with
ampullary cancer were admitted to the dispensary with
obstructive jaundice. At the pre -specialized stage, the
following bile diversion techniques were performed:
cholecystostomy by projection access - 12 (13.2%),
laparoscopi c cholecystostomy - 15 (16.5%),
endoscopic stenting of extrahepatic bile ducts - 44
(48.3%), external drainage of the common bile duct - 7
(7.7%), formation of biliodigestive anastomoses - 4
(4.4%), cholecystostom y under ultrasound navigation -
1 (1.1%), a nd endoscopic papillosphincterotomy - 8
(8.8%) cases.
At the diagnostic stage, pancreatobiliary type of
cancer was found in 71 (61.2%) cases, and intestinal
type of cancer in 45 (38.8%) cases.
Grouping of the pati ents by morphology and stage
of the tumor p rocess is shown in Table 2.

30 American Scientific Journal № ( 41) / 2020
Table 2
Grouping of the patients by morphology and stage of the tumor process
signs pancreato -biliary type intestinal type total
1. stage of the tumor process
- IA 9 (12.7%) 8 (17.8%) 17 (14.7%)
- IB 10 (14.1%) 10 (22.2 %) 20 (17.2%)
- IIA 12 (16.9%) 6 (13.3%) 18 (15.5%)
- IIB 17 (23.9%) 6 (13.3%) 23 (19.8%)
- III 2 (2.8%) 6 (13.3%) 8 (6.9%)
- IV 21 (29.6%) 9 (20.0%) 30 (25.9%)
total 71 (100%) 45 (100%) 116 (100%)
2. tumor differentiation degree
- severe 5 (7.0%) 22 (48.9%) 27 (23.3%)
- moderate 53 (74.7%) 17 (37.8%) 70 (60.3%)
- low 13 (18.3%) 6 (13.3%) 19 (16.4%)
total 71 (100%) 45 (100%) 116 (100%)

Stage II of the tumor process (40.8%) and a
moderate degree of tumor differentiation (74.7%)
prevail ed in the pancreatic -biliary type of ampullary
cancer. In the intestinal type, stage I of the tumor
process (40.0%) and severe tumor differentiation
(48.9%) prevailed.
In the structure of ampullary cancer, stage I was in
31.9% of cases, stage II - 35.3%, s tage III - 6.9%, and
stage IV - 25.9%. Severe tumor differentiation was
found in 23.3% of cases, moderate - in 60.3% and low
- in 16.4%.
Sixty -nine of 71 c ases of pancreatic -biliary type of
ampullary cancer received radical treatment; in 2 cases
during th e operation, metastatic lesions of the liver and
carcinomatosis of the abdominal cavity were detected.
Forty -three of 45 cases of intestinal ampullary cance r
received radical treatment; in 2 cases during the
operation, metastatic lesions of the liver and
carcinomatosis of the abdominal cavity were detected.
In 21 cases of the pancreatic -biliary type,
treatment was started with remote RT (main group), in
48 (c ontrol group) - with radical surgery.
Remote RT was started 4 weeks after biliary
decompression. Top ometry was performed on a
multispiral computed tomograph. For better
visualization of the tumor and a landmark, X -ray
contrast marks were applied, and the i ntroduction of a
X-ray contrast agent was also used. Computed
tomograms were performed with an inter val of 2.5 -5
mm, with the scanning level from the upper edge of the
liver Th10 -11 to L3 -4. The second stage was the
contouring of the scans obtained as a re sult of
topometry. Planning and dosimetric calculations were
performed on a 3 -dimensional planning s ystem
"Eclipse" (3D) with the exclusion of critical organs
(kidney, spinal cord, liver, spleen, small intestine) from
the irradiation zone. RT was performed using the
classical mode of fractionation ROD -2Gy 5 times a
week to SOD -50Gy for 5 weeks.
In 112 (9 6.5%) cases, a radical volume of the
operative manual was completed (Table 3). This group
included 21 observations, where treatment was started
with remote RT and 91 observations, where treatment
was started with radical surgery.
Table 3
Grouping of pati ents by the extent of surgical aid
extent of surgical intervention number
extended gastropancreatoduodenal resection
+ right hepatic artery resection
total
91 (78.4%)
1 (0.9%)
92 (79.3%)
extended gastropancreatoduodenal resection with mesenteric -portal venous segment resection
+ right hepatic artery resection
total
12 (10.3%)
1 (0.9%)
13 (11.2%)
total pancreatoduodenal ectomy 5 (4.3%)
transduodenal papillectomy 2 (1.7%)
explorative laparotomy 3 (2.6%)
hepaticojejunostomy, gastrojejunostomy 1 (0.9%)
total 116 (100%)

Ninety -one (78.4%) cases underwent extended
gastropancreatoduodenal resection (GPDR) , 12
(10.3%) cases - extended GPDR with resection of the
mesenteric -portal venous segment (MPVS), 1 (0.9%) -
expanded GPDR with resection of the right hep atic
artery, 1 (0.9%) - extended GPDR with resection of the
MPVS and the right hepatic artery, 5 (4.3% ) - total
duodenpancreatectomy, 2 (1.7%) - transduodenal
papillectomy, in 3 (2.6%) - trial laparotomy, and 1
(0.9%) - hepaticojejunostomy, gastrojejuno sto my.
Currently, neither the national clinical guidelines,
nor the recommendations of RUSSCO, ESMO, NCC N
provide indications and modes of adjuvant
chemotherapy in the program of radical treatment of
ampullary cancer. Therefore, in order to determine the
ind ications for adjuvant chemotherapy, the relationship

American Scientific Journal № ( 41) / 2020 31

between long -term survival and morphological feat ures
was studied. Based on the data obtained, the indications
for adjuvant chemotherapy were determined: the
growth of the ampullary tumor into the pan cre as head,
metastatic lesions of regional or juxta -regional lymph
nodes, the presence of tumor emboli in the lymphatic
or blood vessels. Based on the results of the ESPAC -3
study, Mayo regimen and gemcitabine monotherapy
were adopted as medication regimen s.
Four -six weeks after radical surgery, the following
chemotherapy regimens were used: in 17 cases - May o
regimen (5 -fluorouracil 425 mg / m2 i.v., jet +
leucovorin 20 mg/m 2 i.v., jet, on the 1st - 5th days of
the 28 -day cycle, 6 cycles), in 30 cases - mo not herapy
with gemcitabine (1000 mg/m 2 on the 1st, 8th, 15th day
with a break of 2 weeks, 4 -6 courses).
Results
To assess the neoadjuvant treatment of pancreatic -
biliary ampullary cancer, patients were grouped as
follows – experimental group (n = 21) or co ntrol group
(n = 48). In the experimental group, combined
treatment was carried out, including preopera tive
remote RT, extended GPDR and adjuvant
chemotherapy according to indications. In the control
group, extended GPDR and adjuvant chemotherapy
were perf ormed according to indications. The groups
studied postoperative complications, mortality, overall
surv ival, average life expectancy.
The analysis of the studied groups showed no
significant differences: sex (p = 0.5) and age (p = 0.6)
distribution of pati ents, ECOG functional state (p =
0.8), ASA physical status (p = 0.3), the stage of the
tumor process (p > 0.05), the extent of surgical aid (p>
0.05), the type of anastomosis between the pancreas
stump and the intestinal tube (p> 0.05), the duration of
the operation (p = 0.9), intraoperative blood loss (p =
0.9), regimens of adjuvant chemotherapy (p = 0.9), i.e.
the studied groups are identical.
In the experimental group, at the stage of RT,
radiation injuries occurred in 6 (28.6%) cases:
erythema in 4 (19.1 %) cases, and leukopenia in 2
(9.5%) cases. Considering the table of acute radiation
injuries (RTOG, 1995), grade 1 erythema was
determined in all 4 cases. On average, erythema
occurred on day 20.9 ± 1.84 (14 -32) from the start of
RT. To relieve itching an d inflammation, the area of
radiation damage was treated with mild steroid creams.
On average, erythema disappeared without skin
pigmentation in 6.8 ± 0.61 (4 -10) days after the end of
RT. Leukopenia developed in 2 cases at the RT stage.
Considering the ta ble of acute radiation injuries
(RTOG, 1995), grade 1 leukopenia and grade 2
leukopenia were e stablished in 1 case. Grade 1
leukopenia developed during the first sessions of
external RT and persisted throughout the entire course
of RT. This leukopenia was no t specifically corrected.
Grade 2 leukopenia developed after the fourth RT
session. In order to correct leukopenia, a single
injection of prednisolone 30 mg intramuscularly was
performed. There was a positive dynamics and
recovery of leukocytes within th e laboratory norm
before discharge (one day after the end of RT).
Postoperative complications in the groups are
presented in Table 4.
Table 4
Postoperative complications in the groups
postoperative complications based on the
Clavien -Dindo grades
experimen tal
group, n=21
control group,
n=48
intestinal type,
n=43 total, n=112
grade I
- wound suppuration - - 1 (2.33%) 1 (0.9%)
- hemorrhagic gastritis - - 1 (2.33%) 1 (0.9%)
- bilateral pneumonia - - 1 (2.33%) 1 (0.9%)
grade IIIa
- pancreatic fist ula , class A according to ISGPF 3 (14.3%) 7 (14.6%) 5 (11.6%) 15 (13.4%)
- pancreatic fistula, class AB according to
ISGPF - 3 (6.3%) 2 (4.65%) 5 (4.4%)
- liver abscess - 1 (2.08%) - 1 (0.9%)
- abscess of the abdominal cavity 2 (9.5%) - 1 (2.33%) 3 (2.7 %)
p=0.9
grade IIIb
- pancreatic fistula, class AC according to
ISGPF - 1 (2.08%) - 1 (0.9%)
- hepaticojejunostomy failure - - 1 (2.33%) 1 (0.9%)
- bilious peritonitis - 1 (2.08%) - 1 (0.9%)
- perforation of the small intestine - - 1 (2.33%) 1 (0.9%)
- acute intestinal obstruction - 1 (2.08%) - 1 (0.9%)
- biliary fistula - 1 (2.08%) - 1 (0.9%)
- abscess of the abdominal cavity - 1 (2.08%) - 1 (0.9%)
- subcutaneous eventration - - 1 (2.33%) 1 (0.9%)
p=0.1
grade IVa
- arrosive bleed ing - 3 (6.3%) 1 (2.33%) 4 (3.6%)
- intra -abdominal bleeding - 1 (2.08%) - 1 (0.9%)
- TELA - 1 (2.08%) - 1 (0.9%)

32 American Scientific Journal № ( 41) / 2020
p=0.1
grade V
- arrosive bleeding 1 (4.8%) - 1 (2.33%) 2 (1.8%)
- postoperative peritonitis - 3 (6.3%) 2 (4.65%) 5 (4.4%)
p=0.8
total 6 (28.6%) 24 (50.0%) 18 (41.9%) 48 (42.9%)
p=0.09

A retrospective analysis of the immediate results
of surgical treatment of the main group and the group
of clinical comparison showed that postoperative
complications occurred in 6 (28.6%) and 24 (50.0%)
cases, respectively.
Postoperative complications in the experimental
group and control group were distributed as follows:
grade IIIa complications, respectively 5 (23.8%) and 11
(22.9%; p = 0.9), grade IIIb complications - 0 and 5
(10.4 %; p = 0.1), grade IVa co mplications - 0 and 5
(10.4%; p = 0.1), grade V complications - 1 (4.8%) and
3 (6.3%; p = 0.8) observations. There were no
significant differences in the structure and frequency of
postoperative complications of the studied groups (p =
0.09).
Forty -eight ( 42.9%) of 112 cases radically
operated for ampullary cancer developed complications
(Table 4). Analysis of the structure of postoperative
complications showed that in the overwhelming
majority they are represented by evasion of pancre atic
secretion from th e zone of pancreatojejunoanastomosis
and complications arising against the background of
this evasion - pancreatic fistula (18.7%), arrosive
bleeding (5.4%), postoperative peritonitis (4.4%) and
abdominal abscesses (3.6%).
A retrospec tive analysis of the i mmediate results
of surgical treatment of the main group and the group
of clinical comparison showed that mortality in the
study groups was 4.8% (1 case) and 6.3% (3 cases, p =
0.8), respectively.
The causes of deaths in the groups ar e pr esented
in Table 5 .
Table 5
The causes of deaths in the groups
Cause of death experimental
group, n=21
control group,
n=48
intestinal type,
n=43 total, n=112
hemorrhagic shock 1 (4.8%) - 1 (2.3%) 2 (1.8%)
multiple organ failure - 3 (6.3%) 2 (4.7%) 5 (4.4 %)
total 1 (4.8%) 3 (6.3%) 3 (7.0%) 7 (6.2%)
p=0.8

Seven (6.2%) of 112 cases radically operated for
ampullary cancer died.
In 2 (1.8%) cases, the cause of death was
hemorrhagic shock against the background of arrosive
bleeding. Of these, in 1 case a rrosion of the splenic
artery wall was established and in 1 case - the left
gastric artery. In 5 (4.4%) cases, the cause of death was
multiple organ failure associated with postoperative
peritonitis. Of these, in 3 cases, the cause of
postoperative p eriton itis was pancreatic fistula of class
C according to ISGPF and in 2 cases - recurrent
perforation of the intestinal tube.
The overa ll survival rate of the groups is shown in
Table 6.
Table 6
The overall survival rate of the groups
survival intestinal type experimental
group р control group ductal pancreatic head
cancer, data of IROD*
1 year 100% 94.2% 0.004 51.9% 51.8%
2 years 93.3% 88.3% <0.001 23.0% 19.8%
3 years 81.9% 82.2% <0.001 13.1% 14.4%
5 years 61.3% 50.7% 0.01 9.8% 5.2%
7 years 42.5% 44.4% 0.0 1 6.5% 5.2%
10 years 42.5% 35.5% 0.05 6.5% 2.6%
average survival, months 60.5±9.15 74.8±12.58 0.0008 21.7±6.11 15.5±1.65
Note: * - data of the clinical material of the Irkutsk Regional Oncological Dispensary for 2006 -2016 published in
Practical O ncology . 2018; 19(4): 408 -418. doi: 10.31917/1903408

Table 6 includes column No. 6 (in dark) with long -
term survival ra tes for ductal cancer of the pancreas
head (operable observations, where extended GPDR
and adjuvant chemotherapy were performed).
The overall survival of the experimental and
control group, respectively, was: 1 year - 94.2% and
51.9% (p = 0.004), 2 year - 88.3% and 23.0% (p
<0.001), 3 year - 82.2% and 13.1% (p <0.001), 5 year -
50.7% and 9.8% (p = 0.01), 7 year - 44.4% and 6.5% (p
= 0.01 ), 10 ye ar - 35.5% and 6.5% (p = 0.05), average
life expectancy - 74.8 ± 12.58 months and 21.7 ± 6.11
months (p = 0.0008) .
A notable fact is that the traditional treatment
regimen (radical surgery and adjuvant chemotherapy

American Scientific Journal № ( 41) / 2020 33

according to indications) in pati ents wit h pancreatic -
biliary type of ampullary cancer (control group)
showed unsatisfactory long -term survival results,
which are almost identical to the long -term survival
results in pancreatic ductal cancer (see Table 6). The
inclusion of preoperative ra diation therapy in the
radical treatment regimen made it possible to
significantly increase the long -term survival rate i n
pancreatic -biliary type of ampullary cancer
(experimental group), which became commensurate
with the long -term survival rate of radic ally tre ated
intestinal type of ampullary cancer.
Relapse -free survival of patients with glandular
ampullary cancer (n = 112) who received radical
treatment in 2001 -2019 in the Irkutsk Regional
Oncological Dispensary is presented in Table 7.
Table 7.
Relapse -free survival of patients with glandular ampullary cancer who received radical treatment
in 2001 -2019.
survival Stage I Stage II Stage III Stage IV All stages
1 year 90.0% 78.2% 81.9% 60.0% 77.8%
2 years 86.4% 57.8% 54.6% 23.5% 59.1%
3 years 78. 7% 46.2% 54.6% 17.6% 51.0%
5 years 59.0% 33.7% 54.6% 0 35.2%
7 years 43.3% 33.7% 27.2% 0 27.4%
10 years 43.3% 33.7% 0 0 25.6%
average survival, months 79.2±11.86 37.7±7.37 28.2±15.20 14.5±4.89 44.7±5.44
Relapse -free survival was: 1 year - 77.8%, 2 yea rs - 59.1 %, 3 years - 51.0%, 5 years - 35.2%, 7 years - 27.4%,
10 years - 25.6%, average life expectancy - 44.7 ± 5.44 months.

Discussion
Ampullary cancer is a relatively rare
heterogeneous malignant neoplasm, occurs in 6 cases
per 1 million population, accounts f or 0.2% in the
structure of cancer of the digestive tract and 16.4% in
the structure of cancer of the bile ducts.
Due to the anatomical features of the ampulla of
Vater, the course of the disease and the development of
the clinical picture, ampu llary cance r is usually
diagnosed at an early stage. Therefore, in more than
half of the observa tions of primary treatment, it is
possible to carry out a radical treatment regimen.
PDR is a standard surgery for ampullary cancer.
The data of the morphologic al study of our own
clinical material show that the choice of the extent of
the surgical aid (th e depth of dissection) directly
depends on the histological type of ampullary cancer.
In the intestinal type and resectable tumor process, the
standard PDR is a radical vo lume; three (7.1%) of 42
cases of intestinal type had metastases to juxta -regional
lymph nodes detected. In the pancreatic -biliary type,
various combinations of morphological signs (tumor
growth in the MPVS, metastatic lesions of juxta -
regional lymph nodes , perineural invasion, the presence
of tumor emboli) amounted to 27 (39.7%) of 68 cas es.
Thus, the radical volume of the operation in the
pancreatic -biliary type must be recognized as the
extended GPDR.
Since half of all ampullary cancers recur after
radic al primary intervention, it is of paramount
importance to identify and manage (approp riately) the
features associated with the risk of disease recurrence.
Currently, a group of unfavorable morphological signs
has been identified and constantly r evised, the se are
growth into surrounding organs and tissues, perineural
invasion, metastatic le sions of lymph nodes, low tumor
differentiation, etc., which determine an early relapse
of the disease and a low life expectancy. The
overwhelming majority of t hese progno stically
unfavorable morphological signs are inherent in the
pancreatic -biliary type of ampullary cancer, i.e.
histological type of ampullary cancer is an independent
predictor of long -term survival; the overall 5 -year
survival rate for pancreat ic-biliary and intestinal types
is 27.5 -53.3% and 61 -73%, respectively. In our study,
we compare d long -term survival in the groups of
pancreatic -biliary and intestinal types, where the
radical treatment regimen included extended GPDR
without neoadjuvant th erapy. The overall 5 -year
survival rate and average life expectancy in the studied
groups, respe ctively, were 9.8% versus 61.3% (p
<0.001) and 21.7 ± 6.11 months against 60.5 ± 9.15
months (p = 0.0007).
The high relapse rate is a strong argument for
consid ering multi modal treatment for ampullary
cancer.
Currently, the data on the effectiveness of the use
of adjuvant therapy in the radical treatment regimen for
ampullary cancer are contradictory.
ESPAC -1 (1997) of cases with R0 resection
revealed the median survival i n groups with and
without adjuvant chemotherapy equal to 15.9 months
against 16.9 mon ths, respectively. According to the
results of EORTC -40891 (1999), the 2 -year survival
rate for ampullary cancer in the control group and the
group of adjuvant chemotherap y was 63% and 67%,
respectively (p = 0.737). ESPAC -3 (v2, 2016), for
ampullary cancer , revealed the median survival in the
control group and the combination treatment group,
respectively, equal to 34 months and 57 months,
respectively. According to B.L. Ec ker et al. (2019)
regardless of the stage of the tumor process, the
severity, the pre sence/absence of tumor cells at the edge
of the resection, the presence/absence of metastatic
lesions of the lymph nodes, histological type, adjuvant
therapy do es not play any role in improving overall
survival in patients with FS cancer. According to M.
Al-Jumayli et al. (2019) adjuvant therapy did not
change relapse -free and overall survival rates. The 5 -
year survival rate was 22.7%.

34 American Scientific Journal № ( 41) / 2020
Analysis of a large sample of NCDB sho wed the
following. Group with adjuvant chemotherapy and
without adjuvant chemotherapy: median overall
survival was 47.2 and 35.5 months, 1 -year survival -
90% and 85%, 3 -year - 57% and 49%, 5 -year - 44% and
38%, respec tively. It was stated that adjuvant
chemotherapy significantly increased life expectancy
in the group with the T3/T4 index. Group with adjuvant
chemotherapy and without adjuvant chemotherapy:
median overall survival was 38.1 months, respectively.
versus 31 .0 months, 1 -year survival rate - 88% versus
83%, 3 -year survival rate - 51% versus 45%, 5 -year
survival rate - 40% versus 35%. Adjuvant CRT
significantly increased life expectancy in the group
with metastatic lymph node involvement. A recent
series from t he Mayo Clinic (2018) demon strated the
benefit of adjuvant chemotherapy in stage IIB or
higher. According to the data obtained, a 55% reduction
in the risk of death was noted in patients with advanced
disease receiving adjuvant therapy [HR: 0.45, (95% CI:
0.22 –0.93), P = 0.03]. Simi lar encoura ging results were
obtained in another retrospective series, which
collected data from the National Database, including
4190 patients with ampullary cancer. There was a 18%
reduction in the risk of death [HR: 0.82, (95% CI: 0.71 –
0.95)], which is typical for large tumors and advanced
stages. In our study, we used two modes of adjuvant
chemotherapy (based on the results of the ESPAC -3
study): Mayo and gemcitabine monotherapy. We do not
consider these chemotherapy regimens to be successful
for ampull ary cancer. Probably, in the future,
chemotherapy regimens for the pancreatic -biliary type
will be represented by various combinations of 5 -FU,
gemcitabine and capecitabine; for the intestinal type,
the FOLFOX regimen is possible .
Neoadjuvant treatment is represented by single
observations in the form of retrospective reports
(Yeung R.S. et al., 1993; Hoffman J.P. et al., 1998;
Palta M. et al., 2011). Randomized controlled trials are
absent. Nevertheless, the authors noted a high
frequency of grade 4 treatm ent pathomo rphosis (80 -
100%) in the removed specimens, partial (67%) and
complete (28%) tumor response. Considering the above
and agreeing with the opinion of C.G. Willett et al.
(1993) that preoperative RT will reduce the risk of
dissemination of cancer c ells during surgery, we
conducted a single -center retrospective prospective
study to evaluate the combined treatment of pancreatic -
biliary type of ampullary cancer. The overall 5 -year
survival rate and average life expectancy in th e groups
of combined trea tment (preo perative RT and extended
GPDR) and extended GPDR without preoperative RT,
respectively, were 50.7% versus 9.8% (p = 0.01) and
74.8 ± 12.58 months versus 21.7 ± 6.11 months (p =
0.0008). The relatively small number of obs ervations
with the discus sed nosolog y did not allow us to
compare the long -term survival rate taking into account
the stages of the tumor process.
The above studies of neoadjuvant treatment of
ampullary cancer pay little attention to the damage to
radiatio n therapy, methods of con trol and dr ug
correction of these pathological conditions. R.S. Yeung
et al. (1993) reported that the diagnosed toxicity was
represented by febrile neutropenia (in 2 cases), biliary
sepsis (in 2 cases), nausea and vomiting. One pat ient
died of biliary seps is prior to completion of CRT. J.P.
Hoffman et al. (1998) the problem of the safety of
neoadjuvant therapy was not discussed, probably due to
the small number of observations. M. Palta et al. (2012)
bypassed the topic of chemothera py toxicity, noting
only the disadva ntages - the preoperative time interval
during which the patient's condition may worsen, the
disease progresses, which excludes subsequent surgical
intervention. In our study, during remote radiotherapy,
radiation injuri es occurred in 28.6% of c ases: grade 1
erythema - in 19.1%, grade 1 leukopenia - in 4.75%,
and grade 2 leukopenia - in 4.75% of cases. The above -
mentioned injuries of radiation therapy were arrested
against the background of conservative therapy for a
shor t period of time, in part icular, ery thema within 4 -
10 days from the moment of completion of radiation
therapy, leukopenia - one day after completion of
radiation therapy, and did not increase the duration of
the preoperative period.
To finalize the discuss ion we should say that th ere
are no malignant neoplasms insensitive to radiation
therapy. Achievement of therapeutic effect requires
selecting correctly the type of ionization radiation, the
method and dose of energy supply to the focus, the
sequence for c ombined treatment. The sa me applies to
drug therapy, it is necessary to choose the right
chemotherapy regimen. As for the contradictory data
regarding the effectiveness of the above therapy, the
reason probably lies in the study protocol itself and its
com ponents, namely, the retr ospective n ature of the
study, a small number of observations in ongoing
studies (due to the rarity of the discussed nosology), the
heterogeneity of the compared groups by histological
type of ampullary cancer and disease neglect ( patients
who received adj uvant thera py after PDR have more
advanced disease), lack of proper control of
chemotherapy regimens, differences in the volume of
operations (mainly due to the depth of dissection), etc.
For correct conclusions, a multicenter rand omized
controlled trial i s required.
Intestinal and pancreatic -biliary types of
ampullary cancer are two different tumor processes
with different tumor biology, local manifestations, drug
sensitivity and disease prognosis. The pancreatic -
biliary type is mo rphologically,
immunohist ochemically and clinically similar to ductal
cancer of the pancreas and assumes the same type of
treatment regimen represented by neoadjuvant therapy
and appropriate chemotherapy regimens. The intestinal
type is morphologically and clinically similar to
colorectal ca ncer, showing tropism for similar drugs.
This is the second strong argument for starting a
multicenter randomized controlled trial to confirm
these claims.

American Scientific Journal № ( 41) / 2020 35

Abbreviations
GPDR - gastropancreaticoduodenal resection
RT - radiation therapy
MPV S - mesentrico -portal venous system
PDR - pancreaticoduodenal resection
P - pancreas
rLa - right liver artery
AV - ampulla of Vater
CT - chemotherapy
CRT - chemoradiotherapy

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УДК 13058
ГРНТИ 76.29

ГЕМОПЕРФУЗИЯ ПРИ ОСТРОМ ОТРАВЛЕНИИ ПСИХОТРОНЫМИ ПРЕПАРАТАМИ

Фомин Александр Михайлович
Ведущий научный сотрудник
ГБУЗ МО «МОНИКИ им. М.Ф.Владимирс кого»,
Москва, Россия.

HEMOPERFUSION IN ACUTE PSYCHOTROPIC POISONING

Fomin Aleksander Mikhailovich
Moscow Regional Re search and
Clinical Institute (MONIKI), Moscow, Russia.
DOI: 10.31618/asj.2707 -9864.20 20.3.41.35
Аннотация . Представлено комплексное лечение пациентки с острым отравлением ам итриптилином
и циклодолом с применением энтеросорбции, кишечного л аважа и гемосорбции на новой кол онке с
синтетическим сорбентом. Для гемосорбции использована колонка с двухслойным синтетическим
полимером, разработанная для селективной сорбции цитокинов ме тодом прямой гемоперфузии.
Количеств енные определения уровней амитриптилина и циклодола до колонки и после колонки, а также
до гемосорбции и после гемосорбции показали высокую эффективность сорбента по удалению токсикант а
из крови. Применение 6 часовой гем осорбции позволило снизить уровень а митриптилина от исходного
более чем в 4 раза и уровень циклодо ла - более чем в 3 раза до терапевтических уровней и получить
выраженный положи тельный клинический эффект в комплексном лечении пациентки с тяжелым
отравление м.
Summary. Presented is a complex treatment of a patient with acute amitriptyline and cyclodole p oisoning
using enterosorption, intestinal lavage and hemosorp tion on a new column with a synthetic sorbent. For
hemosorption, a column with a two -layer synthe tic polymer was used, developed for selective sorption of
cytokines by direct hemoperfusion. Quant itative measurements of levels of amitriptyline and cyclodole before and
after the column, as well as before haemosorption and after haemosorption, showed a h igh effectiveness of the
sorbent in removing toxicant from the blood. The use of 6 -hour hemosorpti on allowed to reduce the level of
amitriptyline from the init ial by more than 4 times and the level of cyclodole by more than 3 times to therapeutic
levels an d obtain a pronounced positive clinical effect in the complex treatment of a patient with severe p oisoning.
Ключевые слова : острое отравление, амитриптилин, ц иклодол, гемосорбция.