Evaluation of pathologic response and surgical safety of total neoadjuvant therapy for patients with clinical stage III gastric cancer in a real-world setting.

BACKGROUND: Perioperative chemotherapy is the standard treatment for locally advanced gastric cancer. However, the potential benefit of extending therapy before surgery remains largely unknown. In this study, we aimed to evaluate the efficacy and safety of total neoadjuvant chemotherapy, with or without immune checkpoint blockade. METHODS: A cohort of 174 patients with clinical stage III gastric cancer who underwent D2 gastrectomy from October 2021 to March 2024 in the real-world setting were included in this study. Among these patients, 101 were treated with total neoadjuvant therapy (TNT) and 73 were treated with perioperative neoadjuvant therapy (PNT). We compared the pathologic complete response (pCR) rate, ypN0 rate, recurrence-free survival (RFS), overall survival (OS), and postoperative complications between the 2 groups. Multivariate logistic regression analysis was conducted to identify factors associated with pCR or ypN0. RESULTS: Compared with the PNT group, the patients in the TNT group were more frequently treated with intensive chemotherapy with triplets + immunotherapy. Apart from this, there were no significant differences in baseline characteristics. There were no statistically significant differences in pCR (16.8% vs 12.3%), ypN0 (49.5% vs 38.4%), RFS, OS, and postoperative complications (27.7% vs 26.0%) between the TNT and PNT groups. Older age, diffuse type, and stable disease/progressive disease based on clinical efficacy evaluation were independently associated with non-pCR. Stable disease/progressive disease, linitis plastica, and poor differentiation were independently associated with ypN+. Neither the number of neoadjuvant therapy cycles nor the specific regimens were associated with pCR or ypN0. In the subgroup analysis of patients receiving total gastrectomy, there were still no statistically significant differences in pCR (16.7% vs 2.6%), ypN0 (43.8% vs 39.5%), and postoperative complications (45.8% vs 36.8%) between the 2 groups. CONCLUSION: Although TNT did not increase the postoperative complication rate, it also did not provide any additional short-term benefits compared with PNT for clinical stage III gastric cancer.

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy.

BACKGROUND: The prognostic nutritional index (PNI), a marker of immune-nutrition balance, has predictive value for the survival and prognosis of patients with various cancers. AIM: To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December 2020. All patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve analysis. We compared disease-free survival (DFS) and overall survival (OS) between these groups and assessed prognostic factors through univariate and multivariate analyses. RESULTS: The optimal cutoff value for the PNI was established at 45.3. Patients with a PNI ≥ 45.3 were categorized into the PNI-high group, while those with a PNI < 45.3 were assigned to the PNI-low group. Patients within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high group. The 5-year OS rates for patients with a PNI ≥ 45.3 and a PNI < 45.3 were 61.8% and 43.4%, respectively, while the 5-year DFS rates were 53.5% and 38.3%, respectively. Patients in the PNI- low group had shorter OS (P = 0.006) and DFS (P = 0.012). In addition, multivariate analysis revealed that the PNI, pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and DFS. CONCLUSION: The PNI is a straightforward and valuable marker for predicting long-term survival after pancreatoduodenectomy. The PNI should be incorporated into the standard assessment of patients with AC.

Blood transfusion might not be recommended for gastric cancer patients with pretransfusion minimum hemoglobin values higher than 90 g/L: a real-world study covering 20 years of 13470 patients.

BACKGROUND: There was no consistent evidence whether perioperative blood transfusion (PBT) affects the long-term survival of gastric cancer (GC) patients after undergoing gastrectomy. This study aimed to investigate the effects of PBT on long-term survival of GC patients, as well as to determine the threshold of PBT and provide evidence for future surgical practice. METHODS: We performed this real-world study of GC patients undergoing gastrectomy in China National Cancer Center from January 1, 2000 to December 30, 2019. Overall survival (OS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the risk factors for OS. RESULTS: In total, 13470 GC patients undergoing gastrectomy from 2000 to 2019 was included, of whom 3465 (34.6%) GC patients received PBT. PBT ratios declined from 29.1% (114/392) in 2000 to 11.2% in 2019 (149/1178), with the highest blood transfusion ratio in 2005 at 43.7% (220/504). For patients transfused with red blood cells, the median value of hemoglobin (Hb) before transfusion in the PBT group decreased from 110 g/L in 2000 to 87 g/L in 2019. Compared with patients who not receiving perioperative blood transfusion (NPBT), PBT group are more likely to be older (≥65, 39.1% vs. 30.1%, P<0.001), open operation (89.7% vs. 78.1%, P<0.001), higher ASA score (>2, 25.3% vs. 14.9%, P<0.001) and in the later pTNM stage (pTNM stage III, 68.5% vs. 51.5%, P<0.001). Results of multivariable Cox regression analysis showed that PBT was an independent prognostic factor for worse OS in GC patients undergoing gastrectomy (HR=1.106, 95% CI, 1.01-1.211, P=0.03). After stratified according to tumor stage, we found that PBT group had a worse prognosis only in pTNM stage III (HR=1.197, 95% CI, 1.119-1.281, P<0.001). OS was obviously poor in the PBT group when Hb levels were higher than 90 g/L (90 g/L120 g/L:HR= 1.207, 95% CI, 1.098-1.327, P<0.001), while there was no difference between the two groups when Hb levels were lower than or equal to 90 g/L (Hb≤90 g/L: HR=1.162, 95% CI, 0.985-1.370, P=0.075). CONCLUSION: In conclusion, PBT was an independent prognostic factor for worse OS. Blood transfusion might not be recommended for gastric cancer patients with perioperative minimum Hb values higher than 90 g/L.

Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of Disease Study 2019: a cross-sectional study.

BACKGROUND: Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. AIM: To systematically investigate the burden and trend of EOPC based on global populations. METHODS: In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100 000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. RESULTS: According to the GBD 2019 estimates, there were 36 852 new cases of EOPC and 32 004 related deaths. East Asia had the highest number of cases, with 11 401 incidences and 10 149 deaths. The ASRs were 0.94 per 100 000 individuals for incidence and 0.81 per 100 000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100 000

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

Concurrent clinical and pathological response predicts favorable prognosis of patients with gastric cancer after neoadjuvant therapy: a real-world study.

BACKGROUND: Response of locally advanced gastric cancer (LAGC) to neoadjuvant therapy (NAT) may be associated with prognosis, but which of the clinical or pathological evaluation can accurately predict a favorable prognosis is still controversial. This study aims to compare the effect of clinical and pathological response on the prognosis of patients with gastric cancer. METHODS: This study retrospectively analyzed LAGC patients who underwent NAT followed by surgery in the China National Cancer Center from January 2004 to January 2021. Clinical and pathological responses after NAT were evaluated using RECIST 1.1 and Mandard tumor regression grade system (TRG) respectively. Complete response (CR) and partial response (PR) assessed by computed tomography were regarded as clinical response. For histopathology regression assessment, response was defined as Mandard 1, 2, 3 and non-response as Mandard 4, 5. Furthermore, we combined clinical and pathological evaluation results into a variable termed "comprehensive assessment" and divided it into four groups based on the presence or absence of response (concurrent response, only clinical response, only pathological response, both non-response). The association between the prognosis and clinicopathological factors was assessed in univariate and multivariate Cox regression analysis. RESULTS: In total, 238 of 1073 patients were included in the study after screening. The postoperative pathological response rate and clinical response rate were 50.84% (121/238) and 39.92% (95/238), respectively. 154 patients got consistent results in clinical and pathological evaluation (66 were concurrent response and 88 were both non-response), while the other 84 patients did not. The kappa value was 0.297(p < 0.001), which showed poor consistency. Multivariate Cox regression analysis revealed that comprehensive assessment (P = 0.03), clinical N stage(P < 0.001), vascular or lymphatic invasion (VOLI) (HR 2.745, P < 0.001), and pre-CA724(HR 1.577, P = 0.047) were independent factors for overall survival in patients with gastric cancer. Among four groups in the comprehensive assessment, concurrent response had significantly better survival (median OS: 103.5 months) than the other groups (P = 0.008). CONCLUSION: Concurrent clinical and pathological response might predict a favorable prognosis of patients with gastric cancer after neoadjuvant therapy, further validation is needed in prospective clinical trials with larger samples.

Equivalent Survival between Gastric Large-Cell Neuroendocrine Carcinoma and Gastric Small-Cell Neuroendocrine Carcinoma.

BACKGROUND: According to the 2019 World Health Organization (WHO) classification of gastric neuroendocrine neoplasms, gastric neuroendocrine carcinoma (GNEC) can be further divided into gastric large-cell neuroendocrine carcinoma (GLNEC) and gastric small-cell neuroendocrine carcinoma (GSNEC). Whether the prognoses of the two types have a discrepancy has long been disputed. METHOD: We collected patients diagnosed with GLNEC or GSNEC in the National Cancer Center of China between January 2000 and December 2020. The characteristics and survival outcomes were compared between the two groups. We further verified our conclusion using the SEER dataset. RESULTS: A total of 114 GNEC patients, including 82 patients with GLNEC and 32 patients with GSNEC, have completed treatment in our hospital. Clinicopathologic differences were not observed between patients with GSNEC and GLNEC concerning the sex, age, body mass index, Charlson Comorbidity Index, tumor location, tumor size, stage, treatment received, the expression of neuroendocrine markers (CD56, Chromogranin A, synaptophysin), and score on the Ki-67 index. The 1-year, 3-year, and 5-year overall survival rates of GLNEC and GSNEC were 89.0%, 60.5%, and 52.4%, and 93.8%, 56.3%, and 52.7%, which showed no statistically significant differences. This result was confirmed further by using the SEER dataset after the inverse probability of treatment weighting. CONCLUSIONS: Although with different cell morphology, the comparison of prognosis between the GLNEC and GSNEC has no significant statistical difference.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Dissimilar survival and clinicopathological characteristics of mucinous adenocarcinoma located in pancreatic head and body/tail.

BACKGROUND: Growing evidence shows that pancreatic tumors in different anatomical locations have different characteristics, which have a significant impact on prognosis. However, no study has reported the differences between pancreatic mucinous adenocarcinoma (PMAC) in the head vs the body/tail of the pancreas. AIM: To investigate the differences in survival and clinicopathological characteristics between PMAC in the head and body/tail of pancreas. METHODS: A total of 2058 PMAC patients from the Surveillance, Epidemiology, and End Results database diagnosed between 1992 and 2017 were retrospectively reviewed. We divided the patients who met the inclusion criteria into pancreatic head group (PHG) and pancreatic body/tail group (PBTG). The relationship between two groups and risk of invasive factors was identified using logistic regression analysis. Kaplan-Meier analysis and Cox regression analysis were conducted to compare the overall survival (OS) and cancer-specific survival (CSS) of two patient groups. RESULTS: In total, 271 PMAC patients were included in the study. The 1-year, 3-year, and 5-year OS rates of these patients were 51.6%, 23.5%, and 13.6%, respectively. The 1-year, 3-year, and 5-year CSS rates were 53.2%, 26.2%, and 17.4%, respectively. The median OS of PHG patients was longer than that of PBTG patients (18 vs 7.5 mo, P < 0.001). Compared to PHG patients, PBTG patients had a greater risk of metastases [odds ratio (OR) = 2.747, 95% confidence interval (CI): 1.628-4.636, P < 0.001] and higher staging (OR = 3.204, 95% CI: 1.895-5.415, P < 0.001). Survival analysis revealed that age < 65 years, male sex, low grade (G1-G2), low stage, systemic therapy, and PMAC located at the pancreatic head led to longer OS and CSS (all P < 0.05). The location of PMAC was an independent prognostic factor for CSS [hazard ratio (HR) = 0.7, 95%CI: 0.52-0.94, P = 0.017]. Further analysis demonstrated that OS and CSS of PHG were significantly better than PBTG in advanced stage (stage III-IV). CONCLUSION: Compared to the pancreatic body/tail, PMAC located in the pancreatic head has better survival and favorable clinicopathological characteristics.

Laparoscopic endoscopic cooperative surgery for the duodenal neuroendocrine tumor: a single-center case series (How I Do It).

BACKGROUND: Duodenal neuroendocrine tumors (D-NETs) are uncommon. The surgical treatment for D-NETs was in debate. Laparoscopic and endoscopic cooperative surgery (LECS) is a promising approach for treating gastrointestinal tumors. The study aimed to evaluate the feasibility and safety of LECS for D-NETs. Meanwhile, the authors described the details of the LECS technique. METHODS: All patients diagnosed with D-NETs underwent LECS between September 2018 and April 2022 were retrospectively reviewed. The endoscopic procedures were performed with endoscopic full-thickness resection. The defect was manually closed under the surveillance of the laparoscopy. RESULTS: A total of seven patients were enrolled, including three men and four women. The median age was 58 years (ranging from 39-65). Four tumors were located in the bulb and three in the second portion. All cases were diagnosed as NET with grade G1. The tumor depth was pT1 in two cases and pT2 in five cases. The median specimen size and the tumor size were 22 mm (ranging from 10-30) and 8.0 mm (ranging from 2.3-13.0), respectively. En-bloc resection and curative resection rates are 100 and 85.7%, respectively. There were no severe complications. Until 1 June 2022, there was no recurrence. The median follow-up was 9.5 months (range, 1.4-45.1). CONCLUSIONS: LECS with endoscopic full-thickness resection is a reliable surgical procedure. The minimally invasive advantages of LECS enable more individualized treatment options for a specific group. Limited by the length of observation, the long-term performance of LECS for D-NETs requires additional investigation.

Exploration of the lymphadenectomy strategy for elderly pancreatic ductal adenocarcinoma patients undergoing curative-intent resection.

There has been a long-standing controversy regarding the number of lymph nodes (LNs) examined intraoperatively for accurate lymphatic staging and significantly better survival of patients with pancreatic ductal adenocarcinoma (PDAC), and no consensus has been reached for the elderly with the age of over 75 years. Given these, the present study aims to investigate the appropriate number of examined lymph nodes (ELNs) for elderly patients mentioned above. In this study, population-based data on 20,125 patients in 2000 to 2019 from the Surveillance, Epidemiology, and End Results database were reviewed retrospectively. The eighth edition staging system of the American Joint Committee on Cancer (AJCC) was applied. Propensity score matching (PSM) was performed to reduce the effects of multiple biases. By using binomial probability law and maximally selected rank statistics, the minimum number of ELN (MNELN) for accurate nodal involvement assessment and optimal ELN number for significantly better survival were calculated, respectively. In addition, Kaplan-Meier curves and Cox proportional hazard regression models were constructed for further survival analysis. As a result, 6623 patients were enrolled in total in the study. Elderly patients had fewer lymph node metastases and a smaller lymph node ratio (LNR) (all P<0.05). However, poorer overall survival (OS) and cancer-specific survival (CSS) of elderly patients were observed in each pN stage (all P<0.05), except for CSS in N2. The proportions of N2 and N0 stages increased and decreased respectively with increasing number of ELN significantly. MNELN for accurate nodal assessment was 19 according to binomial probability law, and the optimal ELN number for significantly better survival was 17. Additionally, the number of ELN (<17 or ≥17) was also considered a strong prognostic predictor for elderly PDAC patients (≥75 years) in the Cox proportional hazard regression model (Overall survival: hazard ratio [HR]=0.74, 95% confidence interval [CI]: 0.65-0.83, P<0.001; Cancer-specific survival: HR=0.75, 95% CI: 0.66-0.85, P<0.001). In conclusion, extended lymphadenectomy is suitable for elderly PDAC patients undergoing curative-intent surgery owing to an accurate assessment of nodal status and improved long-term prognosis. However, a random, prospective clinical trial is warranted before the recommendation of extended lymphadenectomy for the elderly.

CD93 serves as a potential biomarker of gastric cancer and correlates with the tumor microenvironment.

BACKGROUND: The tumor microenvironment (TME) plays an important role in the growth and expansion of gastric cancer (GC). Studies have identified that CD93 is involved in abnormal tumor angiogenesis, which may be related to the regulation of the TME. AIM: To determine the role of CD93 in GC. METHODS: Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas. Additionally, RNA-seq data sets from Gene Expression Omnibus (GSE118916, GSE52138, GSE79973, GSE19826, and GSE84433) were applied to validate the results. We performed the immune infiltration analyses using ESTIMATE, CIBERSORT, and ssGSEA. Furthermore, weighted gene co-expression network analysis (WGCNA) was conducted to identify the immune-related genes. RESULTS: Compared to normal tissues, CD93 significantly enriched in tumor tissues (t = 4.669, 95%CI: 0.342-0.863, P < 0.001). Higher expression of CD93 was significantly associated with shorter overall survival (hazard ratio = 1.62, 95%CI: 1.09-2.4, P = 0.017), less proportion of CD8 T and activated natural killer cells in the TME (P < 0.05), and lower tumor mutation burden (t = 4.131, 95%CI: 0.721-0.256, P < 0.001). Genes co-expressed with CD93 were mainly enriched in angiogenesis. Moreover, 11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA. CONCLUSION: CD93 is a novel prognostic and diagnostic biomarker for GC, that is closely related to the immune infiltration in the TME. Although this retrospective study was a comprehensive analysis, the prospective cohort studies are preferred to further confirm these conclusions.

At least 16 lymph nodes are recommended to examine during pancreaticoduodenectomy in ampullary adenocarcinoma.

The minimum number of lymph nodes to be examined during pancreaticoduodenectomy (PD) for patients with ampullary adenocarcinoma (AC) is still debatable due to limited clinical data. Therefore, here we explored the relationship between the number of examined lymph node (ELN) and the current N staging (American Joint Committee on Cancer staging system, AJCC, 8 edition) after PD for AC as well as determined the minimum number of examined lymph nodes (MNELN) to ensure the accurate detection of nodal involvement. Patients underwent PD for AC in the National Cancer Center cohort of China (NCC cohort of China) from 1998 to 2020 and in the Surveillance, Epidemiology, and End Results database (SEER database) from 2010 to 2018 were retrospectively reviewed, and a total of 452 eligible patients were included in this study. The MNELN was evaluated by binomial probability law and best survival separation methods. Furthermore, the cut-off value of MNELN was validated in the NCC cohort of China using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Our analysis indicated that the median number of ELN was 14, and the number of ELN was positively correlated with N stage. The MNELN was 16, whereas the best survival separation of ELN was 38 in node-positive patients and 3 in node-negative patients. In the validation cohort, the number of 16 ELNs was identified as a predictive variable for lymph node metastasis with nonzero coefficients in the LASSO-logistic regression model. Together, we concluded that a greater number of ELN was associated with more accurate nodal status assessment in PD for AC patients. A minimum of 16 lymph nodes were required to during PD in AC patients.

Does Surgical Resection Significantly Prolong the Long-Term Survival of Patients with Oligometastatic Pancreatic Ductal Adenocarcinoma? A Cross-Sectional Study Based on 18 Registries.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a type of lethal gastrointestinal malignancy. It is mainly discovered at, and diagnosed with, an advanced stage of metastasis. As the only potentially curative treatment for PDAC, surgical resection has an uncertain impact on the survival of these patients. As such, we aimed to investigate if patients with metastatic PDAC (mPDAC) benefit from surgery. Methods: Patients with pancreatic cancer in 18 registries of the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were reviewed retrospectively. According to the American Joint Committee on Cancer (AJCC), the eighth edition staging system was utilized. Propensity score matching was applied to strengthen the comparability of the study. The impact of surgery on survival was evaluated by restricted mean survival time (RMST) and Kaplan−Meier analysis. Results: A total of 210 well-matched mPDAC patients were included in the study. The 1 year, 3 year, and 5 year overall survival (OS) of patients undergoing surgery was 34.3%, 15.2%, and 11.0%, respectively. The 1 year, 3 year, and 5 year cancer-specific survival (CSS) of these patients was 36.1%, 19.7%, and 14.2%, respectively. RMST analysis revealed that mPDAC patients with surgery had better OS and CSS than those without (OS: 9.49 months vs. 6.45 months, p < 0.01; CSS: 9.76 months vs. 6.54 months, p < 0.01). Nevertheless, subgroup analysis demonstrated that such statistical significance especially existed in oligometastatic PDAC patients, which refers to those metastases that were limited in number and concentrated to a single organ in this study. Additionally, surgery was identified as a significant predictor for the long-term prognosis of patients (OS: [HR, hazard ratio] = 0.48, 95% CI: 0.36−0.65, p < 0.001; CSS: HR = 0.45, 95% CI: 0.33−0.63, p < 0.001). Lastly, a nomogram was established to predict whether an individual was suitable for surgical treatment in this study. Conclusions: Surgical resection significantly prolonged the long-term prognosis of oligometastatic PDAC patients. Such insights might broaden the management of patients with mPDAC to a large extent. However, a prospective clinical trial should be conducted before a recommendation of surgery in these patients.

Prognostic and Immunological Significance of Rhomboid Domain Containing Protein 1 in Multiple Primary Cancers.

BACKGROUND: RHBDD1 is an intramembrane serine protease of the rhomboid superfamily that regulates diverse physiological and pathological processes. However, the relationship between RHBDD1 expression, tumor-infiltrating immune cells (TIICs), and cancer prognosis remains unclear. OBJECTIVE: We comprehensively analyzed the prognostic and immunological significance of RHBDD1 in multiple primary cancers. METHODS: RHBDD1 expression was investigated using Oncomine, TIMER, and UALCAN databases, after which the clinical prognostic value of RHBDD1 was assessed with online public databases. In addition, we explored the correlation between RHBDD1 and TIICs by TIMER and GEPIA and investigated the relationship between RHBDD1 expression and chemokines in cancers by TIMER. RESULTS: In general, compared to that in adjacent normal tissue, lower expression of RHBDD1 was found in various cancers and was correlated to pathological stages. Although RHBDD1 showed a protective effect on multiple solid tumors, a high expression level of RHBDD1 was detrimental to the survival of stomach adenocarcinoma patients. RHBDD1 was positively correlated to immune infiltration levels in various cancers, including lung, breast, ovarian, and gastric cancer. Furthermore, gene markers of TIICs, such as tumor-associated macrophages (TAMs), dendritic cells (DCs), and regulatory T cells, were also correlated to RHBDD1 expression. In addition, the RHBDD1 expression level was positively correlated to multiple chemokines in cancers, which could recruit diverse immune cells at the tumor site. CONCLUSIONS: RHBDD1, which correlates with immune infiltration, can be used as a potential prognostic biomarker in multiple primary cancers. Specifically, RHBDD1 expression potentially contributes to the recruitment of TAMs and DCs and the regulation of T cell functions in cancers.

Effects of Serum Lipids on the Long-Term Prognosis of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy.

BACKGROUND: Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. METHODS: Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p < 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21-0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. CONCLUSIONS: High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion.

Impact of Diabetes on Short-Term and Long-Term Outcomes of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy.

BACKGROUND: Many studies have confirmed that diabetes was associated with prognosis in many malignant cancer types. However, the impact of diabetes on ampullary carcinoma (AC) has not been investigated. METHODS: A total of 266 AC patients in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. The postoperative complication rate, postoperative recurrence rate, and long-term survival were compared between the diabetes group and the no diabetes group. RESULTS: A total of 32 AC patients (12.03%) were diagnosed with diabetes before surgery. In total, 111 patients (41.73%) had one or more postoperative complications, and there was no perioperative death. There was no statistically significant difference regarding postoperative complications between the diabetes group and the no diabetes group. Altogether, 120 patients (45.11%) experienced postoperative recurrence. Multivariate analysis revealed that diabetes was an independent risk factor for the recurrence (OR: 2.384, 95% CI: 1.065-5.336, p = 0.035), OS (HR: 1.597, 95% CI: 1.005-2.537, p = 0.047), and RFS (HR: 1.768, 95% CI: 1.068-2.925, p = 0.027) in AC patients after curative pancreatoduodenectomy. CONCLUSIONS: Diabetes may adversely affect the recurrence of patients with AC after curative pancreaticoduodenectomy, leading to an increased risk of poor prognosis in early-stage patients. Further studies involving a large sample size are needed to validate our results.

Long-term survival and pattern of recurrence in ampullary adenocarcinoma patients after curative Whipple's resection: a retrospective cohort study in the National Cancer Center in China.

Due to the low incidence of ampullary adenocarcinoma (AA), the recurrence patterns, risk factors for recurrence and post-recurrence treatment are still debated. The purpose of this study is to clarify such clinical issues based on the retrospective data at the National Cancer Center in China. Finally, one hundred and eighty-two AA patients after curative Whipple's resection from 1998 to 2019 were retrospectively reviewed. Among them, 27 patients had locoregional recurrence and 61 patients had systemic recurrence. However, no significant difference of clinicopathological features and survival were found between locoregional recurrence and distant metastasis. In the recurrence group, the 1-year, 2-year, and 3-year recurrence-free survival and overall survival were 59.1%, 29.5%, 10.2%, 88.6%, 61.6%, and 37.6%, respectively. AA patients with recurrence have a worse prognosis than those without recurrence, regardless of stage. In addition, we found that advanced T stage and lymphovascular invasion were two independent risk factors for RFS in AA patients after curative Whipple's resection. In conclusion, AA patients with recurrence have a poor prognosis. Advanced T stage and lymphovascular invasion were two independent risk factors for recurrence-free survival in AA patients after curative Whipple's resection. Nevertheless, further studies with larger sample sizes are needed to fully validate.

Resection of the Primary Tumor Improves the Survival of Patients With Stage IV Gastric Neuroendocrine Carcinoma.

Background: The prognostic prolongation effect of surgical resection in the management of gastric neuroendocrine carcinoma (GNEC) with distant metastases was still uncertain. The purpose of this study was to investigate the association of primary tumor resection (PTR) with outcomes in patients with stage IV GNEC. Methods: This retrospective study analyzed patients with distant metastatic GNEC diagnosed between 2000 and 2018 and identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into PTR and non-PTR groups. The stabilized inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method and log-rank test. Cox-regression analyses (uni- and multivariate) were performed to evaluate factors potentially influencing survival. Results: A total of 126 patients with a median follow-up of 79 months were identified. Forty-four patients underwent PTR and 82 patients did not undergo surgery. After the IPTW approach, PTR improved the OS in patients with stage IV GNEC (median OS 12 vs. 6 months, P = 0.010). The 1- and 3-year OS for patients with or without PTR were 43.8% and 34.5%, and 27.9% and 6.5%, respectively. The median CSS was 12 months for patients undergoing PTR and 6 months for those who did not. The 1 and 3-year CSS for patients with or without PTR were 45.1% and 37.0%, and 27.9% and 6.5%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, PTR was recognized as an independent factor for improved survival after the occurrence of distant metastatic disease [OS: hazard ratio (HR) = 0.305; 95% confidence interval (CI): 0.196, 0.475; and CSS: HR = 0.278; 95% CI: 0.171, 0.452]. Conclusion: PTR for stage IV GNEC contributes to a better prognosis compared with non-surgery. This study supported the resection of the primary tumor in patients with distant metastatic GNEC.