Oliynyk and Slipetsky: Features of Histological Forms of Tumor Growth in Patients Who Underwent Combined Surgery for Stomach Cancer



Problem statement and analysis of the recent research

Despite advances in early cancer detection, stomach cancer (SC) remains the leading cause of cancer death after lung cancer worldwide [4]. It is mainly due to the fact that a significant proportion of locally advanced forms of SC is diagnosed too late, especially in Ukraine (over 20-25%) [1].

Surgery which involves achieving a R0 resection, is often used in patients with locally advanced forms (T4) of SC [8]. Over recent years, the increase in the rate of complications in the postoperative period as well as survival rate has been actively discussed. Some researchers have reported minor changes in the survival of patients who underwent combined surgery [6]. However, significantly higher rates of complications and mortality as well as a slightly longer duration of in-patient treatment due to extended resections have been indicated by other authors [6].

The microscopic type of tumor is a crucial factor in selecting the type and volume of surgery [7]. In addition, other clinical and pathological characteristics of tumor such as the depth of invasion, lymph node status, macroscopic type, tumor size and others affect the prognosis of locally advanced SC.

The objective of the research was to study the effect of histological type of tumor on survival and prognosis of patients with locally advanced SC after combined surgery.

Materials and methods

The study included 990 patients; there were 714 men and 276 women. All patients underwent various types of combined surgery for SC in Lviv Regional Clinical Oncology Center. Surgery was considered “combined” when the main type of surgery (subtotal gastric resection or gastrectomy) was combined with en bloc resection or removal of other (related) organs (the mesentery of the transverse colon, the transverse colon, the body and tail of the pancreas, spleen, diaphragm, soft tissue of the anterior abdominal wall). Distal subtotal gastric resection (n=222), proximal subtotal gastric resection (n=129) or gastrectomy (n=639) were performed depending on the location of the primary lesion and other JGCA criteria [5]. The additional organ resection was performed to achieve R0 resection; in some cases, due to iatrogenic damage to the organ. All the data were statistically processed using the SPSS 13.0 software program (Chicago, IL). The obtained numerical indicators were presented as M±m, and the difference between groups was compared using the independent bilateral T-test. To compare frequency parameters between groups, the χ2-square test (Fisher’s exact test) was used. The time interval between the time of surgery and the date of death or last contact (if alive) was used to analyze survival data by means of the Kaplan-Meier method and the log-rank test. In all cases, the results were considered statistically significant at p<0.05

Results and

The average age of patients was 60.02±0.30 years (generally from 21 up to 87 years); male patients prevailed over female patients– men:women = 2.6:1.0 (72.1%: 27.9%). Among all combined surgical procedures, combined gastrectomy predominated over combined subtotal gastric resection and proximal gastric resection - 5:2.9:1.

Table 1

Average life expectancy of patients with stomach cancer depending on histological forms of tumor growth and gender

# Histological forms (WHO) Average life expectancy (months) Median of average life expectancy (months) 5-year survival rate (%)
M ±m 95% confidence interval M ±m M ±m
Lower limit Upper limit
All patients
1 Adenocarcinoma 41.21 3.29 34.76 47.66 12.85 0.88 19.33 1.83
2 Small-cell cancer 29.34 28.97 0.00 86.13 0.39 0.05 33.33 27.22
3 Undifferentiated cancer 25.29 3.28 18.87 31.73 9.73 1.26 12.04 2.55
4 Squamous cell cancer 10.79 4.73 1.51 20.07 5.29 1.74 - -
Total 37.51 2.69 32.24 42.78 12.03 0.69 17.32 1.49
Men
5 Adenocarcinoma 37.99 3.59 30.95 45.04 12.03 0.84 17.52 2.05
6 Small-cell cancer 0.36 0.03 0.29 0.43 0.33 - - -
7 Undifferentiated cancer 24.74 4.03 16.85 32.62 8.45 0.98 12.53 3.27
8 Squamous cell cancer 6.57 2.48 1.72 11.42 5.29 2.37 - -
Total 35.13 3.02 29.21 41.05 11.28 0.77 16.113 1.72
Women
9 Adenocarcinoma 50.45 7.48 35.786 65.11 14.69 1.76 24.69 3.96
10 Small-cell cancer 87.29 0.00 87.29 87.29 87.29 - 1.00 0.01
11 Undifferentiated cancer 26.33 5.46 15.62 37.04 12.13 1.66 11.47 4.06
12 Squamous cell cancer 40.34 0.00 40.34 40.34 40.34 - - -
Total 43.75 5.70 32.58 54.93 14.17 1.43 20.46 2.99

The average life expectancy of 701 (512 men, 189 women) patients after surgery was 37.51±2.69 months (p=0.021); in women, it was slightly higher compared to men – 43.75±5.70 months vs. 35.13±3.02 months (p=0.057). The median survival time was 12.03±0.59 months, 20.46±2.99 months and 16.11±1.72 months, respectively (Table 1). The highest average life expectancy was in patients with adenocarcinoma – 41.21±3.29 months; the lowest average life expectancy was in patients with squamous cell cancer – 10.79±4.73 months (p=0.041); significantly lower average life expectancy was observed in patients with undifferentiated cancer – 25.29±3.28 months (p=0.015). The study of certain morphological types of tumors depending on the patients’ age and sex, as well as clinical and morphological features revealed a significant predominance of adenocarcinoma (77.1%) over other types and a significantly smaller number of undifferentiated tumors – 20.6%; squamous cell cancer and small-cell cancer constituted 1.3% and 1.0%, respectively (Table 2).

Table 2

Clinical and morphological data of patients with different histological types of stomach cancer

Adenocarcinoma1 (n=763) Small-cell cancer2 (n=10) Undifferentiated cancer3 (n=204) Squamous cell cancer4 (n=13) p-value
Age, years 60.58±0.34 55.20±2.12 58.84±0.92 59.00±3.01 p1-2=0.793
p1-3=0.363
p1-4=0.653
Sex
Women 197 (25.8%) 4 (40.0%) 74 (36.3%) 1 (7.7%) p1-2>0.05
p1-3<0.01
p1-4>0.05
Men 566 (74.2%) 6 (60.0%) 130 (63.7%) 12 (92.3%) p1-2>0.05
p1-3<0.01
p1-4>0.05
Macroscopic type
Exophytic 272 (35.6%) 2 (20.0%) 28 (13.7%) 5 (38.5%) p1-2>0.05
p1-3<0.01
p1-4>0.05
Endophytic 224 (29.4%) 8 (80.0%) 90 (44.1%) 3 (23.1%) p1-2 <0.05
p1-3<0.01
p1-4>0.05
Mesophytic 132 (17.3%) - 32 (15.7%) 3 (23.1%) p1-3>0.05
p1-4>0.05
Cancer originating from gastric ulcer 9 (1.2%) - 1 (0.5%) - -
Tumor localization
Proximal 381 (49.9%) 3 (30.0%) 73 (35.8%) 12 (92.3%) p1-2>0.05
p1-3<0.01
p1-4<0.01
Body 147 (19.3%) 1 (10.0%) 69 (33.8%) 1 (7.7%) p1-2>0.05
p1-3<0.01
p1-4>0.05
Distal 185 (24.2%) 4 (40.0%) 33 (16.2%) - p1-2>0.05
p1-3<0.05
Subtotal and total involvement 47 (6.2%) 2 (20.05) 28 (13.7%) - p1-2>0.05
p1-3<0.01
Multiple involvement 3 (0.3%) - 1 (0.5%) -
Depth of invasion
T1 10 (1.3%) -
T2 35 (4.6%) - 14 (6.9%) 1 (7.7%) p1-3>0.05
p1-4>0.05
T3 292 (38.3%) 1 (10.0%) 90 (44.1%) 7 (53.8%) p1-2>0.05
p1-3>0.05
p1-4>0.05
T4 415 (54.4%) 9 (90.0%) 100 (49.0%) 5 (38.5%) p1-2>0.05
p1-3>0.05
p1-4>0.05
Regional lymph nodes
N0 314 (41.2%) 5 (50.0%) 67 (32.8%) 3 (23.1%) p1-2>0.05
p1-3<0.05
p1-4>0.05
N1 301 (39.4%) 2 (20.0%) 92 (45.1%) 7 (53.8%) p1-2>0.05
p1-3<0.05
p1-4>0.05
N2 97 (10.1%) 2 (20.0%) 36 (17.6%) 3 (23.1%) p1-2>0.05
p1-3>0.05
p1-4>0.05
N3 3 (0.4%) - 3 (1.5%) -
Type of surgery
Gastrectomy 463 (60.7%) 6 (60.0%) 161 (78.9%) 9 (69.2%) p1-2>0.05
p1-3 <0.01
p1-4>0.05
Distal subtotal gastric resection 185 (24.2%) 4 (40.0%) 33 (16.2%) - p1-2>0.05
p1-3 <0.05
Proximal subtotal gastric resection 115 (15.1%) - 10 (4.9%) 4 (30.8%) p1-3 < 0.01
p1-4>0.05

Discussion

There were some differences in the average life expectancy by neoplasm morphology; the highest average life expectancy was observed in patients with adenocarcinoma of the stomach – 41.213±3.291 months, and the lowest one was observed in patients with squamous cell cancer – 10.793±4.734 months. There were detected significant differences in life expectancy between these groups of patients (p=0.041) and patients with adenocarcinoma as well as undifferentiated cancer (25.298±3.281 months) – p=0.015. There were no significant sex differences within the same type of morphology (p>0.05) [3]. The differences between life expectancy of patients with adenocarcinoma and small-cell cancer (29.34±28.97 months) were insignificant– p=0.491. In both male and female patients, the same patterns were mostly observed; it was apparently due to small number of observations – the differences were not determined between patients with small-cell cancer and squamous cell cancer; however, there was a significant difference between patients with adenocarcinoma and undifferentiated cancer (p=0.011). It should be noted that within each individual morphological form, there were observed minor gender differences; however, all of them were not statistically significant (p>0.05) [6, 8, 9]. There were determined no statistically significant differences in the average age of patients with different morphological types (p>0.1) [2]. Despite the overwhelming number of male patients (p<0.01), the most significant differences in adenocarcinomas and undifferentiated cancer were identified in both men and women (p<0.01) (Table 2), in rest cases there were not significant differences between the proportions of men and women (p>0.05) [6]. The most marked differences in the relative number of exophytic and endophytic tumors were found between adenocarcinoma and undifferentiated cancer (p<0.01) as well as endophytic tumors – between adenocarcinoma and small-cell cancer (p<0.05). There was no significant difference in the number of exophytic and endophytic tumors between the macroscopic forms of adenocarcinoma (p>0.1); however, the number of mesophytic tumors was significantly smaller compared to the previous one (p<0.01). Such value was not typical for other morphological types of tumors; however, undifferentiated tumors had significantly more endophytic forms (p<0.01) [8]. The predominant depth of invasion was T4 (p<0.01).

The status of affected lymph nodes in patients with adenocarcinoma corresponded with category N0 and N1 (p<0.01); similar tendency was typical for patients with undifferentiated cancer (p<0.01); for other morphological types these ratios were not significant (p >0.05) [6, 8].

In patients with adenocarcinoma, combined gastrectomy predominated over combined subtotal and proximal resection 4:2.5:1 (p<0.01); the same tendency was determined for other morphological types; the most expressed tendency was observed in patients with undifferentiated cancer – 6:5:1 [10].

The overall 5-year survival rate for all patients was 17.32±1.49%; for men – 16.11±1.72% (p=0.005), for women – 20.46±2.99% (p=0.399) (Table 1, Fig. 1); however, these differences were not statistically significant (p=0.087). As for the difference in the 5-year survival rate by morphology, the difference was significant between male patients with adenocarcinoma and undifferentiated cancer (17.52±2.05% and 12.53±3.27%, respectively p=0.041 [3]; in other cases, the 5-year survival was not achieved (Table 1, Fig. 2). In female patients, the highest 5-year survival was observed in patents with adenocarcinoma 24.69±3.96% (Table 1, Fig. 3), in patients with undifferentiated cancer – 11.47±4.06, there was no significant difference between them (p=0.502); in other cases, the 5-year survival rate was not reached.

Fig. 1.

Comparison of the distribution functions of survival by the histological type in patients who underwent combined surgery.

gmj-24-E201719-g1.jpg
Fig. 2.

Comparison of the distribution functions of survival by the histological type in male patients who underwent combined surgery.

gmj-24-E201719-g2.jpg
Fig. 3.

Comparison of the distribution function of survival by the histological type in female patients who underwent combined surgery.

gmj-24-E201719-g3.jpg

Conclusions

After surgery, there were no significant differences in the average life expectancy of patients with the same histological forms of SC between men and women (p>0.05), while significant differences were observed between patients (both men and women) with adenocarcinoma and undifferentiated adenogenic stomach cancer (p<0.05).

Taking into account the fact that combined surgery for SC is used mainly in older male patients, it should be considered in view of the current trend to the increase in the volume of surgery as well as the expansion of the indications for its performance.

Prospects for further research

Further researche should be directed to ascertain the survival of patients with locally advanced SC depending on the HER2 receptor expression of primary tumors.

References

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Copyright (c) 2017 Yuriy Yu Oliynyk, Roman Ro Slipetsky

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