Prognostic Impact of Stromal Profiles Educated by Gastric Cancer.

BACKGROUND: Cancer-associated fibroblasts exhibit diversity and have several subtypes. The underlying relationship between the diversity of cancer-associated fibroblasts and their effect on gastric cancer progression remains unclear. In this study, mesenchymal stem cells were differentiated into cancer-associated fibroblasts with gastric cancer cell lines; clinical specimens were used to further investigate the impact of cancer-associated fibroblast diversity on cancer progression. METHODS: Nine gastric cancer cell lines (NUGC3, NUGC4, MKN7, MKN45, MKN74, FU97, OCUM1, NCI-N87, and KATOIII) were used to induce mesenchymal stem cell differentiation into cancer-associated fibroblasts. The cancer-associated fibroblasts were classified based on ACTA2 and PDPN expression. Cell function analysis was used to examine the impact of cancer-associated fibroblast subtypes on cancer cell phenotype. Tissue samples from 97gastric patients who underwent gastrectomy were used to examine the clinical significance of each subtype classified according to cancer-associated fibroblast expression. RESULTS: Co-culture of mesenchymal stem cells with nine gastric cancer cell lines revealed different subtypes of ACTA2 and PDPN expression in differentiated cancer-associated fibroblasts. Cancer-associated fibroblast subtypes with high ACTA2 plus PDPN expression levels significantly increased gastric cancer cell migration, invasion, and proliferation. The cancer-associated fibroblast subtype with ACTA2 plus PDPN expression was an independent prognostic factor along with lymph node metastasis for patients who had gastric cancer and were undergoing surgery. CONCLUSIONS: Cancer-associated fibroblasts are educated by gastric cancer cells during the development of cancer-associated fibroblast diversity. Differentiated cancer-associated fibroblasts with distinct expression patterns could affect gastric cancer progression and enable prognostic stratification for gastric cancer.

Clinical significance of postoperative complications after pancreatic surgery in time-to-complication and length of postoperative hospital stay: a retrospective study.

PURPOSE: We retrospectively analyzed pancreatectomy patients and examined the occurrence rate and timing of postoperative complications (time-to-complication; TTC) and their impact on the length of postoperative hospital stay (POHS) to clarify their characteristics, provide appropriate postoperative management, and improve short-term outcomes in the future. METHODS: A total of 227 patients, composed of 118 pancreaticoduodenectomy (PD) and 109 distal pancreatectomy (DP) cases, were analyzed. We examined the frequency of occurrence, TTC, and POHS of each type of postoperative complication, and these were analyzed for each surgical procedure. Complications of the Clavien-Dindo (CD) classification Grade II or higher were considered clinically significant. RESULTS: Clinically significant complications were observed in 70.3% and 36.7% of the patients with PD and DP, respectively. Complications occurred at a median of 10 days in patients with PD and 6 days in patients with DP. Postoperative pancreatic fistula (POPF) occurred approximately 7 days postoperatively in both groups. For the POHS, in cases without significant postoperative complications (CD ≤ I), it was approximately 22 days for PD and 11 days for DP. In contrast, when any complications occurred, POHS increased to 30 days for PD and 19 days for DP (each with additional 8 days), respectively. In particular, POPF prolonged the hospital stay by approximately 11 days for both procedures. CONCLUSION: Each postoperative complication after pancreatectomy has its own characteristics in terms of the frequency of occurrence, TTC, and impact on POHS. A correct understanding of these factors will enable timely therapeutic intervention and improve short-term outcomes after pancreatectomy.

Differences in glycemic trends due to reconstruction methods after proximal gastrectomy from the perspective of continuous glucose-monitoring.

PURPOSE: In recent years, clinicians have focused on the importance of preventing hypoglycemia. We evaluated the impact of different reconstruction procedures after proximal gastrectomy on glycemic variability in non-diabetic patients with gastric cancer. METHODS: This prospective observational study was conducted between April 2020 and March 2023. Flash continuous glucose-monitoring, a novel method for assessing glycemic control, was used to evaluate the glycemic profiles after gastrectomy. A flash continuous glucose-monitoring sensor was placed subcutaneously at the time of discharge, and glucose trends were evaluated for 2 weeks. RESULTS: The anastomotic methods for proximal gastrectomy were esophagogastrostomy in 10 patients and double-tract reconstruction in 10 patients. The time below this range (glucose levels < 70 mg/dL) was significantly higher in the double-tract reconstruction group than in the esophagogastrostomy group (p = 0.049). A higher nocturnal time below this range was significantly correlated with an older age and double-tract reconstruction (p = 0.025 and p = 0.025, respectively). CONCLUSION: These findings provide new insights into reconstruction methods after proximal gastrectomy by assessing postoperative hypoglycemia in non-diabetic patients with gastric cancer.

Changes in and clinical utility of maximum phonation time and repetitive saliva swallowing test scores after esophagectomy.

BACKGROUND: Postoperative pneumonia in patients with esophageal cancer occurs due to swallowing dysfunction and aspiration. Recently, maximum phonation time (MPT) assessment and repetitive saliva swallowing test (RSST) have been focused on as swallowing function assessment methods that can identify patients as high risk for pneumonia. We aimed to evaluate the clinical utility of MPT assessment and RSST in patients undergoing oncological esophagectomy. METHODS: In total, 47 consecutive patients who underwent esophagectomy for esophageal cancer between August 2020 and July 2023 were eligible. The perioperative changes in MPTs and RSST scores were examined. In addition, univariate and multivariate analyses were performed to identify the predictive factors of postoperative pneumonia. RESULTS: The median MPTs before surgery and on postoperative days (PODs) 3, 6, and 10 were 18.4, 7.2, 10.6, and 12.4 s, respectively; postoperative MPTs were significantly lower than preoperative MPT. In addition, the MPT of POD 6 was significantly longer than that of POD 3 (P < 0.05). Meanwhile, there were no significant changes in perioperative RSST scores. Overall, 8 of 47 patients (17.0%) developed pneumonia postoperatively. A short MPT on POD 6 was one of the independent predictive factors for the incidence of postoperative pneumonia (odds ratio: 12.6, 95% confidence interval: 1.29-123, P = 0.03) in the multivariate analysis. CONCLUSIONS: The MPT significantly decreased after esophagectomy. However, the RSST score did not. The MPT on POD6 can be a predictor of postoperative pneumonia.

[A Case of Delayed-Onset Acute Interstitial Nephritis following Nivolumab Treatment in a Patient with Advanced Esophagogastric Junction Cancer].

An 81-year-old man with advanced esophagogastric junction cancer with paraaortic lymph node metastasis was treated with S-1 plus oxaliplatin and nivolumab combination chemotherapy. Subsequently, conversion surgery was performed, and the patient was discharged without postoperative complications. Two months after discharge, the patient developed fever, fatigue, and anorexia. Intravenous antibiotic therapy was started; however, the symptoms did not improve. Urine biochemical tests revealed significantly elevated N-acetyl-ß-D-glucosaminidase and ß-microglobulin levels, and acute interstitial nephritis was suspected. Steroid therapy was initiated, and the patient's symptoms improved. A renal biopsy performed at the same time the nivolumab treatment was initiated led to the diagnosis of immune-related interstitial nephritis, a probable adverse event of the treatment. Although immune-related adverse events associated with immune checkpoint inhibitors are typically colitis, interstitial pneumonia, and endocrine disturbances, we observed severe interstitial nephritis in the patient. Clinicians should also consider the possible occurrence of immune-related adverse events >2 months after administering treatment.

Clinical impact of gastrectomy for gastric cancer patients with positive lavage cytology without gross peritoneal dissemination.

BACKGROUND: The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established. PATIENTS AND METHODS: In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care. RESULTS: One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p < 0.001). CONCLUSION: Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Prognostic impact of lymph node micrometastasis in patients with gastric cancer.

PURPOSE: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of LNMM in patients with GC. METHODS: A total of 624 patients with pathologically lymph node metastasis-negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. RESULTS: Patients with lymph node tumors < 1500 µm in diameter (LNMM) had a significantly better prognosis than those with tumors ≥ 1500 µm in diameter (p = 0.012; log-rank test). Cox's proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for the overall survival of patients with pN1 GC. There was no significant difference in the overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). CONCLUSIONS: LNMM is associated with a favorable prognosis and maybe an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered a factor preventing adjuvant chemotherapy.

[Long-Term Prognosis of Patients with Biliary Tract Cancer Undergoing Pancreaticoduodenectomy].

We divided the patients with biliary tract cancer who underwent pancreaticoduodenectomy(PD)at our hospital into the 5-year recurrence-free and recurrence groups and investigated the prognostic factors. Additionally, we investigated the efficacy of adjuvant chemotherapy in patients with and without lymph node (LN) metastasis. There was no significant difference between the two groups for patient characteristics and perioperative factors. However, patients with LN metastasis tended to have a higher recurrence rate. For patients without LN metastasis, the median overall survival(OS)was not significantly different between the patients who received and did not receive adjuvant chemotherapy. For patients with LN metastasis, although it was not significantly different(p=0.234), the OS of patients who received adjuvant therapy was more than 3 times than that of patients who did not(58.6 months and 18.4 months, respectively). For patients with biliary tract cancer who underwent PD, positive LN metastasis may be a poor prognostic factor, and adjuvant therapy may possibly improve prognosis.

Platelets enhance malignant behaviours of gastric cancer cells via direct contacts.

In this study, we aimed to analyse human cancer cell-platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression. Various functional analyses of gastric cancer (GC) cells were performed after direct/indirect co-incubation with platelets derived from GC patients. Further detailed expression and signalling analyses were performed after co-culture with direct and indirect GC cells-platelet contact. Malignant behaviours of cancer cells, such as proliferation, migration, invasion and adhesion, were significantly enhanced after direct co-incubation with platelets. Microarray analyses demonstrated changes in multiple genes, including epithelial-mesenchymal transition (EMT)-related genes. Among them, matrix metalloproteinase 9 was notably upregulated, which was validated by quantitative reverse transcription-polymerase chain reaction and western blot. Further, this change was only observed after direct co-incubation with platelets. This study demonstrated that platelets from GC patients promote malignant behaviours of GC cells through EMT-related signalling, especially by direct contact with tumour cells.

Exposure to Blood Components and Inflammation Contribute to Pancreatic Cancer Progression.

BACKGROUND: Pancreatectomy is a highly invasive procedure with extensive intraoperative blood loss (IBL) and high risk of postoperative pancreatic fistula (POPF). We conducted an experimental and retrospective clinical study to determine whether the malignant behaviors of pancreatic cancer cells were enhanced by exposure to blood components in vitro and to evaluate the oncological significance of high IBL and POPF in pancreatic cancer. METHODS: This study included 107 patients undergoing radical pancreatectomy in the University of Yamanashi Hospital between 2011 and 2017, classified into high (n = 29) and low (n = 78) IBL groups. In vitro experiments included functional analyses of Panc-1 pancreatic cancer and normal mesothelial cells exposed to patient blood components, and clinical data were used to assess the contribution of IBL and POPF to patient outcomes. RESULTS: The migration (p = 0.007), invasion (p < 0.001), and proliferation (p < 0.01) of Panc-1 cells were enhanced with platelet coculture. The ability of Panc-1 cells to adhere mesothelial cells was enhanced by plasma coincubation, especially in the presence of inflammation (p < 0.001). High IBL was associated with worse overall survival (p = 0.007) and increased locoregional recurrence (p = 0.003) in patients. POPF enhanced the negative prognostic significance of high IBL (p < 0.001 for overall survival, p = 0.001 for locoregional recurrence), indicating the oncological negative effects of high IBL and POPF. CONCLUSIONS: Blood components, especially platelets, and inflammation enhance the malignant behaviors of pancreatic cancer cells, potentially contributing to poor prognosis for pancreatic cancer patients.

A grading system for predicting the prognosis of gastric cancer with liver metastasis.

OBJECTIVE: The prognosis of patients with liver metastases from gastric cancer is determined using tumor size and number of metastases; this is similar to the factors used for the prediction of liver metastases from colorectal cancer. The relationship between the degree of liver metastasis from gastric cancer and prognosis with reference to the classification of liver metastasis from colorectal cancer was investigated. METHODS: This was a multi-institutional historical cohort study. Among patients with stage IV gastric cancer, who visited the cancer hospitals in Fukushima Prefecture, Japan, between 2008 and 2015, those with simultaneous liver metastasis were included. Abdominal pretreatment computed tomography images were reviewed and classified into H1 (four or less liver metastases with a maximum diameter of ≤5 cm); H2 (other than H1 and H3) or H3 (five or more liver metastases with a maximum diameter of ≥5 cm). The hazard ratio for overall survival according to the H grade (H1, H2 and H3) was calculated using the Cox proportional hazards model. RESULTS: A total of 412 patients were analyzed. Patients with H1, H2 and H3 grades were 118, 162 and 141, respectively, and their median survival time was 10.2, 5.7 and 3.1 months, respectively (log-rank P < 0.001). The adjusted hazard ratio for overall survival was H1: H2: H3 = reference: 1.39 (95% confidence interval: 1.04-1.85): 1.69 (95% confidence interval: 1.27-2.27). CONCLUSIONS: The grading system proposed in this study was a simple and easy-to-use prognosis prediction index for patients with liver metastasis from gastric cancer.

Benefit of intensive chemotherapy for elderly patients aged 80 years or older with metastatic colorectal cancer: a state-wide multicenter cohort study.

BACKGROUND: It remains unclear whether intensive chemotherapy for Stage IV colorectal cancer (CRC) patients aged 80 years or older is beneficial prognostically. This study aimed to investigate the overall survival of Stage IV CRC patients aged ≥ 80 years receiving intensive chemotherapy. METHODS: The study design was a population-based, multicenter, historical cohort study. The extracted participants' data were consecutive patients diagnosed as Stage IV CRC between January 2008 and May 2015 in nine hospitals in Japan. Patients were classified into two groups according to age: aged group (≥ 80 years) and younger group (< 80 years old). Intensive chemotherapy was defined as at least two courses of doublet chemotherapy with oxaliplatin-or irinotecan-based regimens. The primary outcome was the adjusted hazard ratio (HR) of age ≥ 80 years in patients who undergoing intensive chemotherapy. RESULTS: During the study period, 1259 patients were treated for Stage IV CRC in the participating hospitals. In total, 231 patients (18.3%) were in the aged group, and 1028 (81.7%) were in the younger group, and 788 (62.6%) underwent intensive chemotherapy. The median overall survival for the aged and younger group patients was 21.0 months (interquartile range (IQR), 10.6-34.1 months) and 24.3 months (IQR 12.6-39.3 months), respectively. The adjusted HR of age ≥ 80 years was 1.29 (confidence intervals 0.84-2.00). CONCLUSION: Stage IV CRC patients aged 80 years or older receiving intensive chemotherapy had a similar prognosis to those aged < 80 years. Avoiding intensive chemotherapy for mCRC patients simply because they are ≥ 80 years old is not recommended.

[Pathological Complete Response of Intrapelvic Recurrence of Rectal Cancer after Chemoradiotherapy-A Case Report].

50's man who have performed anterior pelvic exenteration with lateral lymph node dissection for rectal cancer with pT4bN0M0, pStage Ⅱc about 2 years ago, was admitted to our hospital for the treatment of intrapelvic recurrence of rectal cancer. No distant metastasis was found in the computed tomography examination but the tumor invaded the dorsal side of the pubis. Because radical excision was impossible with these findings, he received chemoradiotherapy(CRT). Post-CRT imaging showed that the tumor of intrapelvic recurrence region reduced the size, and invasion of pubis had disappeared and been markedly reduced. Thus, radical excision seemed possible at this point, and we decided to attempt operation after total 6 weeks of S-1(120 mg/day)regimen and radiation(40 Gy/20 Fr). We performed Miles' operation. The final pathological examination demonstrated that no viable tumor cells remained in the resected rectum specimen, confirming that a pathological complete response(pCR)had been achieved.

Method for converting high-speed and spectrally efficient terahertz-wave signal into optical signal.

A simple method, which converts a high-speed and spectrally efficient on-off keying (OOK) signal in the terahertz (THz)-band into an optical signal, is reported. In the proposed method, the THz-wave signal is down-converted into a radio-frequency (RF) signal, which is transferred to an optical signal through an optical intensity modulator. This modulator's bias is set to a null point. An extracted optical sideband from the modulator output corresponds to the converted optical signal. When the intermediate frequency (IF) of the RF signal is set to more than or equal to half of the signal bandwidth, the method enables us to carry out proper conversion. The method is adequate for a spectrally efficient signal because the IF can be set to a low value. To show the method's validity, calculation, and some experiments using a signal shaped with a root Nyquist optical filter were carried out.

The Expression and Role of Aquaporin 4 in Colon Cancer.

BACKGROUND/AIM: Aquaporins (AQPs) were initially discovered as water channel proteins that facilitate transcellular water movements. Recent studies have shown that AQPs are expressed and play an oncogenic role in various cancers. However, the expression and role of Aquaporin 4 (AQP4) in colon cancer have not been investigated. This study aimed to examine the clinical and pathophysiologic significance of AQP4 in colon cancer. PATIENTS AND METHODS: Immunohistochemistry (IHC) of AQP4 for 145 primary tumor samples obtained from patients with stage II or III colon cancer was performed, and the relationship between AQP4 expression and patients' prognoses was analyzed. Knockdown experiments with AQP4 small interfering RNA using human colon cancer cells were conducted to analyze the effects on cell invasiveness. RESULTS: IHC revealed that AQP4 was scarcely expressed in the noncancerous colonic mucosa. Of the 145 patients who enrolled in this study, 109 (75.2%) and 36 (24.8%) patients were classified as negative and positive for AQP4 expression, respectively. A high level of AQP4 expression is significantly associated with deeper tumors with lymph node metastasis and venous invasion. A 5-year progression-free survival rate of AQP4-positive patients was significantly worse than that of AQP-4 negative patients (70.7% vs. 87.0%, p=0.049). Furthermore, AQP4 knockdown significantly inhibited cell migration and invasion in HCT116 cells. CONCLUSION: AQP4 may be a novel biomarker and therapeutic target for colon cancer.

Investigating Cytoglobin Expression in Colon Cancer: Clinicopathological Insights from Immunohistochemical Analysis.

BACKGROUND/AIM: Cytoglobin (Cygb), a protein involved in cellular oxygen metabolism and protection, has garnered attention owing to its potential role in the initiation and progression of cancer, particularly colon cancer (CC). This study investigated the expression and significance of Cygb in CC. PATIENTS AND METHODS: This study included 145 patients who underwent R0 surgery for CC (clinical stage II/III) at our institution between January 2007 and December 2014. Immunohistochemical analysis was performed to evaluate the Cygb expression patterns in CC tissues. Additionally, the correlation between Cygb expression levels and the clinicopathological characteristics of patients with CC was investigated. RESULTS: Colon cancer tissues were categorized into high-expression (95 cases) and low-expression (50 cases) groups. Cygb was highly expressed in well-differentiated cases, whereas its expression decreased in poorly differentiated cases. No significant differences in other clinicopathological factors were observed between the two groups. Cygb expression had no significant effect on recurrence-free survival or overall survival. CONCLUSION: This study contributes to the growing understanding of Cygb expression and its significance in CC. The expression of Cygb in CC was found to be unrelated to the recurrence rate and prognosis, but showed a correlation with differentiation status.

Re-consideration of Lymph Node Metastasis in Pancreatic Cancer Patients Following Radical Resection: A Retrospective Study.

BACKGROUND/AIM: Perioperative chemotherapy has become more common in patients with pancreatic cancer (PC), and the significance of lymph node (LN) metastasis and the role of surgical resection in PC have gradually evolved. In the present study, we reconsidered the significance of LN metastasis for patients with PC. PATIENTS AND METHODS: We analyzed 142 PC patients who underwent radical resection at our hospital between September 2012 and December 2021. Patients were divided into three groups based on the performance of preoperative chemotherapy, as follows: up-front surgery (US, n=109), neoadjuvant chemotherapy (NAC, n=22), and conversion surgery (CS, n=11). The characteristics of patients with LN metastasis in the US group were clarified, and a prognostic analysis was performed. The prognostic impact of LN metastasis in the NAC/CS group was examined and compared to that in the US group. RESULTS: Multivariate analysis revealed that high CA19-9 levels, large tumor size, and positive lymphatic invasion were significantly associated with LN metastasis. LN metastasis and portal vein invasion were independent poor prognostic factors in multivariate analysis. Patients without LN metastasis in the NAC group tended to have a better prognosis than those in the US group; however, the prognosis of patients with LN metastasis was similar between the two groups. In the CS and US groups, the prognosis was comparable for patients with and without LN metastasis. CONCLUSION: LN metastasis is a notably poor prognostic factor for PC patients, even after NAC, and more aggressive perioperative treatments may be considered for these patients.

The Prognostic Implications of Perioperative Serum Cholesterol Levels in Patients With Gastric Cancer.

BACKGROUND/AIM: Although cholesterol is an important indicator of nutritional status, it is also involved in cancer progression. In this study, we investigated the clinical significance of the dynamics of perioperative total cholesterol (T-Cho) levels in patients with gastric cancer (GC). PATIENTS AND METHODS: A total of 212 patients with pathological stage II/III disease who underwent gastrectomy between 2004 and 2020 were enrolled in this retrospective study. The preoperative and postoperative serum T-Cho levels were measured in these patients. RESULTS: Increased serum T-Cho levels were significantly correlated with low preoperative serum albumin levels (p<0.001). Patients with increased serum T-Cho levels after surgery had significantly lower overall and recurrence-free survival rates (p=0.030 and p=0.013, respectively; log-rank test). Cox proportional hazards model revealed that increased serum T-Cho levels (p=0.040), advanced pathological stage (p<0.001), and the provision of adjuvant chemotherapy (p=0.006) were independent prognostic factors for recurrence-free survival in patients with GC. CONCLUSION: Increased serum T-Cho levels after gastrectomy may be an independent prognostic factor in patients with GC.

Clinical Features and Survival of Young Adults with Stage IV Gastric Cancer: a Japanese Population-Based Study.

PURPOSE: With the aging of society, the mean age of patients with gastric cancer (GC) in Japan has increased. However, there are few documented outcomes for young patients with stage IV GC. We investigated the clinical characteristics and prognosis of such patients aged < 40 years using a dataset from an integrated population-based cohort study. METHODS: We conducted this multicenter population-based cohort study to determine whether earlier onset of GC was a poor prognostic factor. We enrolled patients with metastatic GC aged < 40 years (young group) and those aged between 60 and 75 years (middle-aged group). Patients were histologically diagnosed as having gastric adenocarcinoma. We evaluated the overall survival (OS) of both groups and the hazard ratio (HR) for OS based on age. The adjusted HR with 95% confidence interval (CI) was evaluated using the Cox proportional hazards model after adjusting for confounding factors, including sex, histology, number of metastatic lesions, surgical resection, and chemotherapy. RESULTS: This study enrolled 555 patients. The patients were classified into the young (n = 20) and the middle-aged group (n = 535). The median OS durations were 5.7 and 8.8 months in the young and middle-aged groups, respectively (p = 0.029). The adjusted HR (95% CI) of the young group was 1.88 (1.17-3.04, p = 0.009). CONCLUSION: Age was an independent prognostic factor in patients with stage IV GC. Further studies investigating the genomic characteristics of GC and exploring more effective chemotherapeutic agents are required.