Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Genomic evolution and diverse models of systemic metastases in colorectal cancer.

OBJECTIVE: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing. DESIGN: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells. RESULTS: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2, which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells. CONCLUSION: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis.

Association of recurrent APOBEC3B alterations with the prognosis of gastric-type cervical adenocarcinoma.

OBJECTIVE: Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. METHODS: We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. RESULTS: Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). CONCLUSION: Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.

Assessment of indocyanine green fluorescence lymphography on lymphadenectomy during minimally invasive gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: In recent years, indocyanine green fluorescence lymphography has been introduced for lymphatic mapping in gastric cancer surgery. The aim of this study was to investigate the efficacy of ICGFL in lymph node dissection during minimally invasive surgery for gastric cancer. METHODS: A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed from the inception to January 2021 for all studies comparing ICGFL with non-ICGFL in GC patients undergoing minimal access gastrectomy. The primary outcome was the total number of harvested lymph nodes. The secondary endpoints were the number of metastatic LNs, operative time, estimated blood loss, and postoperative complications. The registration number of this protocol is PROSPERO CRD42020203443. RESULTS: A total of 13 studies including 1882 participants were included. In this meta-analysis, the use of ICGFL was associated with a higher number of harvested LNs (40.33 vs. 33.40; MD = 6.93; 95%CI: 4.28 to 9.58; P < 0.0001; I2 = 86%). No significant difference was found between the ICGFL and control groups in terms of metastatic LNs (2.63 vs. 2.42; MD = 0.21; 95%CI: -0.46 to 0.87; P = 0.54; I2 = 0%). In addition, the use of ICGFL could be safely performed without increasing the operative time (P = 0.49), estimated blood loss (P = 0.26) and postoperative complications (P = 0.54). CONCLUSION: The use of ICGFL may be a useful tool facilitating complete lymph node dissection during minimally invasive GC resection. However, more high-quality RCTs with large sample size are needed to validate this issue.

Clinical significance of lower perigastric lymph nodes dissection in Siewert type II/III adenocarcinoma of esophagogastric junction: a retrospective propensity score matched study.

PURPOSE: The optimal surgical procedure, whether total gastrectomy (TG) or proximal gastrectomy (PG), for Siewert type II/III adenocarcinoma of esophagogastric junction (AEG) has not been standardised, primarily because the optimal extent of lymph node (LN) dissection for AEG based on the metastatic rate of perigastric LNs remains under debate. The aim of this study was to investigate the metastatic incidence and prognostic significance of lower perigastric lymph nodes (LPLN), including No.4d, 5, 6 and 12a LN stations, in Siewert type II/III AEG. METHODS: A total of 701 patients with Siewert type II/III AEG who received transabdominal open gastrectomy (425 patients with TG and 276 patients with PG) from 2010 to 2015 in West China Hospital were retrospectively included. Based on the clinicopathological information of TG patients, the risk factors of LPLN-positive patients were evaluated, and the metastatic incidence as well as the therapeutic value (TV) index of each LN station was assessed. Moreover, the 5-year overall survival (OS) rates between LPLN-positive and LPLN-negative groups were compared in TG patients, and the postoperative survival difference between TG and PG patients was also compared, using propensity score matching (PSM) method. RESULTS: Tumour size (≥ 5 cm, OR = 1.481, p = 0.002) and pT stage (pT4, OR = 2.755, p = 0.024) were significant risk factors for patients with LPLN metastasis. For patients with tumour size more than 5 cm or pT4 stage, the metastatic rates of LPLN for Siewert type II, III and II/III AEG were 31.67%, 34.69% and 33.03%, whereas the TV indexes of LPLN for them were 5.76, 5.62 and 5.38, respectively. LPLN was a significant independent prognostic factor (HR = 1.422, p = 0.028), and positive LPLN was related to worse prognosis (p < 0.05). For patients with tumour size more than 5 cm or pT4 stage, TG patients were illustrated to have a better prognosis than PG patients, with 5-year OS rates of 58.9% vs 38.2% for Siewert type II AEG (χ2 = 4.159, p = 0.041), 68.9% vs 50.2% for Siewert type III AEG (χ2 = 5.630, p = 0.018) and 65.1% vs 40.3% for Siewert type II/III AEG (χ2 = 12.604, p < 0.001), respectively. CONCLUSIONS: LPLN metastasis is a poor prognostic factor for patients with Siewert II/III AEG. LPLN dissection may improve the long-term survival of patients with tumour size more than 5 cm or pT4 stage, and TG might be more suitable for this kind of cancer.

The long-term survival outcomes of gastric cancer patients with total intravenous anesthesia or inhalation anesthesia: a single-center retrospective cohort study.

BACKGROUND: The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA). METHODS: Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled. RESULTS: A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881-1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779-1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57-0.96 p < 0.01) and after PS matching cohort (HR: 0.65, 95% CI: 0.46-0.94, p < 0.01). CONCLUSIONS: Combined with the results of previous studies, total intravenous anesthesia has been shown to be superior to inhalation anesthesia in terms of overall survival for gastric cancer patients undergoing surgical treatment. The selection of intravenous or inhalation anesthesia for gastric cancer surgery should take into account the long-term prognosis of the patient.

Application of clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area, a propensity score matching study and comparison with open gastrectomy.

BACKGROUND: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. METHODS: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. RESULTS: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28-44.74 vs. 29, IQR 29-39.5, p = 0.002) and no. 9 station nodes (2, IQR 1-5 vs. 2, IQR 1-3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20-80 ml vs. 80, IQR 50-80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220-303.25 min vs. 232, IQR 220-255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7-9 days vs. 8, IQR 7-9 days, p = 0.452) were comparable between the CML and OG groups. CONCLUSION: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.

Indocyanine green fluorescence angiography prevents anastomotic leakage in rectal cancer surgery: a systematic review and meta-analysis.

BACKGROUND: The role of intraoperative use of indocyanine green (ICG) fluorescence angiography (ICGFA) to prevent anastomotic leakage (AL) in rectal cancer surgery remains controversial. METHODS: The systematic review for studies evaluating ICGFA in patients undergoing rectal cancer surgery in PubMed, Embase, Web of Science, and the Cochrane Library was performed up to April 30, 2020. The primary outcome was the incidence of AL. The analysis was performed using RevMan v5.3 and Stata v12.0 software. RESULTS: Eighteen studies comprising 4038 patients were included. In the present meta-analysis, intraoperative use of ICGFA markedly reduced AL rate (OR = 0.33; 95% CI: 0.24-0.45; P < 0.0001; I2 = 0%) in rectal cancer surgery, which was still significant in surgeries limited to symptomatic AL (OR = 0.44; 95% CI: 0.31-0.64; P < 0.0001; I2 = 22%). This intervention was also associated with shorter postoperative stays (MD = - 1.27; 95% CI: - 2.42 to - 0.13; P = 0.04; I2 = 60%). However, reoperation rate (OR = 0.61; 95% CI: 0.34-1.10; P = 0.10; I2 = 6%), ileus rate (OR = 1.30; 95% CI: 0.60-2.82; P = 0.51; I2 = 56%), and surgical site infection rate (OR = 1.40; 95% CI: 0.62-3.20; P = 0.42; I2 = 0%) were not significantly different between the two groups. CONCLUSION: The use of ICGFA was associated with a lower AL rate after rectal cancer resection. However, more multi-center RCTs with large sample size are required to further verify the value of ICGFA in rectal cancer surgery.

Comparisons of perioperative and survival outcomes of laparoscopic versus open gastrectomy for serosa-positive (pT4a) gastric cancer patients: a propensity score matched analysis.

BACKGROUND: Data about whether laparoscopic gastrectomy (LG) is applicable in serosa-positive (pT4a) gastric cancer patients remain rare. The purpose of this study is to compare the perioperative and long-term outcomes between the laparoscopic and open gastrectomy (OG) in pT4a gastric cancer patients who underwent curative resection. METHODS: A total of 1086 consecutive pT4a patients (101 patients with LG and 985 with OG) who underwent curative gastrectomy in a high-volume center between 2006 and 2016 were evaluated. Demographics, surgical, and oncologic outcomes were analyzed. Propensity score matching (PSM) analysis was performed to balance baseline confounders, and COX regression analysis was performed to identify independent prognostic factors. RESULTS: After PSM adjustment, a well-balanced cohort comprising 101 patients who underwent LG and 201 who underwent OG was analyzed. Operative time (288.7 vs. 234.2 min; P < 0.001) was significantly longer, while estimated blood loss (172.8 vs. 220.7 ml; P < 0.001) was significantly less in the LG group compared with the OG group. There were no significant differences between groups in total number of harvested lymph nodes, postoperative stays, readmission rate, and postoperative complication rate. The 3-year overall survival (OS) rate was not significant different in the LG and OG groups (66.7% vs. 62.8%, P = 0.668), and the subsequent multivariate analysis revealed that the surgical approach was not an independent prognostic factor for OS (HR = 1.123; 95%CI: 0.803-1.570; P = 0.499). In sensitivity analysis including 78 pairs well-matched patients operated by an experienced surgeon, the results were similar to these for the matched entire cohort. CONCLUSION: LG can be a safe and feasible approach for pT4a gastric cancer treatment. However, well-designed high-quality RCTs are expected to draw a definitive conclusion on this topic.

Closure of Petersen's defect in gastrectomy for gastric cancer: an interrupted time series analysis from a high-volume institution in China.

PURPOSE: Petersen's hernia (PH) is a serious complication after gastrectomy for gastric cancer. The aim of this study was to investigate whether closure of Petersen's defect (PD) can decrease the rates of PH and suspected Petersen's hernia (SPH). METHODS: Patients who underwent gastrectomy with PD were enrolled. From January 2014 to January 2017, we performed gastrectomy without PD closure (non-closure group). From February 2017 to June 2018, we closed PDs during gastrectomy (closure group). The rates of PH and SPH were compared between the two groups. The last follow-up was updated in August 2020. RESULTS: Among a total of 1213 patients, 12 patients (1.0%) developed PH, and 23 patients (1.9%) developed SPH. The rate of PH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 11/828, 1.3%, p = 0.042, log-rank test). The rate of SPH in the closure group was significantly lower than that in the non-closure group (1/385, 0.3% versus 22/828, 2.7%, p = 0.008, log-rank test). Non-closure of PD was a risk factor for PH and SPH (odds ratio (OR) 7.72, 95% CI 1.84-32.35, p = 0.006). CONCLUSIONS: PD closure is recommended after gastrectomy for gastric cancer, as the rates of PH and SPH were significantly decreased.

Laparoscopic infrapyloric lymph nodes dissection through the right bursa omentalis approach for gastric cancer.

BACKGROUND: A complete dissection of infrapyloric lymph nodes is the key to a curative gastrectomy, which can be sometimes technically challenging in laparoscopic surgery. METHODS: One hundred and eighteen patients with gastric cancer undergoing laparoscopic gastrectomy with D2 lymphadenectomy in which the infrapyloric lymph nodes were dissected through the right bursa omentalis approach were included. The clinicopathologic characteristics and surgical outcomes were analyzed retrospectively. RESULTS: The laparoscopic gastrectomy with D2 lymphadenectomy was successful in all 118 patients with no open conversion. The mean operation time was 246.6 ± 45.7 min. The mean estimated blood loss was 87.0 ± 35.9 mL. Postoperative complications occurred in 17.8% of the patients, which were treated successfully with conservative therapy or aspiration in all. There were no No.6 lymphadenectomy-associated complications, such as injury of transverse colon, vessels of mesocolon, pancreas or duodenum, no pancreatitis, pancreatic leakage or postoperative hemorrhage. The mean postoperative hospital stay was 9.6 ± 3.7 days. On average, the total lymph nodes harvested were 36.8 ± 12.9, in which the ones from the infrapyloric area were 5.1 ± 3.1. CONCLUSION: Laparoscopic dissection of infrapyloric lymph nodes through the right bursa omentalis approach seems to be feasible and safe, facilitating a more complete No.6 lymphadenectomy for gastric cancer.

[Utilizing Academic Clubs to Foster Practical Research Ability of Medical Students-Volunteer Team of Gastric Cancer Surgery of West China Hospital, Sichuan University].

The cultivation of medical students'research ability promotes in them high-quality career development. In addition to classroom instruction of the theoretical knowledge concerning research, the systematic training and practice of scientific research skills outside the classroom is also vitally important. We established the Volunteer Team of Gastric Cancer Surgery with the features of standardization, progressiveness, and practicality in order to cultivate the thinking skills concerning research and the research ability of medical students. Our team is supported by the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. Taking clinical and basic research skills training as the focus of our work, we have organized systematic workshops focused on theoretical knowledge and research skills practice programs of divers forms. Our work helps improve the research ability of medical students, suggesting that research-oriented clubs play an active role in the cultivation of practical research ability of medical students and should be widely promoted.

Is Preoperative Fibrinogen Associated with the Survival Prognosis of Gastric Cancer Patients? A Multi-centered, Propensity Score-Matched Retrospective Study.

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.

Development and validation of a nomogram for predicting overall survival of gastric cancer patients after D2R0 resection.

OBJECTIVE: The aim of the study was to find factors associated with overall survival (OS) and establish a nomogram predicting OS of patients with gastric cancer (GC) after D2R0 resection. METHODS: Demographic and clinicopathologic factors of patients with GC underwent D2R0 surgical resection were retrospectively collected from medical records, telephone interview or outpatient follow-up. To find factors significantly associated with OS, univariate and multivariate analyses were conducted. The concordance index (C-index) was used to measure the accuracy of the nomogram. Discrimination and calibration of the nomogram were tested using the patients in the validation set. RESULTS: Overall, patients with 890 GC underwent D2R0 surgical resection were included. Based on the results of univariate analysis and multivariate analysis, T stage, number of metastatic local lymph nodes, lymph node positive rate, adjuvant chemotherapy and diameter of tumour were used to construct a nomogram predicting OS of patients with GC after surgical resection. In the validation cohort, the C-index was 0.73 and the nomogram performed well in predicting OS. CONCLUSION: The nomogram was able to accurately predict OS of patients with GC underwent curative surgery and performed well in internal validation, which would also be useful for the decision-making of doctors.

Prognostic impact of Borrmann classification on advanced gastric cancer: a retrospective cohort from a single institution in western China.

BACKGROUND: Due to the controversy over the prognostic significance of Borrmann type in patients with gastric cancer (GC), the present study was to investigate the clinical value of Borrmann type in advanced GC. METHODS: We retrospectively evaluated 2092 patients with advanced GC and subsequently examined the clinicopathological characteristics and prognosis of patients stratified by Borrmann type. RESULTS: Patients were divided into three groups according to Borrmann type (Borrmann types I+II, III, and IV). Patients with Borrmann types III and IV had larger size, more poorly differentiated tumor type, more advanced tumor stage, and higher chance of involving the entire stomach. The overall survival (OS) rates were significantly different among the three groups (p < 0.001). Stratification analysis revealed significant OS rates among the three groups in tumor-node-metastasis (TNM) stage III (p < 0.001) and TNM stage IV (p = 0.008). Multivariate analysis revealed that Borrmann types, adjuvant chemotherapy, curative resection, and TNM stage were all independent predictors of OS among GC patients. The subgroup analysis indicated that Borrmann type was an independent predictor of OS among GC patients who undergone curative resection and with TNM stage III cancer. However, curative resection and postoperative chemotherapy failed to prolong the survival of patients with Borrmann type IV. CONCLUSIONS: The clinicopathological characteristics and prognosis of patients with three Borrmann types of GC were different. Borrmann type can be simply used as a valuable factor to predict survival in advanced GC patients, especially in those TNM stage III undergoing curative resection. Additionally, more attention should be paid to the treatment for Borrmann type IV GC.

Comparison between gastric and esophageal classification system among adenocarcinomas of esophagogastric junction according to AJCC 8th edition: a retrospective observational study from two high-volume institutions in China.

BACKGROUND: The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. METHODS: We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/ ). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). RESULTS: By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P < 0.001), TNM-EC (P = 0.001) in training cohort and TNM-GC (P < 0.001) TNM-EC (P < 0.001) in the validation cohort were both independent prognostic factors. The C-index value for the TNM-GC scheme was larger than that of TNM-EC system in both training (0.721 vs. 0.690, P < 0.001) and validation (0.721 vs. 0.696, P < 0.001) cohorts. After stratification analysis for Siewert type II, the C-index for TNM-GC scheme was still larger than that of TNM-EC in both training (0.724 vs. 0.694, P = 0.005) and validation (0.723 vs. 0.699, P < 0.001) cohorts. CONCLUSIONS: The 8th TNM-GC scheme is superior to TNM-EC in predicting the prognosis of AEG especially for type II among patients underwent transhiatal approaches.

"Four-Step Procedure" of laparoscopic exploration for gastric cancer in West China Hospital: a retrospective observational analysis from a high-volume institution in China.

BACKGROUND: The preoperative work-up has limitations on finding peritoneal dissemination (PD) in gastric cancer patients. Laparoscopic exploration (LE) can discover radiographically occult PD, obtain accurate stage and avert futile laparotomy. The aim of our study was to introduce "Four-Step Procedure" LE in West China Hospital and further evaluate its safety and feasibility. METHODS: We conducted a retrospective analysis on 165 patients from July 2016 to December 2017 who underwent "Four-Step Procedure" LE in gastrointestinal surgery department of West China Hospital. All the patients were diagnosed with gastric adenocarcinoma without explicit distant metastasis through Computed Tomography and/or Gastrointestinal Ultrasonography. Peritoneal lavage cytological examination (CY) was routinely performed during LE in our research. The "Four-Step" technical process of LE was introduced comprehensively. The clinicopathologic features and the presence of PD or CY at LE were analyzed, and the stratified analysis by cT and cN stages on the proportion of P1 and/or CY1 was also reported in this study. RESULTS: Total of 165 patients accepted LE in our study, among these patients: 27 (16.4%) patients with P1 and/or CY1: 19 (11.5%) patients were found PD (P1), 17 (10.3%) patients with positive cytological examination (CY1) and 9 (3.6%) patients with P1Cy1. The stratified analysis by cT stage indicated that there was no P1 and/or Cy1 in cT1-cT2 stages, 1 (2.7%) patient with P1 and 1 (2.7%) with Cy1 in cT3 stage, 18 (20.0%) patients with P1 and 16 (17.8%) with Cy1 in cT4 stage. After LE, there were 74 (44.8%) patients underwent laparoscopic assistant gastrectomy, 25 (15.2%) patients with open gastrectomy, 50 (30.3%) patients with neoadjuvant chemotherapy and 16 (9.7%) patients with palliative chemotherapy and/or conversion therapy. CONCLUSION: "Four-Step Procedure" LE is reliable and feasible for gastric cancer. From our study, LE has unique superiority on ascertaining PD and cytological examination and LE should be recommended in cT4 stage gastric cancer before resection.

Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis.

BACKGROUND: The tumor location-modified Lauren classification (mLC) has been proposed recently, but its clinical significance remains under debate. This study aimed to elucidate the clinical relevance of mLC and evaluate its superiority to the Lauren classification (LC) for gastric cancer patients with gastrectomy. METHODS: This study retrospectively evaluated 2764 consecutive gastric cancer patients from three comprehensive medical institutions. The patients were categorized into training, inner-validation, and independent validation sets. The relationships between mLC and other clinicopathologic factors were analyzed, and independent prognostic factors were identified. Survival prognostic discriminatory ability and predictive accuracy were compared between mLC and LC using the concordance index (C-index) and Akaike's information criterion (AIC), and a nomogram based on mLC was constructed to compare its prognostic improvement with the tumor-node metastasis (TNM) staging system. RESULTS: A significant association between mLC and gender, age, histologic type, T stage, N stage, and M stage was found. The findings showed that mLC, not LC, is an independent prognostic factor, with a smaller AIC and a higher C-index than LC. The nomogram based on mLC showed a better predictive ability than TNM alone. CONCLUSIONS: Compared with LC, mLC, which could be considered a more reliable prognostic factor, may improve the prognostic discriminatory ability and predictive accuracy for gastric cancer patients with gastrectomy.

Characteristics and survival outcomes related to the infra-pyloric lymph node status of gastric cancer patients.

BACKGROUND: To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients. METHODS: Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed. RESULTS: A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p <  0.001). CONCLUSIONS: Patients with no. 6 lymph node metastasis have poor survival outcomes. Complete infra-pyloric lymphadenectomy is necessary and crucial for gastric cancer patients.