Although laparoscopy-assisted gastrectomy for gastric cancer has been applied in the world since 1991, it was not until 2007 that this technique was used widely at large medical centers in Vietnam. However, there have been no studies to evaluate the long-term survival of method so far. Subjects and methods: To study 165 gastric cancer patients undergoing laparoscopy-assisted gastrectomy with D2 lymph node dissection at 103 Military Hospital from April 2009 to August 2013. Surgical procedures according to instructions of Ministry of Health. Lymph node dissection and postoperative stage according to 3rd JGCA were diagnosed. Patients were followed at least 5 years after surgery, intra-and-postoperative complications, recurrence and metastases were recorded and managed.
Trang 1LONG-TERM SURVIVAL OUTCOMES OF LAPAROSCOPY-
ASSISTED GASTRECTOMY WITH D2 LYMPH NODE
DISSECTION FOR GASTRIC CANCER AT 103 MILITARY HOSPITAL
Ho Chi Thanh 1 ; Hoang Manh An 1 ; Dang Viet Dung 1 ; Nguyen Van Xuyen 1
Nguyen Trong Hoe 1 ; Le Thanh Son 1 ; Phan Hung Phuc 2 ; Nguyen Van Tiep 1
SUMMARY
Background: Although laparoscopy-assisted gastrectomy for gastric cancer has been applied
in the world since 1991, it was not until 2007 that this technique was used widely at large
medical centers in Vietnam However, there have been no studies to evaluate the long-term
survival of method so far Subjects and methods: To study 165 gastric cancer patients
undergoing laparoscopy-assisted gastrectomy with D2 lymph node dissection at 103 Military
Hospital from April 2009 to August 2013 Surgical procedures according to instructions of
Ministry of Health Lymph node dissection and postoperative stage according to 3 rd JGCA were
diagnosed Patients were followed at least 5 years after surgery, intra-and-postoperative
complications, recurrence and metastases were recorded and managed Analysis and
processing of data were performed by using SPSS software version 15.0 Results: Mean
operative time was 205.7 ± 51.8 minutes, mean number of lymph nodes dissection per one
patient was 21.5 ± 6.09 The incident in surgery was 1.81%, complications after surgery was
4.2%, postoperative mortality rate was 0.6%, cancer recurrence and metastasis was 44.8%
Survival outcomes of postoperative five-year follow-up were 50.3%; with 93.3% in the stage Ia,
89.7% in the stage Ib; 61.7% in the stage IIa; 70.0% in the stage IIb; 25% in the stage IIIa; 7.7% in the stage IIIb and 0% in the stage IIIc Conclusions: Our study found that the long-term
outcome of laparoscopy-assisted gastrectomy with D2 lymph node dissection for gastric cancer
was promising and acceptable Survival outcomes after surgery depends on the stage and
lymph node metastasis status
* Keywords: Gastric cancer; Laparoscopy-assisted gastrectomy; D2 lymph node dissection;
Long-term survival outcomes
INTRODUCTION
Gastric cancer is the most malignant
disease in gastrointestinal cancer,
according to Global Cancer Statistics
in 2018, with mortality rate of 8.2%, which
comes the second, just after lung cancer, common in both men and women [1]
Radical gastrectomy with lymphadenectomy
is the most effective treatment, increasing the survival rate
1 103 Military Hospital
2 Vietnam Military Medical University
Corresponding author: Ho Chi Thanh (hochithanh103@gmail.com)
Date received: 20/11/2018
Date accepted: 14/01/2019
Trang 2Laparoscopic gastrectomy for early gastric
cancer was first performed by Kitano in
1991, so far many surgeons in the world
have done this technique For advanced
gastric cancer, gastrectomy with D2 lymph
node dissection is considered standard
surgery, however, with laparoscopy assisted,
surgeons suspect the radicalization of the
method [2, 3] In Vietnam,
laparoscopy-assisted gastrectomy (LAG) with D2
lymph node dissection for gastric cancer
has been performed in big hospitals, but
short follow-up time and there have been
no studies of evaluating the long-term
survival outcome Therefore, we studied
this study: To evaluate long-term survival
outcome of LAG with D2 lymph node
dissection for gastric cancer
SUBJECTS AND METHODS
1 Research subjects
165 patients were diagnosed with gastric
adenocarcinoma, who was LAG with D2
lymphadenectomy from April 2009 to
October 2013, at Abdominal Surgery
Department, 103 Military Hospital
- The procedure of LAG was uniform
under the treatment guidelines of Ministry
of Health issued in 2013 for laparoscopic
gastrectomy with D2 lymphadenectomy [4]
- The patients were the first people to
undergo laparoscopic gastrectomy, afterwards,
they conversed to open surgery
2 Methods
- Descriptive study, tracking down
uncontrolled
- Patient was followed up after surgery with 3rd JGCA, follow-up time at least
60 months All cases of recurrence, metastases and causes of death were recorded and confirmed [5]
* Handling of the resected specimen and description of histological findings:
- The specimens are opened along the greater curvature, cleaned, fixed and examination of macroscopic type, location, size, invasion of tumor Measurement
of tumor size along the margin of mucosal lesion, and the length of the proximal and distal resection margins were measured
- After dissection of lymph nodes from the specimen, station to number according
to 3rd JGCA, examples of macroscopic type, number of lymph nodes, and fixed
in 15 - 20% formalin solution, sent to histopathology department
- The results of postoperation stage according to 3rd JGCA [5]
* Statistical analysis:
- Data were processed by the Kaplan-Meier method using SPSS software, version 15.0
RESULTS
1 Characteristics of patients
- Mean age: 56.1 ± 11.38 (range,
26 - 81 years)
- Male: 113 patients (68.5%); female:
52 patients (31.5%)
Trang 32 Pathological characteristics
Table 2:
Tumor location
Macroscopic type
T stage
Histological type
Poorly
differentiated
Lymph node stage
TNM stage
3 Surgical outcomes
Mean operative time: 205.7 ± 51.8 mins
Average lymph node dissection:
21.5 ± 6.09
Table 3:
Type of gastrectomy
Complications
Mortality (because of
* Recurrence and metastasis (n = 74; 44.8%):
Peritoneum: 50 patients (30.3%); liver:
7 patients (4.2 %); hepatic lymph node:
6 patients (3.6%); colon: 3 patients (1.8%);
lung: 2 patients (1.2%); brain: 1 patient
(0.6%); rectum: 1 patient (0.6%); troiser:
2 patients (1.2%); ovary: 1 patient (0.6%); spine: 1 patient (0.6%)
Trang 4Table 4: Results of follow-up survival
Figure 1: Follow-up overall survival
Overall 5-year survival rate was 50.3%
Figure 2: Follow-up overall survival of sex
Overall 5-year survival rates of male
and female were 54.9% and 50.0%, test
Log Rank χ2 =0.389, p = 0.533
Figure 3: Follow-up overall survival
of macroscopy
Overall 5-year survival rates of polypoid, ulcerated, infiltrative ulcerated and infiltrative were 68.8%, 74.7%, 25.4% and 28.6%, test Log Rank χ2 =49.220, p = 0.000
Figure 4: Follow up overall survival
of T stage
Overall 5-year survival rates of T1, T2, T3 and T4a were 90.5%, 70.1%, 33.3% and 7.1%, test Log Rank; χ2 =56.538, p = 0.000
Figure 5: Overall survival rates of lymph
node stage
Overall 5-year survival rates of pN0, pN1, pN2 and pN3 were 86.4%, 72.4%, 38.9%
Trang 5and 4.9%, test Log Rank χ2 = 148.978,
p = 0.000
Figure 6: Overall survival rates of TNM stage
Overall 5-year survival rates of Ia, Ib, IIa,
IIb, IIIa, IIIb and IIIc were 93.3%, 89.7%,
61.53%, 70.0%, 25.0%, 7.7% and 0.00%,
test Log Rank χ2
=148.978, p = 0.000
Figure 7: Overall survival rates of
histological
Overall 5-year survival rates of papillary,
tubular, mucinous, signet-ring cell and poorly
differentiated carcinoma were 87.5%, 63.2%,
53.8%, 47.1% and 38.9%, test Log Rank
χ2 =28.073, p = 0.000
Figure 8: Overall survival rates of
type gastrectomy
Overall 5-year survival rates of distal, subtotal, total and proximal gastrectomy were 54.3%, 36.4%, 44.4% and 80%, test Log Rank χ2 = 5.152, p = 0.161
DISCUSSION
1 Patients’ characteristics
The mean age was 56.1 ± 11.38 years, males occupied 68.5% and females
accounted for 31.5% (table 1) These results
were consistent with domestic and foreign studies, according to Global Cancer Statistics report in 2018, rates were 2-fold higher in men than in women [1, 6, 7]
Tumor location with lower third was 86.7%, middle third was 9.09% and upper
third was 4.24% (table 2) Pathological
classifications were the most of ulcerated carcinomas (47.9%) and infiltrative ulcerated carcinomas were 38.2%, polypoid tumors was 9.7% and diffuse infiltrative carcinoma was 4.24% Depth of tumor invasion with T1, T2, T3 and T4a were 12.7%; 40.6%,
with the characteristics of gastric cancer
in domestic studies: mostly in the lower third, macroscopic type was usually ulcerated and was advanced stages, surgery and prognosis was poor Park et al: T2, T3 and T4 were 25.7%; 58.7% and 15.6%; tumor location with upper, middle and lower third were 16.1%; 11.3% and 69.0%, respectively [6] Kim et al reported: tumor location with upper, middle and lower third were 5.8%; 23.8% and 70.0%; T1a, T1b, T2, T3 and T4 were 47.1%; 30.4%; 10.4%, 6.6% and 4.4%, respectively [7] Histological characteristics: Papillary, tubular, mucinous adenocarcinomas were
Trang 614.5%; 23.0% and 7.87% Signet-ring cell
and poorly differentiated adenocarcinoma
were 10.3% and 43.6% One case of
squamous cell carcinoma was 0.6%
According to Kitano et al, tubular,
signet-ring cell adenocarcinoma and others were
78.7%, 19.7% and 2.4%, respectively [2]
Kim et al reported, signet-ring cell was 7.8%
and poorly differentiated adenocarcinoma
was 33.9% [7]
Characteristics of lympho node
metastasis: pN0, pN1, pN2 and pN3
were 35.7%, 17.6%, 21.8% and 24.8%
Park et al [6]: pN0, pN1, pN2, pN3 were
44.0%, 16.5%, 13.5% and 25.7% Fang
et al: pN0 was 43.7%, pN1 was 24.1%,
pN2 was 19.5% and pN3 was 12.6% [8]
Pathological stages according to 3rd
JGCA: Ia and Ib were 9.09% and 23.6%;
IIa and IIb were 21.8% and 12.1%; IIIa,
IIIb and IIIc were 16.9%, 15.8% and 6.67%
(table 2) This result was also consistent
with our domestic research, the early
gastric cancer was diagnosed in Vietnam
is much lower than that in Japan and
Korea Kitano et al showed that the rate of
stage disease for Ia, Ib and II were
93.7%, 5.8% and 0.5%, respectively [2]
Kim et al indicated the rate of stage I, II
and III were 82.2%, 11.7% and 5.0% [7]
Huscher C et al, the rate of stage Ia was
20.7%; Ib was 20.7%; II was 13.8%, IIIa
was 17.2%; IIIb was 10.4% and IV was
17.2% [3]
2 Operative results
Mean operative time was 205.7 ± 51.8
minutes, average number of dessected
lymph nodes was 21.5 (table 3), which could
be acceptable compared with open surgery and other authors’ findings [2] The operative time in Huscher et al’s study was 196 ±
21 minutes, mean number of lymph nodes dissected was 30.0, which were 322.9 ± 116.6 minutes and 28.5 lymh nodes in Park et al’s stduy; 214.0 ± 52.6 minutes and 34.7 lymph nodes in Kim et al’s;
337 minutes and 32 lymph nodes in Fang
et al’s; 240 ± 58.2 minutes and 35 lymph nodes in Honda et al’s [3, 6, 7, 8, 9] There were 5 laparoscopy-assisted proximal gastrectomy (LAPG), 140 laparoscopy-assisted distal gastrectomy (LADG),
11 laparoscopy-assisted subtotal gastrectomy (LASG) and 9 laparoscopy-assisted total gastrectomy (LATG) This result was consistent with Kitano et al’s: LADG was 91.5%, LAPG was 4.2% and LATG was 4.3% [2], Kim et al reported LADG was 90.5%, LAPG was 0.3% and LATG was 9.2% [7]
The incidence in surgery was 5 cases (3.03%), of which two patients suffered from bleeding by injury splenic artery during dissected 11p, to clip splenic artery
to stop bleeding were not performed splenectomy There was one case of spleen injury This patient had to do laparoscopic spelenectomy Two cases of injured transverse colon, we had to make colostomy Kitano et al, complications of intraoperative was 1.7% in LADG group, 7.4% in LAPG group and 1.8% LATG group [2]
Postoperative complications: 8 cases (4.8%), in which there were two cases with duodenal stump leak (1.2%), resurgery
Trang 7to drainage duodenum, after that the patient
was rather well and discharged from hospital
There was one patient with anastomotic
leak on 5th postoperative day (0.6%), who
was performed subtotal gastrectomy with
anemia anastomosis This patient had to
undergo reoperation for total gastrectomy
and was connected jejunum to oesophagus
As a result, the patient recovered a little
and discharged from hospital In the case
of patient undergoing subtotal gastrectomy
with lymphadenectomy and resection all
of short gastric vessels, total gastrectomy
should be performed and jejunum has to
be connected to the oesophagus so that
it is better nourished Residual abscess
was found in two cases on 4th and 5th
post-operative day (1.2%), treated
conservatively, drained fluid under
ultrasound, patients were stable and
discharged after 5 days Incision infection
was observed in one case (0.6%), the
patients were taken care and closed
second incision and patient was fine and
discharged Compared to open surgery
and other authors’s findings, our postoperative
complications were acceptable Kitano et
al reported complication was 14.8% [2]
In Huscher’s study, this rate was 23.3%,
including acute pancreatitis, pleural effusion,
bleeding and wound infection and
conservative treatment, without reoperation
[3] Kim et al conducted a study on
753 patients of LG, rate of complication
was 10.2%, including six cases of duodenal
stump leakage, anastomotic leak were 3
cases, bleeding was encountered in one
case and residual abscess was in one
case [7]
Respiratory failure and death after surgery: 1 case (0.6%) The patient was
74 years old, stage IIIb, pyloric stenosis, respiratory failure on day 6th after surgery Kim et al reported mortality after surgery was 0.1%; in Huscher et al’s study, there was one case of mortality after surgery due to respiratory failure (3.3%) [3, 7]
* Recurrence and metastasis:
Recurrence and metastasis after gastrectomy for gastric caner were common causes of mortality and decreasing survival In table 4, recurrence and metastasis occurred in 74 patients (44.8%),
in which recurrent peritoneal was the highest rate of 30.3%, metastatic liver was 4.2%, liver metastatic lymph node to obstruction of the bide duct were 6 cases (3.36%), metastatic colon: 3 cases (1.8%), lung metastasis: 2 cases (1.2%), metastatic troiser: 2 cases (1.2%), metastatic brain: one case, metastatic Krukenber: one case, metastatic rectum: one case and metastatic spine: one case Of the 74 recurrences, there were 5 cases of reoperation,
71 case were dead and 3 cases were alive with 2 cases of metastatic liver and one case of metastatic colon There were
no port-site and no incision metastases were observed Park et al: recurrence was 50.7% in the open surgery group and 29.4% in the laparoscopic group, there was no differences between two groups
In the recurrence group, metastatic peritonea was the highest (18.7%), metastatic an intra-abdominal organ was 17.3% and metastases liver was 16.0% [6] Honda
et al, 5 years after surgery found that peritoneal metastases was 0.76% and
Trang 8metastases liver was 0.87% [9] Chen
et al, the mean follow-up was 39.7 months
and found that 40 patients developed
tumor recurrence, in which peritoneal
recurrence was the highest (45.0%),
27.5% of distant recurrence, 17.5% of
lymphatic recurrence and 10.0% of
locoregional recurrence [10]
4 Follow-up survival results
Follow-up survival of after cancer
surgery was very interesting, in table 5
and figure 1, the shortest was 60 months,
the longest was 111 months, the average
survival rate were 53.9 ± 31.3 months
5 cases were lost to follow-up assessment,
giving a follow-up rate of 96.96% The
5-year overall survival and disease-free
survival was 80 cases (50.3%) and 77 cases
(48.4%) Death was found in 77 cases
(46.7%) and 71 cases of death (43.0%)
was due to recurrence and metastasis,
6 cases of death due to other causes
These results were consistent with
Huscher et al’s study, followed up with 30
patients of LG, an average survival were
52.2 ± 26.5 months, a survival rate of
58.9% for 5 years, recurrence rates were
37.9% and all died from recurrent disease
[3] Kim et al, the average follow-up time
were 56.2 months, after 5 years’ surgery,
overall survival rate was 97.1% and
disease-free survival rate was 96.3%,
the recurrence rate was 3.3% [7]
Analysis of factors related to
post-operation, we used Log Rank test In figure
2, 5-year survival rate in male was 54.9%
and 50.0% in female, but the Log Rank
χ2
= 0.389, p = 0.533, so the gender was
not related to overall survival after surgery
Follow-up survival of the macroscopic tip at figure 3, we found that the 5 year overall survival of mass was 68.8% and that of ulcerative was 74.7%, higher than the infiltrative ulcerative and diffused infiltrative was 25.4% and 28.6%, significantly different with the Log Rank test χ2 = 49.22 and p = 0.000 The relative between invasive stages and survival after surgery, figure 4 shows that 5-year survival rate of invasive stage T1, T2, T3 and T4a was 90.5%, 70.1%; 33.3% and 7.1%, significant difference with the Log Rank test χ2 = 56.538 and p = 0.000 Fang et al, 5 year overall survival of LADG group was 59%, Chen et al, the 5-years overall survival in T1, T2, T3 and T4a was 92.1%, 84.6%, 65.9%, and 40.7%, respectively [8, 10]
Follow-up survival of the lymph node stages at figure 5 The 5-year survival rate of the cases with non-lympho node metastasis (pN0) was 86.4%; the pN1 was 72.4%, the pN2 was 38.9% and pN3 was 4.9%, significant difference with Log Rank test χ2 = 148.978 and p = 0.000 In figure 6, the 5-year overall survival rate of stage Ia, Ib, IIa, IIb, IIIa, IIIb and IIIc was 93.3%; 89.7%, 61.53%, 70.0%, 25%, 7.7% and 0%, significantly different, with test Log Rank χ2 = 56.538 and p = 0.000 Our results were consistent with Kim et al’s: 5 year overall survival of stage I, II and III was 99.5%, 89.5% and 76.1% [7]
Trang 9Kitano et al reported the 5-year
disease-free survival rate was 99.8% for stage Ia,
98.7% for stage Ib and 85.7% for stage II
[2] Park et al reported in LG group, 5-year
overall survival rate of stage I, II and III
was 87.5%, 77.3% and 34.8% [6] Honda
studied LG for gastric cancer of stage I,
the 5-year overall survival rate was 97.1%
[9] Chen et al, according to tumor stage,
5-year overall survival was 93.1% for
stage I, 67.6% for stage II and 41.5% for
stage III [10]
Follow-up survival of histopathology at
figure 7, the 5-year overall survival of
papillary, tubular, mucinous, signet-ring cell
and poorly differentiated adenocarcinoma
was 87.5%, 63.2%, 53.8%, 47.1% and 38.9%,
respectively One patient with squamous
cell carcinoma died after 11 months,
significant difference with test Log Rank
χ2 = 28.073 and p = 0.000 According
to Japanese authors, the intestinal type
has a better prognosis; diffused type,
adenosquamous and squamous cell
carcinoma have less prognosis than other
cells, the survival rate of 5 years is less
than 10% [5]
In figure 8, the 5-year survival rate of
distant gastrectomy group was 54.3%, the
rate of proximal gastrectomy was 80.0%,
the rate of total and subtotal group was
44.4% and 36.4% The difference was
not significant with Log Rank χ2 = 5.152
and p = 0.161 Although there was no
difference, with total and subtotal gastrectomy,
their tumor were not detected early, size
of tumor were big, wide invasion so surgery
and postoperative prognosis will be not good
CONCLUSIONS
The study on 165 patients with gastric cancer were LAG with D2 lymph nodes dissection, we found that it was technically feasible, safe and a good long-term outcome The median survival was 53.9 ± 31.3 months, the 5-year overall survival was 50.3% The survival time was dependent on TNM stage, T-stage, lymph node metastatis stage, type of macroscopic and histological type with p < 0.01 Survival time was not dependent on gender and type of gastrectomy with
p > 0.05 However, the limitation of the study was small and compared with open surgery, therefore, we really need a large-scale multicenter randomized trial to confirm the oncological safety and feasibility
of LAG for patients with advanced gastric cancer
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