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Clinical characteristics and outcomes for gastric cancer patients aged 18–30 years



There is little known about the clinicopathological features and the predictors of survival in extremely young adult patients aged 18–30 years. The aim of this study was to identify clinicopathological features and clinical outcomes for the overall population and for a resectable subgroup of gastric cancer patients aged 18–30 years.


From January 2004 to December 2010, 207 patients aged between 18 and 30 years old were diagnosed with gastric cancer and treated at the Asan Medical Center. Clinical findings, histopathological parameters and outcomes were reviewed retrospectively. Patients were further divided into 2 groups according to tumor resectability and then clinicopathological factors that affect tumor resectability and clinical outcomes were analyzed.


Clinicopathological characteristics of study population showed a predominance of females, undifferentiated tumors, diffuse-type cancers, and advanced gastric cancer. The overall resectability rate was 70.0 % and the median follow-up period was significantly longer in the resectable tumor group (P < 0.001). Significant prognostic predictors for overall survival in overall patients were higher CEA levels (P = 0.016), larger tumor size (P < 0.001), unresectability (P = 0.006), and presence of lymphovascular invasion (P = 0.012) in a multivariate analysis. Significant prognostic factors for overall survival in patients with resectable disease included larger tumor size (>4 cm), lymphovascular invasion and higher CEA level in the multivariate analysis.


Gastric adenocarcinomas in young adult patients aged 18–30 years have unique clinicopathological features. Early detection in a resectable state and subsequent complete resection could increase survival period in young patients with gastric cancer.


Gastric cancer (GC) is one of the most common malignancies in the world and is the second leading cause of cancer-related death worldwide [1]. Although GC incidence has steadily decreased over recent decades [2] and early detection with following treatment has progressed, it remains as a major clinical challenge. Optimal treatment modalities for GC include endoscopic resection and surgery, depending on the tumor stage and institutional criteria for selection of endoscopic resection. In cases where resection was curative, surgery produced excellent survival outcomes, with 5-year survival rates of up to 98 % in early gastric cancer (EGC) [3, 4]. Although there is currently no supporting evidence from randomized clinical trials, endoscopic resection has also shown similar clinical outcome to surgery [5, 6]. In advanced gastric cancer (AGC), surgical resection with lymph node dissection may offer the best chance for long-term survival [7, 8]. Since curative treatment is possible when tumors are resectable, screening modalities that can detect GC at a resectable stage could increase long-term GC survival rates.

Previous data have shown that GC occurs predominantly in older age groups, with a peak age at the sixth decade [9]. However, there has been some concern about a trend toward steadily increasing GC in young patients over the past few decades and studies were conducted to define the demographic, clinicopathologic and prognostic factors of GC in young patients [1012]. The incidence of GC in patients aged 40 years or younger ranges from 4.6 to 6.2 % [1214]. The clinicopathological features of GC in young patients are known to be different from older patients. Features reported more frequently in young patients compared with old patients included female predominance, a significantly higher proportions of Lauren’s diffuse-type cancers amongst all tumor types, and poorly differentiated histologic tumor types [1517]. Although some studies have analyzed GC characteristics in young patients [1012], there are currently no reported studies that evaluated GC in extremely young adult patients aged 30 years or younger. Thus, little is known regarding predictors of GC survival for this group or for the subgroups who underwent resection.

In our present study, we retrospectively reviewed our institution’s experience with gastric adenocarcinoma in young patients between 18 and 30 years of age that were treated between 2004 and 2010, specifically to define the contemporary clinicopathological characteristics and associated prognoses for this unique group of cancer patients. Additional analyses evaluated the factors for resectability and the predictors of survival in the subgroup of study patients who underwent resection.

Patients and methods


From January 2004 to December 2010, 281 patients between 18 and 30 years old were diagnosed with GC at Asan Medical Center, Seoul, Korea. Of these patients, 74 did not get any treatment neither underwent further evaluation in our institution for various causes; refusal of treatment itself, wish to be referred to one’s hometown care center for conservative management or wish to be referred to another tertiary care center for reconfirmation of diagnosis. Thus, these patients were excluded from this study due to insufficient data for analysis as well as loss to follow-up. The 207 total patients that were included in the analyses had a median age of 28 years old [interquartile range (IQR) range 25–29 years] and 126 patients (61 %) were female. In all cases, diagnosis was established based on the results from an upper gastrointestinal endoscopy and biopsy. Demographic data, clinical findings, histopathological parameters and outcomes were reviewed retrospectively based on the electronic medical record database. Patients were divided into 2 groups according to disease resectability based on TNM staging after evaluation of GC (resectable group versus unresectable group). Patient clinical outcomes were compared, and the clinicopathological factors and treatment modalities that affect tumor resectability and prognosis were analyzed. The flow chart is shown in Fig. 1. This study was approved by the Institutional Review Board of Asan Medical Center.

Fig. 1

Flow chart showing treatment modalities in the study subjects with GC aged 18–30 years


Resectable GC was defined as the absence of distant metastases, invasion of any major vascular structure including the aorta, disease encasement, or occlusion of the hepatic artery or celiac axis/proximal splenic artery. Macroscopic types of EGC were classified according to the classification of the Japanese Gastric Cancer Association [18] and tumor degree of differentiation was classified as recommended by the World Health Organization [19]. Well or moderately differentiated tubular cancers were classified as differentiated type, while poorly differentiated adenocarcinomas and signet ring cell carcinomas were classified as undifferentiated type [18].

In surgical cases, resection was considered complete when microscopic examination revealed a negative resection margin and no evidence of lymphovascular and perineural invasion. Resection was considered incomplete when microscopic examination revealed a positive tumor margin (R1) or residual gross disease (R2). Endoscopic resections were deemed curative when histologic examination showed that the lateral and vertical margins were free of tumor for a distance of >2 and >0.5 mm, respectively, and there was no evidence of submucosal invasion or lymphatic or vascular involvement. A positive family history of GC was defined as having one or more of first- or second-degree relatives with a history of GC diagnosed at any age.

Treatment protocols for GC at our institution

Endoscopic resection and surgery were performed in patients with resectable GC, while patients with unresectable GC were treated with chemotherapy or conservative disease management. Endoscopic resection was performed in selected cases of early GC when there was no evidence of lymph node metastasis and the indication criteria were met, including (1) mucosal cancers of any size without ulceration, and (2) mucosal cancers with ulcerations >30 mm or submucosal cancers less than 30 mm and confined to the upper 0.5 mm of submucosa without lymphovascular invasion [20, 21]. In endoscopic resection, the typical sequential procedure included marking, mucosal incision, and submucosal dissection with simultaneous hemostasis. After making several marking dots outside the lesion, saline containing epinephrine and indigo carmine was injected into the submucosal layer. A circumferential incision was made and submucosal dissection was performed to completely remove the lesion.

Gastrectomy was performed for patients who did not meet the criteria for endoscopic resection. Resection of both the tumor tissue plus appropriate lymph nodes was performed in cases of lymph node involvement or suspected lymph node metastasis during preoperative staging. Either subtotal or total gastrectomy was performed, depending upon the tumor location, and laparoscopic-assisted gastrectomy has been performed in our institute since 2004.

Statistical analysis

Baseline continuous and categorical variables are presented as the median with interquartile range (IQR) and number with percentage, respectively. Group comparisons of continuous variables were performed using Student’s t-tests, while categorical variables were compared with Fisher’s exact test or Pearson’s Chi-square test. Correlations between various factors and resectability were assessed by univariate and multivariate logistic regression analysis. Correlations between various factors and overall survival by GC were assessed by univariate and multivariate Cox proportional hazards regression analysis. Variables that were deemed of potential importance to the univariate analysis (P < 0.05) were included in the multivariate analysis. The final models were determined by backward variable selection, a method whereby the least significant variables are removed one at a time. All P values were two-sided, and P values <0.05 were considered to be statistically significant. Results for significant prognostic factors were expressed as the hazard ratio for each category and its 95 % confidence interval.

Patient survival was estimated using the Kaplan–Meier method and log-rank tests were used to evaluate differences in survival among different patient subgroups. The cut-off point for prediction of overall survival in continuous variables was assessed by the receiver operating characteristic curve (ROC) and area under the curve (AUC). Statistical analyses were performed using SPSS for Windows Version 19 (SPSS, Inc., Chicago, IL, USA).


Among the 207 patients in our present study cohort, the median age was 28 years (IQR 25–29 years). In our study population also, 54 patients were 25 years or younger and 2 patients were less than 20 years of age.

Baseline characteristics

Table 1 summarizes the patient overall clinical and histopathologic features. The majority of patients were female (60.9 %) and 40 patients (19.3 %) had a family history of GC. Most patients (n = 182, 87.9 %) had symptoms prior to GC diagnosis and the most commonly presented symptom was epigastric pain followed by dyspepsia.

Table 1 Patient overall and subgroup clinicopathologic features stratified by resectability

Advanced gastric cancer (n = 137, 66.2 %) was more common than EGC (70 patients, 33.8 %). With regard to histologic classification, the predominance of undifferentiated tumors (n = 196, 94.7 %) and diffuse-type cancers (n = 98, 81.0 %) was remarkable.

The distribution of clinical stages at diagnosis was as follows: stage IA, 62 patients (30.0 %); stage IB, n = 7 (3.3 %); stage IIA, n = 14 (6.8 %); IIB, n = 16 (7.7 %); IIIA, n = 10 (4.8 %); IIIB, n = 17 (8.2 %); IIIC, n = 20 (9.7 %); and IV, n = 61 (29.5 %).

Concerning the depth of tumor invasion, 67 patients (32.4 %) were diagnosed at T1 stage, 55 (82.1 %) of whom had mucosal cancer. In patients with a positive family history for GC, there were some tendencies towards smaller tumor size (3.6 versus 4.5 cm, P = 0.065) and lower death rate (32.5 versus 43.7 %, P = 0.196) compared to patients with a negative family history, although these differences were not statistically significant. There was also a trend toward a lower clinical stage at GC diagnosis in patients with a positive family history than in patients with a negative family history (P = 0.038).

Clinicopathologic features of GC in adult patients aged 18–30 years based on GC resectability

The clinical and histopathologic features of patients stratified according to disease resectability were shown in Table 1. The median follow-up period in patients with resectable disease was 64.0 months (IQR 40.0–94.0 months) and 10.5 months (5.8–18.0 months) in patients with unresectable disease. Survival was significantly longer in the resectable group than the unresectable group (P < 0.001). Patients in the resectable group also had higher BMIs (P = 0.004), hemoglobin levels (P = 0.006) and albumin levels (P < 0.001) than did the unresectable GC group. Although most of both group of patients had symptoms prior to diagnosis of GC, significantly larger portion of unresectable patients had symptoms than resectable patients (P = 0.038). However, when we analyzed associations between the specific symptoms and resectability, there were not significant differences (P = 0.711). Time to diagnosis from initial symptom was significantly longer in resectable group (8 versus 4 weeks, P < 0.001). A significantly higher percentage of unresectable GC group showed macroscopically AGC than was detected in the resectable GC group (P < 0.001).

Risk factors for GC resectability in adult patients aged 18–30 years

Table 2 shows the results of univariate and multivariate analyses for correlations between various clinicopathological factors and resectability. Among the clinical factors, the presence of GC-associated symptoms, shorter duration of symptoms, a lower BMI, alcohol consumption, lower levels of hemoglobin and albumin and higher levels of CA 19-9 increased the risk of unresectability. With regard to histopathologic factors, tumor location in lower third of the stomach, smaller tumor size and macroscopically EGC lowered the risk of unresectability. In multivariate analysis, macroscopically AGC [odds ratio (OR) 6.457, 95 % confidence interval (CI) 1.145–36.404, P = 0.035] and lower levels of albumin (OR 0.110, 95 % CI 0.037–0.325, P < 0.001) increased the risk of unresectability.

Table 2 Univariate and multivariate analyses of risk factors associated with resectability of GC in adult patients aged 18–30 years

Prognostic factors for GC survival in adult patients aged 18–30 years

In this study, surgery for GC was performed on 156 patients (75.4 %). Among them, 141 patients (90.4 %) underwent surgery with curative intent and the other 15 cases (9.6 %) underwent surgery with palliative intent. Among the 145 patients who underwent curative resection, 80 patients (55.2 %) showed complete resection, while R1 and R2 resection were performed in 64 patients (44.1 %) and 1 patient (0.7 %), respectively. There were 4 cases of recurrence in the completely resected patient cohort, with a median time to recurrence of 26.5 months (IQR 23.3–34.3) after surgery. Of the 4 patients who had an endoscopic resection (1.9 %), all cases were curative resections with no recurrence. The overall resectability rate was 70 % (145 patients), which was comprised of both surgery and endoscopic resection with curative intent.

Among our 207 study patients, 86 patients (41.5 %) died from disease-specific causes and there were no patients who died from other causes. Univariate analysis showed that the presence of GC-related symptoms, shorter duration of symptoms, a lower BMI, alcohol consumption, lower levels of hemoglobin and albumin, higher levels of CEA and CA 72-4, larger tumor size, tumor location other than the lower third of the stomach, total gastrectomy, unresectability, histologically diffuse tumor type according to Lauren’s classification and incomplete resection all increased death (Table 3).

Table 3 Univariate and multivariate analyses of prognostic factors for overall survival in adult patients with GC aged 18–30 years

In multivariate analyses, significant prognostic predictors were higher levels of CEA [hazard ratio (HR) 1.035, 95 % CI 1.006–1.064, P = 0.016], larger tumor size (HR 1.017, 95 % CI 1.008–1.025, P < 0.001), unresectability (HR 4.207, 95 % CI 1.514–11.690, P = 0.006) and presence of lymphovascular invasion (HR 2.657, 95 % CI 1.234–5.718, P = 0.012) (Table 3).

There were significantly different survival outcome according to these prognostic predictors. Receiver operating characteristic (ROC) curve analysis was conducted to identify optimal cut-off points for predictive of overall survival in two continuous variables, CEA and tumor size. For CEA, the AUC (area under the curve) was 0.612 (P = 0.010) and the cut-off point for prediction of survival was 1.45 ng/ml. For tumor size, the AUCs was 0.863 (P < 0.001) and the cut-off point for prediction of survival was 4.35 cm. Figure 2 shows Kaplan–Meier GC survival curve based on significant prognostic predictors for overall survival in study patients.

Fig. 2

Kaplan–Meier GC survival curve based on significant prognostic predictors for overall survival in study patients

In addition, we tried to analyze disease-free survival in entire study patient. There were 139 patients who were included in disease-free survival analysis. When we analyzed disease-free survival using Cox proportional hazards regression analysis, tumor size and macroscopically EGC type were significant predictive factors for survival in multivariate analysis (Table 4).

Table 4 Univariate and multivariate analyses of prognostic factors for disease-free survival in adult patients with GC aged 18–30 years

Clinical outcomes for patients with resectable GC aged 18–30 years

Among the 145 patients with resectable disease, 26 patients (17.9 %) died from disease-specific causes, with a median survival of 28.5 months (IQR 18.8–38.3). The other 119 surviving patients had a median survival of 79.0 survival months (IQR 51.0–98.0). Table 5 shows the results of univariate and multivariate analyses of prognostic factors for overall survival in patients with resectable GC aged 18–30 years. Significant prognostic factors for overall survival in resectable patients included tumor size (>4 cm) (P = 0.014), lymphovascular invasion (P = 0.016) and increased level of CEA in multivariate analysis.

Table 5 Univariate and multivariate analyses of prognostic factors for overall survival in patients with resectable GC aged 18–30 years


It has been suggested that GC in young patients has different clinical profiles and more aggressive tumor biology than conventional gastric carcinoma. These features include a predominance of female patients, genetics, and undifferentiated and diffuse histologic tumor types [12, 16, 22]. In the present study, we identified clinical and histopathological features associated with resectability and prognostic factors that influence the survival of patients with GC aged 18–30 years. This patient group showed female dominance, advanced stage cancer at diagnosis, and an undifferentiated histologic tumor type. In patients with resectable disease, larger tumor size (>4 cm), lymphovascular invasion and increased level of CEA were associated with poorer outcomes.

Generally, GC is more common in males than females, with a ratio in major surveys ranging from 1.1:1 to 2.3:1 [2, 23]. Several studies have shown a predominance of female patients in younger patient groups and a predominance of male patients in older patient groups [15, 17]. In our present study of young adults with GC, patients were predominantly female (60.9 %, 0.64:1). When analyses were repeated to include only patients aged 25 years or younger, female predominance was also noted (55.6 %, 0.80:1). This difference in the sex ratio can reflect a protective influence of estrogen against the induction of GC. According to the previous reports by La Vecchia [24] and Palli [25], risk for GC may increase after a short lifetime of estrogen influence, as was documented for early menopause and a short fertile period. Another possible mechanism for estrogen-mediated prevention of GC incidences is the reduction of gastric acid production. In an experiment on gastric acid secretion with regard to sex hormones, ovariectomy significantly increased parietal cell mass as well as basal acid secretion. Conversely, castration of male rats decreased both the number of parietal cells in the gastric mucosa and basal acid secretion [26]. These findings suggest that estrogen may play a role in the pathogenesis of GC. Other assumptions pertaining to female predominance in young patients include exposure to carcinogenic factors, which was more frequent and of longer duration in males than females [27]. Despite of this unique gender ratio, there are no known gender-related differences in GC patient prognosis [15, 17]. The present study showed that there were no gender differences between GC resectability and disease prognosis in young GC patients with resectable cancer. Further studies are needed to elucidate the mechanism of female predominance in young GC patients and to determine whether gender influences disease prognosis.

It is thought that GC may be the result of a combination of various environmental and genetic factors. A family history of GC is a well-established risk factor for this cancer. Family members of patients with GC are reported to have a 1.5- to 3-fold increased risk of also developing GC compared with family members of control subjects [2830]. Moreover, it is postulated that genetic factors may contribute more to GC in younger patients than in older patients, as young patients have less time of exposure to environmental carcinogens and other potential contributory factors [31, 32]. In our current study cohort, 19.3 % of our patients reported a positive family history of GC, which was higher than the historical overall value of 15 % [33]. Also it was notable that patients with a positive family history showed lower clinical stages of GC and smaller tumor sizes compared with patients with a negative family history.

Our present results also show that most patients (182 patients, 87.9 %) initially presented with symptoms prior to GC diagnosis. This finding is similar to other reports on young GC patients [13, 16] and it may be attributable to a lack of screening endoscopy in the typically asymptomatic young population. Population screening for GC varies between countries in both methods and screening intervals. In Japan, screening for GC is recommended for individuals older than 40 years and involves only a simple risk interview and barium studies. An upper endoscopy is performed if any abnormality is detected. In contrast, in Korea, GC screening every 2 years via either upper gastrointestinal series or upper endoscopy has been recommended for individuals aged 40 years and older. However, these screening criteria do not address populations younger than 40 years; thus, this subgroup of GC patients may be overlooked, leading to a potential delay in diagnosis and worse disease outcomes. Bołdys et al. [34] suggested that in areas of relatively high prevalence of GC, dyspeptic patients younger than 45 years and without alarm symptoms should undergo upper gastrointestinal endoscopy in order to avoid any potential delay in GC diagnosis. However, beyond evaluation of symptomatic patients, there should be increased and focused investigations designed to determine an optimal age threshold for screening endoscopy in the asymptomatic normal population. For early detection, symptomatic young patients should undergo upper gastrointestinal endoscopy, which could help prevent a delay in diagnosis and moreover facilitate adequate intervention and treatment of early stage disease.

With regard to GC histologic classifications, undifferentiated and Lauren classification diffuse type GCs predominated, with values of 94.7 and 81.0 %, respectively. Diffuse type adenocarcinoma develops following chronic inflammation without passing through a multistep progression including atrophic gastritis or intestinal metaplasia [31]. Diffuse type adenocarcinomas also have a clear hereditary form that results from E-cadherin deregulation upon genetic or epigenetic alterations [35]. Alternatively, the occurrence of intestinal type cancer is more frequently associated with environmental factors such as obesity, dietary factors, and cigarette smoking, as well as with infection by Helicobacter pylori [3638]. Our current findings suggest that GC in extremely young adult patients with diffuse-type tumor characteristics (98 patients, 81.0 %) likely have tumors that are closely associated with their genetic background. In our present study, a rapid urease test was performed in 15 patients and H. pylori IgG was checked in only 4 patients, so these data were insufficient for the evaluation of potential associations between H. pylori infection and GC histologic type.

In relation to tumor behavior, undifferentiated and diffuse histologic types are associated with biologically aggressive features [39]. However, our present data show that there were no differences in resectability or patient survival based on tumor survival. These findings suggest that although extremely young adult patients with GC typically have an aggressive tumor biology, if they are diagnosed at an early disease stage and then proceeded to surgical resection, the prognosis would be satisfactory. In patients with unresectable disease, a shorter time to diagnosis from initial symptoms and lower levels of BMI and albumin were noted in comparison with patients with resectable disease. This suggests that unresectable GCs of an advanced stage in young adults have an aggressive behavior, showing rapid progression without warning symptoms therefore leading to malnutrition.

There were some notable limitations to this study. The major limitation was its retrospective design. Also, since our hospital is a tertiary referral center, some patients may be diagnosed late due to low accessibility, leading to a potential delay in treatment and thus altering their prognosis. Another important limitation is that this study only analyzed data from a group of young patients with GC. Nevertheless, our analyses revealed important clinicopathological features and outcomes as the first study that reviewed GC in adult patients aged 18–30 years. Further studies are needed to elucidate the unique features and outcomes of younger patients compared with older age groups.

In conclusion, gastric adenocarcinomas in young adult patients aged 30 years or younger have unique clinicopathological features such as female dominance, advanced stage cancer, and undifferentiated and diffuse histologic type. Although GCs in young patients display an aggressive tumor biology, early detection in a resectable state and subsequent complete resection without lymphovascular invasion could increase the survival period for young adults with GC.


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Correspondence to Hwoon-Yong Jung.

Additional information

H. J. Park and J. Y. Ahn contributed equally to this work as co-first authors.

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Park, H.J., Ahn, J.Y., Jung, HY. et al. Clinical characteristics and outcomes for gastric cancer patients aged 18–30 years. Gastric Cancer 17, 649–660 (2014).

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  • Gastric cancer
  • Young
  • Prognosis