Modified stomach-partitioning gastrojejunostomy for initially unresectable advanced gastric cancer with outlet obstruction: A case report.

BACKGROUND: Chemotherapy followed by gastrojejunostomy remains the main treatment for unresectable gastric cancer (GC) in the middle- or lower-third regions with gastric outlet obstruction (GOO). Radical surgery is performed as part of a multimodal treatment strategy for selected patients who respond well to chemotherapy. This study describes a case of successful radical resection with completely laparoscopic subtotal gastrectomy after a modified stomach-partitioning gastrojejunostomy (SPGJ) for obstruction relief, in a patient with GOO. CASE SUMMARY: During the initial esophagogastroduodenoscopy, an advanced growth was detected in the lower part of the stomach, which caused an obstruction in the pyloric ring. Following this, a computed tomography (CT) scan revealed the presence of lymph node metastases and tumor invasion in the duodenum, but no evidence of distant metastasis was found. Consequently, we performed a modified SPGJ, a complete laparoscopic SPGJ combined with No. 4sb lymph node dissection, for obstruction relief. Seven courses of adjuvant capecitabine plus oxaliplatin combined with Toripalimab (programmed death ligand-1 inhibitor) were administered thereafter. A preoperative CT showed partial response; therefore, completely laparoscopic radical subtotal gastrectomy with D2 lymphadenectomy was performed after conversion therapy, and pathological complete remission was achieved. CONCLUSION: Laparoscopic SPGJ combined with No. 4sb lymph node dissection was an effective surgical technique for initially unresectable GC with GOO.

The prognostic value of tumour-infiltrating lymphocytes, programmed cell death protein-1 and programmed cell death ligand-1 in Stage I-III triple-negative breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) represent a robust biological prognostic biomarker in triple-negative breast cancer (TNBC); however, the contribution of different subsets of immune cells is unclear. We investigated the prognostic value of immune markers, including stromal TILs (sTILs), CD8+T and FOPX3+T cells, PD-1 and PD-L1 in non-metastatic TNBC. METHODS: In total, 259 patients with Stage I-III TNBC were reviewed. The density of sTILs along with the presence of total (t), stromal (s), and intratumoral (i) CD8+T cells and FOPX3+T cells were evaluated by haematoxylin and eosin and immunohistochemical staining. Immunohistochemical staining of PD-1, PD-L1 was also conducted. RESULTS: All immune markers were positively correlated with each other (P < 0.05). In the multivariate analysis, sTILs (P = 0.046), tCD8+T cells (P = 0.024), iCD8+T cells (P = 0.050) and PD-1 (P = 0.039) were identified as independent prognostic factors for disease-free survival (DFS). Further analysis showed that tCD8+T cells (P = 0.026), iCD8+T cells (P = 0.017) and PD-1 (P = 0.037) increased the prognostic value for DFS beyond that of the classic clinicopathological factors and sTILs. CONCLUSIONS: In addition to sTILs, inclusion of tCD8+T, iCD8+T cells, or PD-1 may further refine the prognostic model for non-metastatic TNBC beyond that including classical factors alone.

Perioperative treatment and biomarker analysis of LP002, an anti-PD-L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer.

BACKGROUND: The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer. METHODS: We enrolled patients with resectable and PD-L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5-fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin-free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next-generation sequencing (NGS) with pre- and post-treatment tumor samples. RESULTS: Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow-up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty-four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1-3, including one achieving pCR. Twenty-seven patients had treatment-related adverse events (TRAEs), while grade 3-4 TRAEs were observed in 11 patients. No treatment-related deaths occurred. MIF staining revealed that TRG 1-3 group was associated with a higher density of PD-L1+/CD68+ cells in the pre-treatment tumor parenchyma than TRG 4-5 group (p = 0.048). NGS studies with paired pre- and post-treatment tumor samples revealed the disappearance of pre-existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1-3 (p = 0.0313). CONCLUSIONS: LP002 plus cisplatin and 5-fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages II and III gastric cancer.

BACKGROUND: The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated. AIM: To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients. METHODS: Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients. RESULTS: In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate (P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival. CONCLUSION: Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Adjuvant chemoradiotherapy vs adjuvant chemotherapy in locally advanced Siewert type II/III adenocarcinoma of gastroesophageal junction after D2/R0 resection.

BACKGROUND: For Siewert type II/III adenocarcinoma of gastroesophageal junction (AGE), the efficacy of adjuvant chemoradiotherapy (CRT) after D2/R0 resection remains uncertain. AIM: To determine whether CRT was superior to chemotherapy (CT) alone after D2/R0 resection for locally advanced Siewert type II/III AGE. METHODS: We identified 316 locally advanced Siewert type II/III AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018. 57 patients received adjuvant CRT and 259 patients received adjuvant CT. We followed patients for overall survival (OS), relapse-free survival, and recurrence pattern. RESULTS: Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9% (P = 0.010). Five-year OS rates of the CRT group and the CT group for Siewert type III AGE patients were 65.7% and 43.9% (P = 0.006). Among the 195 patients whose recurrence information could be obtained, 18 cases (34.6%) and 61 cases (42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively. The local and regional recurrence rates in the CRT group were lower than that in the CT group (22.2% vs 24.6%, 27.8% vs 39.3%). Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type III AGE. CONCLUSION: For locally advanced Siewert type III AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.

Can Gastric Cancer Patients with High Mandard Score Benefit from Neoadjuvant Chemotherapy?

A high Mandard score may indicate the tumor is insensitive to chemotherapy. We analyzed tumor regression and lymph node response under different Mandard scores to assess the impact of Mandard score on prognosis. Methods. Mandard scores and ypN stage of postoperative pathological reports were recorded. The results were reviewed by a professional pathologist. The radiologist compared the tumor regression before and after chemotherapy by computed tomography (CT). The survival of all patients was obtained by telephone follow-up. Multivariate Cox regression was used to assess the relationship between overall risk of death and Mandard score, imaging evaluation, and ypN stage. Results. In the Mandard score (4-5) group, the median survival time for PR and ypN0 patients was 68.5 and 76.7 months. While in the Mandard score (1-2) group, the median survival time for PD and ypN3a patients was 15.6 and 14.5 months. Imaging evaluation of tumor regression (PR 68.5 months, SD 27.8 months, and PD 10.2 months) and lymph node remission (ypN0 76.7 months, ypN1 61.6 months, ypN2 18.0 months, ypN3a 18.7 months, and ypN3b 18.3 months) showed improved survival. Mandard score, imaging evaluation, and ypN stage are important prognostic factors affecting prognosis. Conclusion. A high Mandard score does not mean neoadjuvant chemotherapy is ineffective in gastric cancer. Patients with imaging evaluation of tumor regression and ypN stage reduction may benefit from neoadjuvant chemotherapy.

Impact of mature tertiary lymphoid structures on prognosis and therapeutic response of Epstein-Barr virus-associated gastric cancer patients.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood. Methods: We retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively. Results: In our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups. Conclusions: Intratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.

Bioinformatics analysis of prognosis and immune microenvironment of immunological cell death-related gemcitabine-resistance genes in bladder cancer.

Background: Bladder cancer (BC) is the most common malignant tumor of the urinary system. Gemcitabine resistance partly accounts for treatment failure and recurrence in BC. Immunological cell death (ICD) is correlated with chemoresistance. The prognosis of patients with similar tumor stage still varies in response to chemotherapy, recurrence, and disease progression. Therefore, our study aimed to provide a prognostic model based on ICD-related and gemcitabine-resistance genes for BC. Methods: The data of BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs), and differentially expressed gemcitabine resistance-related genes (DEGRRGs) were identified using the edgeR package. The survival-associated DEGRRGs were identified by univariate Cox analysis. A prognostic model was established by univariate Cox regression analysis and validated by GEO dataset. The outcome of low-risk group and high-risk group was analyzed by the Kaplan-Meier curve. The relationship between risk score and immune cell infiltration was investigated using the TIMER online database. Results: The prognosis of patients in the ICD-high group was significantly better than ICD-low group. A prognostic model containing 5 gemcitabine resistance-related ICD-associated genes, including PTPRR, HOXB3, SIGLEC15, UNC5CL, and CASQ1, was established. In both TCGA prognostic model and GEO validation model, patients in the low-risk group had better outcomes than high-risk group. According to the receiver operating characteristic (ROC) curves, the risk score area under ROC curve (AUC) of the TCGA prognostic model were calculated to be 0.705, while the risk score of the GEO validation model were calculated to be 0.716. Patients in the high-risk group had a significantly higher immune score, stromal score, and infiltration of M0 macrophages, M1 macrophages, M2 macrophages, and activated CD4+ T cells. Patients in the high-risk group had significantly lower infiltration of the regulatory T cells, resting dendritic cell (DCs), and activated DCs. Conclusions: The present study highlighted the functional role of gemcitabine resistance-related ICD-associated genes, constructed a prognostic score for the outcome evaluation and searched for potential targets to overcome gemcitabine chemoresistance in BC.

Monoclonal antibody-based icELISA for the screening of diazinon in vegetable samples.

Diazinon (DAZ) is an organophosphorus pesticide (OP), which is commonly used to prevent and control harmful pests that endanger agricultural products. In this study, we developed a novel heterology coating strategy for the immunoassay of DAZ. The DAZ coating hapten can be directly conjugated to the carrier protein without requiring a spacer arm. This proposed hapten coating strategy is time-saving and significantly improves the sensitivity of the immunoassay due to the lack of a spacer arm. The as-synthesized coating antigen was used to screen the monoclonal antibody (mAb). Finally, the developed indirect competitive enzyme-linked immunoassay (icELISA) showed IC50 and limit of detection (LOD) values of 0.58 ng mL-1 and 8 pg mL-1, respectively. This method exhibited negligible cross-reactivity towards other analogues, and the recoveries of samples (cucumber, cabbage, and lettuce) ranged from 92.6% to 125.4%, with coefficients of variance (CV) below 12%. Good correlation between icELISA and high-performance liquid chromatography mass spectrometry (HPLC-MS/MS) was obtained. The proposed icELISA was an ideal tool for monitoring DAZ residues in food samples.