In the past period, due to the rapid development of next-generation sequencing technology, accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response. More importantly, available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible. However, intricate complexities exist, and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment. The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development, and to highlight the relationship between gut microbes and the efficacy of immunotherapy, chemotherapy, radiation therapy and cancer surgery, which may provide insights into the formulation of individualized therapeutic strategies for cancer management. In addition, the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized. Although many challenges remain for now, the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies, and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.

Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

Objective: To evaluate the changes of esophagogastric junctional adenocarcinoma (EGJA) and gastroesophageal reflux disease (GERD) among surgical patients from 1988 to 2012 in a Chinese high-volume hospital. Background: The incidence of EGJA in Western countries has rapidly increased in recent decades. However, recent data from China remain sparse. Methods: A retrospective analysis was performed on the basis of 5053 patients who underwent surgery for gastric and distal esophageal adenocarcinoma. Total of 1723 patients with EGJA who underwent surgery were included. Changes of the prevalence of GERD and the clinicopathological features and surgical treatment of EGJA were longitudinally analyzed by a 5-year interval. Results: The proportion of EGJA was increased from 22.3% in period 1 (1988–1992) to 35.7% in period 5 (2008–2012) (P < 0.001). The proportion of Siewert type III (35.9% vs 47.0%) (P < 0.001) and type I (8.7% vs 15.8%) (P = 0.002) tumors of EGJA was also increased during the past 25 years. The prevalence of GERD had increased gradually from 6.5% in period 1 to 10.9% in period 5 for the 3 subgroups without significant difference (P = 0.459). There was an upward tendency with significant difference between the proportion of EGJA and the prevalence of GERD (r = 0.946, P = 0.000). Instead of type II and type III tumors, there was a positive correlation with change in GERD for type I tumors (r = 0.438, P = 0.029). Total gastrectomy was more preferred among patients with EGJA in period 5 than in period 1 (42.0% vs 19.6%) (P < 0.001). Conclusions: An increasing trend of EGJA is observed during the past 25 years in West China Hospital. The prevalence of GERD among EGJA had showed a gradually increased trend. However, the causality between GERD and EGJA still needs to be researched further. Total gastrectomy is becoming more preferred procedure in patients with EGJA.

Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.

This study aimed to investigate the impact of body mass index (BMI) on the short-term and long-term results of a large cohort of gastric cancer (GC) patients undergoing gastrectomy. Recently, the “obesity paradox” has been proposed, referring to the paradoxically “better” outcomes of overweight and obese patients compared with nonoverweight patients. The associations between BMI and surgical outcomes among patients with GC remain controversial. A single-institution cohort of 1249 GC patients undergoing gastrectomy between 2000 and 2010 were categorized to low-BMI (<18.49 kg/m²), normal-BMI (18.50–24.99 kg/m²), and high-BMI (≥25.00 kg/m²) groups. The postoperative complications were classified according to the Clavien-Dindo system, and their severity was assessed by using the Comprehensive Complication Index (CCI). The impact of BMI on the postoperative complications and overall survival was analyzed. There were 908, 158, and 182 patients in the normal-BMI, low-BMI, and high-BMI groups, respectively. The overall morbidity in the high-BMI group (24.7%) was higher than that in either the low-BMI or the normal-BMI group (20.9% and 15.5%, respectively; P = 0.006), but the mean CCI in the low-BMI group was significantly higher (8.32 ± 19.97) than the mean CCI in the normal-BMI and high-BMI groups (3.76 ± 11.98 and 5.58 ± 13.07, respectively; P < 0.001). The Kaplan–Meier curve and the log-rank test demonstrated that the low-BMI group exhibited the worst survival outcomes compared with the normal-BMI group, whereas the high-BMI group exhibited the best survival outcomes (P < 0.001). In multivariate analysis, BMI was identified as an independent prognostic factor. In the stage-specific subgroup analysis, a low BMI was associated with poorer survival in the cases of stage III–IV diseases. Low BMI was associated with more severe postoperative complications and poorer prognosis. Despite a higher risk of mild postoperative complications, the high-BMI patients exhibited paradoxically “superior” survival outcomes compared with the normal-BMI patients. These findings confirm the “obesity paradox” in GC patients undergoing gastrectomy.