Current status of neoadjuvant immunotherapy for the treatment of gastric cancer.

Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024.

The "quadrant-sandwich" method in clockwise modular D2 lymph node dissection in laparoscopic total gastrectomy: a retrospective cohort study.

Background: For patients who need laparoscopic radical gastrectomy, lymph node dissection (LND) and optimization of surgical procedures are particularly important. This study introduces the "quadrant-sandwich" method in clockwise modular D2 LND and evaluates the advantages and safety of this method. Methods: The clinical data of 108 laparoscopic total gastrectomy patients admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed. Based on the different LND processes, 55 patients were allocated to the observation group, which underwent clockwise modular LND using the "quadrant-sandwich method", and 53 patients were allocated to the control group, which underwent traditional LND. The effectiveness and safety of the approach in terms of operation time, blood loss, lymph node yield, postoperative recovery and postoperative complications were observed in the two groups. Results: There was no statistical difference between the baseline data of the two groups. In relation to the surgery, the observation group had an operation time of 227.0±48.5 minutes, and intraoperative bleeding of 100.0 mL [inter-quartile range (IQR), 30.0-200.0 mL], while the control group had an operation time of 247±41.5 minutes, and intraoperative bleeding of 180.0 mL (IQR, 130.0-245.0 mL). There were statistically significant differences between the two groups in terms of the operation time and intraoperative bleeding (P=0.001, P=0.020). In relation to the LND, there were no statistically significant differences between the two groups in terms of the total number of lymph nodes in each division, and the number of positive lymph nodes. In relation to the post-operative results, there were no statistically significant differences between the two groups in terms of the post-operative pathological stage, first postoperative oral feeding, post-operative hospitalization time, and post-operative complications. Conclusions: Clockwise modular D2 LND using the "quadrant-sandwich method" is potentially safe and feasible in laparoscopic total gastrectomy. It not only ensures the thoroughness of the LND, but also ensures and efficient and fast surgical process, shortens the operation time, and reduces the amount of intraoperative bleeding.

Postoperative superior anastomotic leakage classification and treatment strategy for postoperative esophagogastric junction cancer.

Background: At present, anastomotic fistula cannot be avoided after adenocarcinoma of the esophagogastric junction (AEG). Once the anastomotic leakage occurs, the posterior mediastinum and the left thoracic cavity are often seriously infected, which further impairs respiratory and circulatory function, heightening the danger of the disease course. The aim of this study was to identify the characteristics of superior anastomotic leakage after surgery for AEG and recommend corresponding treatment strategies to improve the diagnosis and treatment of superior anastomotic leakage after surgery for AEG. Methods: The clinical data of 57 patients with superior anastomotic leakage after surgery for AEG in the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to March 2019 were retrospectively analyzed, including 27 cases referred from external hospitals and 30 cases at the Affiliated Cancer Hospital of Zhengzhou University. According to the diameter and risk level of anastomotic leakage, the high anastomotic leakage is divided into types I, II, III, and IV. Results: Patients with preoperative comorbidities or those treated with the transabdominal approach or laparoscopic surgery often had type I and type II anastomotic leakage; meanwhile, patients with preoperative comorbidities and sacral perforation or those treated with a thoracic and abdominal approach or open surgery often had type III and IV fistula. The difference between types I-II and types III-IV was statistically significant (P<0.05). The mortality rate of patients with type III and type IV leakage was 14.8% within 90 days after operation, while no deaths occurred among patients with type I and type II leakage, and the difference in mortality between the two groups was statistically significant (P<0.05). Conclusions: After surgery for AEG, suitable treatment measures should be adopted according to the type of superior anastomotic leakage that occurs. Types III and IV superior anastomotic leakages are associated with higher mortality and require greater attention from surgeons.

Retrospective study of combined pelvic exenteration in the treatment of primary and recurrent pelvic malignant tumors.

Background: Pelvic malignant tumors often originate in the rectum, bladder, uterus, and other organs. In patients with locally advanced tumours in the presence of direct invasion of one or more organs, negative tumor resection margin (R0) resection can be very beneficial to patient survival if it can be performed. As a multidisciplinary and high-risk surgical method, the pelvic exenteration (PE) procedure has only been reported in a few medical centres internationally. We retrospectively analyzed the clinical data of patients who had undergone PE surgery in our hospital, in order to provide ideas for the best treatment of patients with pelvic malignant tumors. Methods: A retrospective analysis was conducted of 59 patients with pelvic malignant tumors admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to July 2021, all of whom received PE surgery. They were divided into two groups according to the location of the disease: the rectal cancer group (n=40) and the cervical cancer group (n=19). Statistical analysis was performed on the baseline and follow-up data of the two groups of patients. Results: (I) Patient baseline data. Compared to the rectal cancer group, more patients in the cervical cancer group received preoperative radiotherapy and chemotherapy (P=0.013), and had a lower R0 resection rate (P=0.037). Postoperative complications in patients with rectal cancer and cervical cancer were 27.5% and 47.3%, respectively. (II) Patient survival analysis after PE surgery. The 5-year survival rate was 36.6% in the rectal cancer group and 25.3% in the cervical cancer group. In the rectal cancer group, for the primary tumor, if there was no lymph node metastasis or no postoperative complications in the postoperative pathology, the patient had a good survival prognosis. Univariate analysis showed that recurrent rectal cancer, postoperative lymph node metastasis, postoperative complications, and microsatellite stability (MSS) were significant predictors of poor survival outcomes. Multivariate analysis showed that lymph node metastasis and postoperative complications were independent prognostic factors for patient survival. Conclusions: PE is a viable option for pelvic malignancies; aggressive radical resection of lesions and reduced postoperative complications can effectively improve patient outcomes.

Clinicopathological features and prognoses in younger and older patients with mismatch repair defects colorectal cancer: a retrospective comparative cohort study.

Background: Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effects of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) patients. However, due to the low mutation rate of MSI-H/deficient mismatch repair (dMMR) in the overall population, some doctors are of the view that testing this indicator increases the burden on patients, and consequently some patients fail to receive the most beneficial treatment methods. In order to provide testing criteria for younger patients with a higher proportion of MSI-H, we designed this retrospective controlled study. Methods: A retrospective analysis was conducted of 1,901 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to December 2019 and underwent CRC-related gene testing. For this analysis, 100 patients aged 40 or younger are defined as the young group, and 305 patients aged 71 and older but younger than 80 are defined as the elderly group. We included patients who met the following criteria: (I) underwent preoperative colonoscopy or gastroscopy and were diagnosed with CRC; (II) received perioperative adjuvant therapy; (III) underwent curative surgery for CRC. Each patient was followed up from the time of surgery until April 30, 2023, or death, with follow-up visits scheduled every 3 months for the first 2 years after surgery, and every 6 months thereafter. Clinical characteristics such as age, gender, body mass index (BMI), tumor depth (T), number of metastatic lymph nodes (N), distant metastasis (M), tumor, node, metastasis (TNM) stage, extent of surgical resection, tumor size, tumor location, differentiation grade, and carcinoembryonic antigen (CEA) levels were collected. The microsatellite instability (MSI) status was analyzed using fluorescence in situ hybridization (FISH). Results: In young CRC patients, the proportion of MSI-H is higher than in elderly CRC patients (33% vs. 10.16%, P<0.001). The proportion of poorly differentiated tumors is also higher in young CRC patients compared to elderly CRC patients (53% vs. 31.15%, P<0.001). However, there were no significant differences in clinical characteristics between young and elderly CRC patients. In terms of prognosis, survival analysis of the young group showed that MSI status [hazard ratio (HR) =0.26, 95% confidence interval (CI): 0.08-0.88, P=0.03], TNM staging (HR =3.84, 95% CI: 1.38-10.71, P=0.010) were associated with the prognosis of CRC patients. Conclusions: The mutation rate of MSI-H is higher in young CRC patients compared to older. Our study further confirms that MSI-H can serve as a favorable prognostic marker for CRC patients. This finding may provide valuable guidance for clinicians in terms of prognosis assessment and treatment selection. If feasible, we hope that MSI testing can be performed for all CRC patients to enable targeted testing, with particular attention to monitoring the MSI status in young patients. This will aid clinicians in selecting appropriate treatment strategies for these patients.

The long-term outcomes and prognostic factors about locally advanced right colon cancer: a retrospective cohort study.

Background: The first case of treatment with en bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) for locally advanced right-sided colon cancer (LARCC) invading the pancreas, duodenum, or other organs, was reported in 1953 by Van Prohaska. Right-sided colon cancers invading the pancreas and duodenum are rare. Surgery can be technically challenging, with unclear oncologic consequences, hence there are few reports on the clinical outcomes and factors associated with survival in this patient cohort. The need for neoadjuvant chemotherapy in patients with LARCC is controversial, and the long-term survival of these patients as well as the preferred treatment regimen needs to be explored. This paper reports our experience in right hemicolectomy with en bloc resection for LARCC. We conducted this study to analyze the clinical features and surgical outcomes of LARCC. Methods: A retrospective study was performed using a database of all patients who underwent RHCPD due to the tumour directly invading the duodenum and/or pancreas in a 19-year period [2003-2022]. We included patients whose primary tumor site was the right hemicolon and who had undergone a negative tumor resection margin (R0) resection. In addition, the adhesions between the colon and other organs in these patients were malignant adhesions. The primary outcome was the overall survival after surgery. The secondary endpoints of the study included 30-day postoperative mortality, postoperative complications, prognostic factors, and tumour genetics. All patients were followed up with postoperative imaging at an interval of 3 months for the first 3 years and at an interval of 6 months for the next 2 years, and annual follow-up thereafter. Survival was estimated using Kaplan-Meier analysis. Variables with P values <0.05 in univariate analysis were entered into multivariate Cox proportional risk regression to identify independent predictors of survival. Results: There were 47 patients (23 males and 24 females) who underwent en bloc resection for LARCC. The median age of the patients was 61 years (range, 38-80 years). R0 resection was achieved in all cases. The overall complication rate was 27.7% (n=13). Two patients died within 30 days of surgery. The overall survival was 80.9%, 63.5%, and 51.7% at 1, 3, and 5 years, respectively. Univariate survival analysis identified pancreatic invasion, regional lymph node positivity, more than two organs invaded, and no neoadjuvant treatment as predictors of poor survival (log-rank P<0.05). Multivariate analysis showed that regional lymph node positivity [95% confidence interval (CI): 1.145-7.736; P=0.025] and more than two organs invaded (95% CI: 1.321-26.981; P=0.020) were predictors of poor survival. Conclusions: Relatively optimistic clinical outcomes from en bloc resection were demonstrated for patients with LARCC. For LARCC patients, en bloc resection can be carefully considered.

CD146 deficiency promotes inflammatory type 2 responses in pulmonary cryptococcosis.

Cryptococcus neoformans (C. neoformans) is an important opportunistic fungal pathogen for pulmonary cryptococcosis. Previously, we demonstrated that CD146 mediated the adhesion of C. neoformans to the airway epithelium. CD146 is more than an adhesion molecule. In the present study, we aimed to explore the roles of CD146 in the inflammatory response in pulmonary cryptococcosis. CD146 was decreased in lung tissues from patients with pulmonary cryptococcosis. Similarly, C. neoformans reduced pulmonary CD146 expression in mice following intratracheal inoculation. To explore the pathological roles of CD146 reduction in pulmonary cryptococcosis, CD146 knockout (KO) mice were inoculated with C. neoformans via intratracheal instillation. CD146 deficiency aggravated C. neoformans infection, as evidenced by a shortened survival time and increased fungal burdens in the lung. Inflammatory type 2 cytokines (IL-4, IL-5, and TNF-α) and alternatively activated macrophages were increased in the pulmonary tissues of CD146 KO-infected mice. CD146 is expressed in immune cells (macrophages, etc.) and nonimmune cells, i.e., epithelial cells and endothelial cells. Bone marrow chimeric mice were established and infected with C. neoformans. CD146 deficiency in immune cells but not in nonimmune cells increased fungal burdens in the lung. Mechanistically, upon C. neoformans challenge, CD146 KO macrophages produced more neutrophil chemokine KC and inflammatory cytokine TNF-α. Meanwhile, CD146 KO macrophages decreased the fungicidity and production of reactive oxygen species. Collectively, C. neoformans infection decreased CD146 in pulmonary tissues, leading to inflammatory type 2 responses, while CD146 deficiency worsened pulmonary cryptococcosis.

First- and Second-Line Treatments for Patients with Advanced Hepatocellular Carcinoma in China: A Systematic Review.

Chinese national guidelines recommend various systemic therapies for patients with advanced hepatocellular carcinoma (HCC), but optimal treatment selection remains uncertain. To summarize the evidence supporting the systemic treatment of Chinese patients with advanced HCC, we performed a systematic review using a literature search of PubMed, Embase, China National Knowledge Infrastructure, and the Chinese Scientific Journal Database between 1 January 2009 and 15 June 2021, and abstracts from ASCO 2020, ASCO GI 2021, ESMO 2020, and ESMO GI 2020. The inclusion criteria were: Chinese patients aged ≥18 years with advanced HCC; first- or second-line systemic therapy; an evaluation of the efficacy or safety outcomes; and a randomized controlled, non-randomized controlled, prospective, or retrospective design. Thirty reports were identified for the following therapies: the single-agent tyrosine kinase inhibitor (TKI; n = 10), single-agent programmed death-1 (PD-1) inhibitor (n = 4), chemotherapy (n = 5), PD-1/programmed death-ligand 1 (PD-L1) inhibitor plus TKI (n = 6), PD-1/PD-L1 inhibitor plus bevacizumab or biosimilar (n = 4), and PD-1/PD-L1 inhibitor plus chemotherapy (n = 1). The heterogeneity between the studies precluded statistical analysis and the data were summarized using tables. In the first-line setting, evidence supported the use of atezolizumab or sintilimab plus bevacizumab or a biosimilar. There remains insufficient evidence to determine the optimal approved TKI-based therapeutic option, and active controlled trials in the second-line setting were lacking.

Selection of Digestive Tract Reconstruction After Partial Gastric Sparing Surgery in Patients With Adenocarcinoma of the Esophagogastric Junction of cT2-T3 Stage.

Objective: To investigate the appropriate reconstruction method of the digestive tract after partial gastric sparing surgery for adenocarcinoma of the esophagogastric junction of stage cT2-T3. Methods: A retrospective analysis of the clinical data of patients with adenocarcinoma of the esophagogastric junction from January 2015 to January 2019 in the General Surgery Department of Zhengzhou University Affiliated Tumor Hospital was performed. Patients with intraoperative double tract anastomosis composed the double tract reconstruction (DTR) group, and patients with intraoperative oesophagogastrostomy with a narrow gastric conduit group composed the oesophagogastrostomy by a narrow gastric conduit (ENGC) group. We analysed and compared the short-term postoperative complications and long-term postoperative nutritional status of the two groups of patients. Result: There were no statistically significant differences between the two groups of patients in terms of age, sex, preoperative haemoglobin level, albumin level, cT, cN, neoadjuvant therapy or not, pathological type and Siewert type. In terms of BMI and body weight, the ENGC group was higher than the DTR group, but the difference was not statistically significant (p = 0.099, p = 0.201). There was no significant difference between the two groups of patients in terms of upper resection margin, operation time, blood loss, tumor diameter, pT, pN and postoperative hospital stay. The gastric resection volume of the DTR group was much larger than that of the ENGC group, and there was a significant difference between the two (p = 0.000). The length of the lower resection margin of the DTR group was also significantly greater than that of the ENGC group (p = 0.000). In terms of surgical approach, the proportion of the DTR group with the abdominal approach was significantly higher than that of the ENGC group, and the difference between the two was statistically significant (p = 0.003). The postoperative exhaust time in the ENGC group was significantly shorter than that in the DTR group (p = 0.013). However, there was no statistically significant difference between the two groups in terms of anastomotic leakage, anastomotic bleeding, intestinal obstruction, abdominal infection, pneumonia, pancreatic leakage, lymphatic leakage,death within 30 days after surgery, or overall complications. In terms of anastomotic stenosis, the incidence in the ENGC group was higher than in the DTR group, and the difference was statistically significant (p = 0.001). There was no significant difference in oral PPI, haemoglobin or albumin levels in patients at 3 months, 6 months, or 12 months after surgery. Comparing reflux/heartburn symptoms at 3 months and 6 months after surgery, we found no statistically significant difference between the two, while in terms of reflux/heartburn symptoms at 12 months after surgery, the findings of the ENGC group were higher than those of the DTR group, and the difference was statistically significant (p = 0.045). In terms of poor swallowing, the ENGC group was always higher than the DTR group, and the difference between the two groups was statistically significant (p < 0.05). There was no statistically significant difference in body weight between the two groups at 3 months or 6 months after surgery. At 12 months after surgery, the body weight of the patients in ENGC group was significantly higher than that in the DTR group, and the difference between the two groups was statistically significant (p = 0.039). Conclusions: For patients with cT2-T3 stage oesophagogastric junction adenocarcinoma with tumours less than 4 cm in diameter, ENGC anastomosis is recommended for patients with a high tumour upper boundary, with obesity, short mesentery, or disordered vascular arch, and for routine patients, DTR anastomosis is recommended.

Metabolic cross-talk between ovarian cancer and the tumor microenvironment-providing potential targets for cancer therapy.

Conventional treatments for ovarian cancer, including debulking cytoreductive surgery combined with carboplatin/paclitaxel-based chemotherapy, are insufficient, as evidenced by the high mortality rate, which ranks first among gynecological tumors. Therefore, there is an urgent need to develop new and effective treatment strategies. Recent evidence has shown that metabolic processes and cell behaviors in ovarian cancer are regulated by intracellular factors as well as metabolites in the tumor microenvironment (TME), which determine occurrence, proliferation, and metastasis. In this review, we describe the comprehensive landscape of metabolic cross-talk between ovarian cancer and its TME with a focus on the following four aspects: (1) intracellular metabolism based on the Warburg effect, (2) metabolism in non-tumor cells in the ovarian TME, (3) metabolic communication between tumor cells and non-tumor cells in the TME, and (4) metabolism-related therapeutic targets and agents for ovarian cancer. The metabolic cross-talk between ovarian cancer and its microenvironment involves a complex network of interactions, and interrupting these interactions by metabolic interventions is a promising therapeutic strategy.

Tunnel versus medial approach in laparoscopic radical right hemicolectomy for right colon cancer: a retrospective cohort study.

PURPOSE: This study aimed to explore the feasibility and safety of the tunnel approach in laparoscopic radical right hemicolectomy for colon cancer. METHODS: From July 2016 to October 2018, a total of 106 consecutive patients with colon cancer who underwent laparoscopic radical right hemicolectomy at the Affiliated Cancer Hospital of Zhengzhou University were enrolled. The patients were stratified into either a tunnel approach (TA) (n = 56) group or traditional medial approach (MA) (n = 50) group according to the surgical technique performed. The baseline demographics, perioperative outcomes and oncologic outcomes were compared between the two groups. RESULTS: The baseline characteristics did not differ between groups. The TA group had significantly less blood loss [20.0 (10.0-40.0) vs. 100 (100.0-150.0) ml, p < 0.001] and a shorter operation time [128.4 ± 16.7 vs. 145.6 ± 20.3 min, p < 0.001] than the MA group. The time to first flatus and postoperative hospital stay were similar [3.0 (2.0-4.0) vs. 3.0 (3-4.0) days, p = 0.329; 10.4 ± 2.6 vs. 10.7 ± 3.0 days, p = 0.506] between the two groups. The conversion to laparotomy and complication rates were similar between groups (0 vs. 6.0%, p = 0.203; 14.3% vs. 18.0%, p = 0.603, respectively). No treatment-related deaths occurred in either group. The TA group did not have significantly better survival outcomes than the MA group (p = 0.372). CONCLUSIONS: The TA seems to allow for more favourable results in terms of blood loss and operative time than the MA, with similar results regarding time to first flatus, hospital stay, postoperative complication rate, conversion rate and oncologic outcomes; moreover, the TA is easier for beginners to master.

A risk signature with inflammatory and immune cells infiltration predicts survival and efficiency of chemotherapy in gastric cancer.

OBJECTIVE: Tumor immune microenvironment biomarkers might add predictive value for outcomes. This study aimed to construct a risk signature with tumor infiltration immune and inflammatory cells to improve the prediction of survival. METHODS: A risk signature model in combination with CD66b + neutrophils, CD3+ T, CD8+ T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013. RESULTS: The high CD66b expression predicted the poor disease special survival (DSS) and inversely correlated with the CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort. This was comparable to the disease-free survival (DFS) findings observed in the validation cohort. Furthermore, a risk stratification was developed from the integration of CD66b + neutrophils and T immune cells. For DFS and DSS, both demonstrated the worse prognosis in the high-risk group, when compared to the low-risk group in both the training cohort and validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses, and this risk signature model increased the predictive accuracy and efficiency for post-operative relapses. Moreover, the high-risk group identified a subgroup of GC patients who tended not to benefit from the adjuvant chemotherapy. CONCLUSIONS: The incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC and this risk stratification has potential for identifying the subgroup of GC patients who could benefit from adjuvant chemotherapy.