Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis staging system.

The aim of this study was to determine the prognostic value of perineural invasion (PNI) in patients with gastric cancer who underwent curative resection. We retrospectively analyzed 518 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. Patients with PNI had a significantly larger tumors (≥5.0 cm), lymphatic venous invasion (positive), deeper tumor invasion (T4), more number of lymph node metastases (N3), and higher tumor stage (III). Regarding survival, multivariate analysis showed that PNI emerged as an independent prognostic factor for survival (hazard ratio (HR) = 1.901, P < 0.001). We incorporated the PNI into the 7th edition tumor-node-metastasis (TNM) staging system. Comparing with the 7th edition staging system, the redefinition of TPNI stage had higher -2loglikelihood value (-2loglikelihood = 3,492.259) and lower HR and 95 % confidence interval (CI) (HR = 1.955, 95 % CI = 1.630-2.343); redefinition of NPNI and TNMIIIPNI stage both had lower -2loglikelihood value (-2loglikelihood = 3,306.608; -2loglikelihood = 2,535.151) and higher HR and 95 % CI (HR = 1.879, 95 % CI = 1.720-2.053; HR = 2.268, 95 % CI = 1.900-2.707), which represented the optimum prognostic stratification, together with better homogeneity, discriminatory ability. Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer and it should be incorporated into TNM staging.

Node-extranodal soft tissue stage based on extranodal metastasis is associated with poor prognosis of patients with gastric cancer.

BACKGROUND: The purpose of this study was to evaluate the effect of Node-Extranodal soft tissue (pNE) stage based on Extranodal Metastasis (EM) on recurrence and survival in patients with gastric cancer (GC). MATERIALS AND METHODS: A total of 642 patients were divided into two groups according to statue of EM. Clinicopathologic features were compared among the two groups, the log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified by the Cox proportional hazards regression model. According to the number of EMs, EM was incorporated into the pN stage of gastric carcinoma. The 5-y overall survival (OS) and disease free survival (DFS) rates were 48.1% and 17.4%, 44.5% and 14.3% between the two groups. Patients with EM had a deeper tumor invasion and more number of lymph node metastases. Peritoneal dissemination and distant metastasis were more frequent with EM. EM is an independent risk factor for distance recurrence (odds ratio = 1.605), and it is the highest risk factor for peritoneal recurrence (odds ratio = 2.448). Multivariate analysis showed that depth of tumor invasion (P = 0.025), lymph node metastasis (P <0.001), and EM (P = 0.006) were independent factors associated with OS. Furthermore, EM (P = 0.0039) was also an independent prognostic factor for DFS. The differences in prognostic prediction between the seventh edition of the pN classification and the pNE classification were directly compared. We found the pNE classification (hazard ratio = 1.730, P <0.001) was more appropriate for predicting the OS of GC patients after curative surgery, and the -2 loglikehood of the pNE staging (4533.991) is smaller than the value of pN. CONCLUSIONS: EM was closely associated with cancer aggressiveness and the presence of EM was a significant independent predictor of reduced DFS and OS in GC patients. EM is an independent risk factor for distance recurrence, especially for peritoneal recurrence, the selection of postoperative adjuvant therapy in systemic (intravenous or intra-arterial) and regional (intraperitoneal) based on EM may be a reasonable approach. The lymph node imaging techniques such as injecting nanocarbon during surgery should be applied. As an important prognostic factor, EM should be incorporated into N stage according to its number retrieved in postoperative samples.

The role of preoperative neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after radical resection for gastric cancer.

The objective of this study was to investigate the impact of neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on the postoperative complication and long-term outcomes in patients with resectable gastric cancer (GC). A total of 377 patients who underwent curative resection for GC were enrolled. In logistic analysis, PLR (p = 0.09) was independently associated with the incidence of postoperative complication. The results of multivariate survival analysis showed the NLR and PLR were introduced as prognostic factors for operable GC, the NLR may represent a useful prognostic index for the prediction of overall survival (OS) in advanced GC (p = 0.021).

[The prognostic analysis of tumor size in T4a stage gastric cancer].

OBJECTIVE: To investigate the impact of tumor size in the prognosis of T4a stage gastric cancer. METHODS: The best cut-off point depending on tumor size was selected by Kaplan-Meier. Compare cliniclópathological characteristics between small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate analysis was done by Log-rank test and multivariate analysis was performed using the Cox proportional hazard regression model. The independent prognostic factors of patients were performed subgroup analysis. RESULTS: Eight centimetre was the optimal cut-off of tumor size for T4a stage gastric cancer. There were significantly differences between SSG and LSG in tumor location (χ² = 15.695), histological grade (χ² = 4.393), macroscopic type (χ² = 5.629) and early recurrence (χ² = 4.292). Univariate analysis showed age (χ² = 4.463), tumor size (χ² = 9.057), macroscopic type (χ² = 6.679), histological grade (χ² = 5.122), location of tumor (χ² = 8.707) and N stage (χ² = 132.954) are related to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192) were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR = 1.876) was independent risk factor for survival (P = 0.000). Further stratified analysis indicated that the 5-year survival rate of LSG is significantly lower than that of SSG in T4a stage patients of gastric cancer without lymph nodes metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01). CONCLUSIONS: Tumor size is an independent prognostic factor in patients of T4a stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant impact on the prognosis of T4a stage gastric cancer without lymph nodes metastasis or poorly differentiated.

[The significance of No.13 lymph node dissection in D2 gastrectomy for lower-third advanced gastric cancer].

OBJECTIVE: To evaluate the feasibility and necessity of No.13 lymph node dissection in D2 radical gastrectomy for lower-third advanced gastric cancer (AGC). METHODS: Data of 379 cases who were diagnosed as TNM II-III stage AGC were collected from January 2001 to June 2007. One hundred cases who undergone No.13 lymph node dissection during D2 gastrectomy for lower-third AGC were selected as study group. Other 279 cases (control group) received only D2 gastrectomy. The differences in clinicopathologic and intraoperative and postoperative parameters and 5-years survival rate were compared using the SPSS 17.0 software. RESULTS: There were no significant differences between the two groups in patients' gender, age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth, lymph node metastasis, TNM classification, operative time, blood loss and the incidence of postoperative complications (P > 0.05). In the study group, there were 9 patients with positive No. 13 lymph node, and its 5-year survival rate (46.0%) was higher than the control group (36.5%, χ² = 4.452, P < 0.05). The Univariate analysis showed that age (χ² = 7.539), No.13 lymph node dissection (χ² = 4.452), tumor size (χ² = 7.100), duodenum invasion (χ² = 9.106), tumor depth (χ² = 7.428), lymph node metastasis (χ² = 45.046), TNM classification (χ² = 57.008) are associated with prognosis of lower-third AGC (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 - 0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR = 5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 - 3.394) as independent prognostic factors (P < 0.05). CONCLUSION: No. 13 lymph node dissection for TNM II-III stage lower-third advanced gastric cancer is feasible and necessary.

[The value of negative lymph node count in prediction of prognosis of advanced gastric cancer].

OBJECTIVE: To evaluate the value of negative lymph node count (NLNC) in prediction of prognosis of advanced gastric cancer after radical resection. METHODS: The 544 cases of radical gastrectomy patients with complete clinical and follow-up data between January 2011 and July 2007 were collected. Survival was determined by the Kaplan-Merier method and univariate analysis was done by Log-rank test, Multivariate analysis was performed using the Cox proportional hazard regression model. RESULTS: Univariate analysis showed age (χ(2) = 4.449), T stage (χ(2) = 30.482), N stage (χ(2) = 205.452), location of tumor (χ(2) = 16.649), tumor size (χ(2) = 35.117), macroscopic type (χ(2) = 4.750), histological grade (χ(2) = 6.130), NLNC stage (χ(2) = 150.369) and type of gastrectomy (χ(2) = 25.605) were related to survival. Among them, T stage, N stage, tumor size and NLNC stage were independent risk factors for survival (P < 0.05). The prognostic factors of patients were performed subgroup analysis, NLNC > 15 group can prolong the survival than NLNC ≤ 15 group in the T2 stage (HR = 0.315), T4 stage (HR = 0.401), the same classification of location of tumor (HR = 0.286-0.493), tumor size (HR = 0.336, 0.465), macroscopic type (HR = 0.306, 0.418), histological grade (HR = 0.411, 0.365) and type of gastrectomy (HR = 0.444, 0.358 and 0.356, all P < 0.05). More NLNC can prolong Disease-Free Survival for patient of early recurrence (χ(2) = 8.648, P = 0.003). CONCLUSIONS: Sufficient negative lymph node count can prolong the survival and decrease the risk of early recurrence.

Examined lymph node count for gastric cancer patients after curative surgery.

Lymph node (LN) metastasis is the most common form of metastasis in gastric cancer (GC). The status and stage of LN metastasis are important indicators that reflect the progress of GC. The number of LN metastases is still the most effective index to evaluate the prognosis of patients in all stages of LN metastasis. Examined LN (ELN) count refers to the number of LNs harvested from specimens by curative gastrectomy for pathological examination. This review summarizes the factors that influence ELN count, including individual and tumor factors, intraoperative dissection factors, postoperative sorting factors, and pathological examination factors. Different ELN counts will lead to prognosis-related stage migration. Fine LN sorting and regional LN sorting are the two most important LN sorting technologies. The most direct and effective way to harvest a large number of LNs is for surgeons to perform in vitro fine LN sorting.

BMMSC-derived Exosomes Attenuate Cardiopulmonary Bypass-related Acute Lung Injury by Reducing Inflammatory Response and Oxidative Stress.

BACKGROUND: Acute lung injury (ALI), which is characterized by inflammation and oxidative stress, is a common complication after cardiopulmonary bypass (CPB). Exosomes from bone marrow mesenchymal stem cells (BMMSC-Exo) have recently been identified as promising treatments for ALI. However, the effects of BMMSC-Exo on inflammation and oxidative stress in CPB-related ALI remain unclear. OBJECTIVE: We aim to evaluate the effects of BMMSC-Exo on post-CPB ALI and explore their potential mechanisms. METHODS: We randomly divided rats into three groups: sham, ALI, and ALI+BMMSC-Exo groups. Histological changes were evaluated by lung histo-pathology and bronchoalveolar lavage fluid (BALF). ELISA assay was used to determine inflammatory cytokine levels and oxidative stress. RESULTS AND DISCUSSION: BMMSC-Exo attenuated histological changes (including the invasion of inflammatory cells), reduced the wet/dry (W/D) weight ratio, and downregulated inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1ß. BMMSC-Exo also alleviated oxidative stress. In vitro, we further administered lipopolysaccharide (LPS) to alveolar macrophages (AMs) to mimic the pathological changes of ALI and found that BMMSC-Exo suppressed reactive oxygen species (ROS) production and downregulated the levels of inflammatory cytokines. Mechanistically, BMMSC-Exo inhibited the phosphorylation of nuclear factor-κB (NF-κB), the nuclear translocation of p65, also facilitated the phosphorylation of Akt and the nuclear translocation of Nrf2, while upregulating the expression of HO-1. CONCLUSION: In summary, we indicate that BMMSC-Exo reduces CPB-related ALI by alleviating inflammation and oxidative stress. The underlying mechanism may involve the NF-κB p65 and Akt/Nrf2/HO-1 signaling pathways.

Standardizing the classification of gastric cancer patients with limited and adequate number of retrieved lymph nodes: an externally validated approach using real-world data.

BACKGROUND: Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. METHODS: All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N') resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. RESULTS: Significant difference in OS between the Limited and Adequate set (corresponding N0-N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N' classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N'0 = N0adequate + pT1N0M0limited, N'1 = N1adequate + N0limited (excluding pT1N0M0limited), N'2 = N2adequate + N1limited, N'3a = N3aadequate + N2limited, and N'3b = N3badequate + N3alimited). This N' classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN'M system over the 8th AJCC edition and was successfully validated using the SEER dataset. CONCLUSION: The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs.

Risk of station 12a lymph node metastasis in patients with lower-third gastric cancer.

BACKGROUND: Controversy over the issue that No. 12a lymph node involvement is distant or regional metastasis remains, and the possible inclusion of 12a lymph nodes in D2 lymphadenectomy is unclear. As reported, gastric cancer (GC) located in the lower third is highly related to the metastasis of station 12a lymph nodes. AIM: To investigate whether the clinicopathological factors and metastasis status of other perigastric nodes can predict station 12a lymph node metastasis and evaluate the prognostic significance of station 12a lymph node dissection in patients with lower-third GC. METHODS: A total of 147 patients with lower-third GC who underwent D2 or D2+ lymphadenectomy, including station 12a lymph node dissection, were included in this retrospective study from June 2003 to March 2011. Survival prognoses were compared between patients with or without station 12a lymph node metastasis. Logistic regression analyses were used to clarify the association between station 12a lymph node metastasis and clinicopathological factors or metastasis status of other perigastric nodes. The metastasis status of each regional lymph node was evaluated to identify the possible predictors of station 12a lymph node metastasis. RESULTS: Metastasis to station 12a lymph nodes was observed in 18 patients with lower-third GC, but not in 129 patients. The incidence of station 12a lymph node involvement was reported as 12.2% in patients with lower-third GC. The overall survival of patients without station 12a lymph node metastasis was significantly better than that of patients with station 12a metastasis (P < 0.001), which could also be seen in patients with or without extranodal soft tissue invasion. Station 12a lymph node metastasis and extranodal soft tissue invasion were identified as independent predictors of poor prognosis in patients with lower-third GC. Advanced pN stage was defined as independent risk factor significantly correlated with station 12a lymph node positivity. Station 3 lymph node staus was also proven to be significantly correlated with station 12a lymph node involvement. CONCLUSION: Metastasis of station 12a lymph nodes could be considered an independent prognosis factor for patients with lower-third GC. The dissection of station 12a lymph nodes may not be ignored in D2 or D2+ lymphadenectomy due to difficulties in predicting station 12a lymph node metastasis.

Advances in para-aortic nodal dissection in gastric cancer surgery: A review of research progress over the last decade.

Approximately 17%-40% of para-aortic lymph node (PAN) metastasis occurs in patients with advanced gastric cancer. As the third tier of lymphatic drainage of the stomach and the final station in front of the systemic circulation, PAN infiltration is defined as distant metastasis and plays a key role in the evaluation of the prognosis of advanced gastric cancer. Many clinical factors including tumor size ≥ 5 cm, pT3 or pT4 depth of tumor invasion, pN2 and pN3 stages, the macroscopic type of Borrmann III/IV, and the diffuse/mixed Lauren classification are indicators of PAN metastasis. Whether PAN dissection (PAND) should be performed on patients with or without the macroscopic PAN invasion remains unascertained, regardless of the numerous retrospective comparative studies reported on the improved prognosis over D2 alone. Another paradoxical result from many other studies showed no significant difference in the overall survival between these two lymphadenectomies. A phase II trial launched by the Japan Clinical Oncology Group indicated that two or three courses of S-1 and cisplatin preoperatively followed by radical surgery with D2 + PAND and postoperative S-1 is the current standard strategy for the treatment of patients with extensive lymph node metastasis, and this regimen could be substituted by a promising strategy with effective combination chemotherapy or suitable chemotherapy duration. This review focuses on the advances in radical gastrectomy plus PAND with or without chemotherapy for patients with advanced gastric cancer.

Bronchogenic cyst of the stomach: A case report.

BACKGROUND: Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions first reported in 1956; as of 2019, only 37 cases are available in the MEDLINE/PubMed online databases. BCs usually have no clinical symptoms in the early stage, and their imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination. CASE SUMMARY: A 55-year-old woman presented at our hospital with intermittent epigastric pain. She had a slightly high level of serum carbohydrate antigen 72-4 (CA 72-4). Endoscopic ultrasound found that a cystic mass originated from the submucosa of the posterior gastric wall near the cardia, indicating a diagnosis of cystic hygroma of the stomach. Furthermore, a computed tomography scan demonstrated a quasi-circular cystic mass closely related to the lesser curvature of the gastric fundus with a low density. Because the imaging examinations did not suggest a malignancy and the patient required complete resection, she underwent laparoscopic surgery. As an intraoperative finding, this cystic lesion was located in the posterior wall of the fundus and contained some yellow viscous liquid. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well with normal CA 72-4 levels, and her course was uneventful at 10 mo. CONCLUSION: This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this is the first case of BC to present with elevated CA 72-4 levels.

A Preliminary Study on the Establishment of the PDTX Model.

OBJECTIVE: The current study aims to explore the establishment of the patient-derived tumor xenograft (PDTX) model. MATERIALS AND METHODS: Twenty patients with gastric cancer, 10 males and 10 females, were enrolled in the current study. Firstly, the volume, invasion and metastasis of the xenografts were observed. Subsequently, the correlation between tumor tissues of the PDTX mouse model and the patients' primary tumor tissues was evaluated by pathological H&E staining and immunohistochemistry. RESULTS: The results showed that the PDTX models corresponding to 15 of the 20 patients were successfully established, and the success rate of PDTX model establishment was 75%. Furthermore, the PDTX models maintained the differentiation degree, morphological characteristics and structural characteristics of tumor cells. CONCLUSION: A PDTX model can be used as a substitute for cancer patients in clinical practice and may be suitable for clinical pharmacodynamic screening and new drug development.

Clinical significance of skip lymph-node metastasis in pN1 gastric-cancer patients after curative surgery.

BACKGROUND: In addition to the stepwise manner of lymph-node metastasis from the primary tumour, the skip lymph-node metastasis (SLNM) was identified as a low-incidence metastasis of gastric cancer (GC). So far, both the mechanism and outcome of SLNM have not been elucidated completely. The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis. METHODS: Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome. According to the pathological results, all GC patients who had lymph-node metastasis were categorized into three groups: patients with the perigastric lymph-node metastasis, patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results: Among the 505 GC patients who had lymph-node metastasis, 24 (4.8%) had pathologically identified SLNM. The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival (OS) (P = 0.194). The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC (P = 0.001). The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis (P < 0.001). The case-control matched logistic regression analysis results showed that tumour size (P = 0.002) was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery. Among the 19 pN1 GC patients with SLNM, 17 (89.5%) had metastatic lymph nodes along the common hepatic artery, around the celiac artery or in the hepatoduodenal ligament. CONCLUSIONS: SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.

The most appropriate category of metastatic lymph nodes to evaluate overall survival of gastric cancer following curative resection.

AIMS: The purpose of this study was to provide a nodal grouping category based on metastatic lymph nodes to evaluate overall survival in gastric cancer patients following curative resection (R0). PATIENTS AND METHODS: We reviewed data of 308 gastric cancer patients following curative resection to evaluate significantly survival differences in different categories of the number of metastatic lymph nodes. RESULTS: In 308 evaluable patients, 5-year survival rate (YSR) was 52.9% (median follow-up, 84 months; range, 6-144 months). A total of 6309 lymph nodes were harvested and examined from all 308 patients, and the average number of lymph nodes harvested for per patient was 20.5 (range, 15-49). The average number of metastatic lymph nodes was 5.4 (range, 0-37) per patient. The initial metastatic node cutoffs were designed as 0, 1-4, 5-8, 9-11, 12-16, and >or=17. According to this new category of the number of metastatic lymph nodes, the 5-YSR of various patient groups were 85.7%, 62.8%, 34.3%, 0%, 0%, and 3.4%, respectively. However, we found that there were not significant prognostic differences between patients with 9 metastatic lymph nodes and patients with more than 9 metastatic lymph nodes (P > 0.05). So we redesigned the later cutoffs of number of metastatic lymph nodes. They were as follows: 0, 1-4, 5-8, and >or=9 of metastatic lymph nodes. We demonstrated this new category of the number of metastatic lymph nodes was more appropriate to evaluate overall survival of gastric cancer patients following curative resection than anyone of the current metastatic lymph nodal stagings (such as N stag in UICC, location of metastatic lymph nodes in JCGC, or ratio of metastatic lymph nodes) by using the case-control matched fashion. CONCLUSIONS: Our new category of the number of metastatic lymph nodes was an important prognostic factor of gastric cancer patients following curative resection. There were significant overall survival differences in gastric cancer patient groups with various numbers of metastatic lymph nodes following curative resection.

Analysis of risk factors for the interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy.

AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.

Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th AJCC/UICC pTNM staging system for gastric adenocarcinoma: a multicenter study with external validation.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) pathological tumor-node-metastasis (pTNM) staging system may have increased accuracy in predicting prognosis of gastric cancer due to its important modifications from previous editions. However, the homogeneity in prognosis within each subgroup classified according to the 8th edition may still exist. This study aimed to compare and analyze the prognosis prediction abilities of the 8th and 7th editions of AJCC/UICC pTNM staging system for gastric cancer and propose a modified pTNM staging system with external validation. METHODS: In total, clinical data of 7911 patients from three high-capacity institutions in China and 10,208 cases from the Surveillance, Epidemiology, and End Results (SEER) Program Registry were analyzed. The homogeneity, discriminatory ability, and monotonicity of the gradient assessments of the 8th and 7th editions of AJCC/UICC pTNM staging system were compared using log-rank χ2, linear-trend χ2, likelihood-ratio χ2 statistics and Akaike information criterion (AIC) calculations, on which a modified pTNM classification with external validation using the SEER database was proposed. RESULTS: Considerable stage migration, mainly for stage III, between the 8th and 7th editions was observed in both cohorts. The survival rates of subgroups of patients within stage IIIA, IIIB, or IIIC classified according to both editions were significantly different, demonstrating poor homogeneity for patient stratification. A modified pTNM staging system using data from the Chinese cohort was then formulated and demonstrated an improved homogeneity in these abovementioned subgroups. This staging system was further validated using data from the SEER cohort, and similar promising results were obtained. Compared with the 8th and 7th editions, the modified pTNM staging system displayed the highest log-rank χ2, linear-trend χ2, likelihood-ratio χ2, and lowest AIC values, indicating its superior discriminatory ability, monotonicity, homogeneity and prognosis prediction ability in both populations. CONCLUSIONS: The 8th edition of AJCC/UICC pTNM staging system is superior to the 7th edition, but still results in homogeneity in prognosis prediction. Our modified pTNM staging system demonstrated the optimal stratification and prognosis prediction ability in two large cohorts of different gastric cancer populations.

A novel nomogram individually predicting disease-specific survival after D2 gastrectomy for advanced gastric cancer.

BACKGROUND: Few studies have shown nomograms that may predict disease-specific survival (DSS) probability after curative D2 gastrectomy for advanced gastric cancer (AGC), particularly among Chinese patients. This study sought to develop an elaborative nomogram that predicts long-term DSS for AGC in Chinese patients. METHODS: A retrospective study was conducted on 6753 AGC patients undergoing D2 gastrectomy between January 1, 2000 and December 31, 2012 from three large medical hospitals in China. We assigned patients from Sun Yat-sen University Cancer Center to the training set, and patients from the First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital to two separate external validation sets. A multivariate survival analysis was performed using Cox proportional hazards regression model in a training set, and a nomogram was constructed. Harrell's C-index was used to evaluate discrimination and calibration plots were used to validate similarities between survival probabilities predicted by the nomogram model and actual survival rates in two validation sets. RESULTS: The multivariate Cox regression model identified age, tumor size, location, Lauren classification, lymphatic/venous invasion, depth of invasion, and metastatic lymph node ratio as covariates associated with survival. In the training set, the nomogram exhibited superior discrimination power compared with the 8th American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.82 vs. 0.74; P < 0.001). In two validation sets, the nomogram's discrimination power was also excellent relative to TNM classification (C-index, 0.83 vs. 0.75 and 0.81 vs. 0.74, respectively; P < 0.001 for both). After calibration, the nomogram produced survival predictions that corresponded closely with actual survival rate. CONCLUSIONS: The established nomogram was able to predict 3-, 5-, and 10-year DSS probabilities for AGC patients. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacity, suggesting its clinical utility.

Selective tropism of liver stem cells to hepatocellular carcinoma in vivo.

AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC. METHODS: WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug. EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed. RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue. CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.