Metabolic difference between patient-derived xenograft model of pancreatic ductal adenocarcinoma and corresponding primary tumor.

BACKGROUND: Patients-derived xenograft (PDX) model have been widely used for tumor biological and pathological studies. However, the metabolic similarity of PDX tumor to the primary cancer (PC) is still unknown. METHODS: In present study, we established PDX model by engrafting primary tumor of pancreatic ductal adenocarcinoma (PDAC), and then compared the tumor metabolomics of PC, the first generation of PDX tumor (PDXG1), and the third generation of PDX tumor (PDXG3) by using 1H NMR spectroscopy. Then, we assessed the differences in response to chemotherapy between PDXG1 and PDXG3 and corresponding metabolomic differences in drug-resistant tumor tissues. To evaluate the metabolomic similarity of PDX to PC, we also compared the metabolomic difference of cell-derived xenograft (CDX) vs. PC and PDX vs. PC. RESULTS: After engraftment, PDXG1 tumor had a low level of lactate, pyruvate, citrate and multiple amino acids (AAs) compared with PC. Metabolite sets enrichment and metabolic pathway analyses implied that glycolysis metabolisms were suppressed in PDXG1 tumor, and tricarboxylic acid cycle (TCA)-associated anaplerosis pathways, such as amino acids metabolisms, were enhanced. Then, after multiple passages of PDX, the altered glycolysis and TCA-associated anaplerosis pathways were partially recovered. Although no significant difference was observed in the response of PDXG1 and PDXG3 to chemotherapy, the difference in glycolysis and amino acids metabolism between PDXG1 and PDXG3 could still be maintained. In addition, the metabolomic difference between PC and CDX models were much larger than that of PDX model and PC, indicating that PDX model still retain more metabolic characteristics of primary tumor which is more suitable for tumor-associated metabolism research. CONCLUSIONS: Compared with primary tumor, PDX models have obvious difference in metabolomic level. These findings can help us design in vivo tumor metabolomics research legitimately and analyze the underlying mechanism of tumor metabolic biology thoughtfully.

Feasibility and efficacy of minimally invasive limited resection for primary duodenal gastrointestinal stromal tumors: a retrospective cohort study.

BACKGROUND: The primary duodenal gastrointestinal stromal tumor (GIST) is a rare type of gastrointestinal tract tumor. Limited resection (LR) has been increasingly performed for duodenal GIST. However, only a few studies reported minimally invasive limited resection (MI-LR) for primary duodenal GIST. METHODS: The clinical data of 33 patients with primary duodenal GIST from December 2014 to February 2024 were retrospectively analyzed including 23 who received MI-LR and 10 who received laparoscopic or robotic pancreaticoduodenectomy (LPD/RPD). RESULTS: A total of 33 patients with primary duodenal GIST were enrolled and retrospectively reviewed. Patients received MI-LR exhibited less OT (280 vs. 388.5min, P=0.004), EBL (100 vs. 450ml, P<0.001), and lower morbidity of postoperative complications (52.2% vs. 100%, P=0.013) than LPD/RPD. Patients received LPD/RPD burdened more aggressive tumors with larger size (P=0.047), higher classification (P<0.001), and more mitotic count/50 HPF(P=0.005) compared with patients received MI-LR. The oncological outcomes were similar in MI-LR group and LPD/RPD group. All the patients underwent MI-LR with no conversion, including 12 cases of LLR and 11 cases of RLR. All of the clinicopathological data of the patients were similar in both groups. The median OT was 280(210-480) min and 257(180-450) min, and the median EBL was 100(20-1000) mL and 100(20-200) mL in the LLR and the RLR group separately. The postoperative complications mainly included DGE (LLR 4 cases, 33.4% and RLR 4 cases, 36.4%), intestinal fistula (LLR 2 cases, 16.7%, and RLR 0 case), gastrointestinal hemorrhage (LLR 0 case and RLR 1 case, 9.1%), and intra-abdominal infection (LLR 3 cases, 25.0% and RLR 1 case, 9.1%). The median postoperative length of hospitalization was 19.5(7-46) days in the LLR group and 19(9-38) days in the RLR group. No anastomotic stenosis, local recurrence or distant metastasis was observed during the follow-up period in the two groups. CONCLUSIONS: Minimally invasive limited resection is an optional treatment for primary duodenal GIST with satisfactory short-term and long-term oncological outcomes.

Metabolic responses to the occurrence and chemotherapy of pancreatic cancer: biomarker identification and prognosis prediction.

As the most malignant tumor, the prognosis of pancreatic cancer is not ideal even in the small number of patients who can undergo radical surgery. As a highly heterogeneous tumor, chemotherapy resistance is a major factor leading to decreased efficacy and postoperative recurrence of pancreatic cancer. In this study, nuclear magnetic resonance (NMR)-based metabolomics was applied to identify serum metabolic characteristics of pancreatic ductal adenocarcinoma (PDAC) and screen the potential biomarkers for its diagnosis. Metabolic changes of patients with different CA19-9 levels during postoperative chemotherapy were also monitored and compared to identify the differential metabolites that may affect the efficacy of chemotherapy. Finally, 19 potential serum biomarkers were screened to serve the diagnosis of PDAC, and significant metabolic differences between the two CA19-9 stratifications of PDAC were involved in energy metabolism, lipid metabolism, amino acid metabolism, and citric acid metabolism. Enrichment analysis of metabolic pathways revealed six shared pathways by PDAC and chemotherapy such as alanine, aspartate and glutamate metabolism, arginine biosynthesis, glutamine and glutamate metabolism, citrate cycle, pyruvate metabolism, and glycogolysis/gluconeogeneis. The similarity between the metabolic characteristics of PDAC and the metabolic responses to chemotherapy provided a reference for clinical prediction of benefits of postoperative chemotherapy in PDAC patients.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

Analysis of long-term outcomes after minimally invasive spleen-preserving distal pancreatectomy under the 'Kimura-first' strategy.

INTRODUCTION: Spleen-preserving distal pancreatectomy (SPDP) can be carried out by the Kimura technique (KT) or Warshaw technique (WT). This study aimed to evaluate the long-term post-operative outcomes of the two minimally invasive SPDP methods under the 'Kimura-first' strategy with a particular focus on the haemodynamic changes in the splenogastric circulation. PATIENTS AND METHODS: The electronic medical records and follow-up data of patients who underwent minimally invasive SPDP in our centre from March 2016 to July 2022 were reviewed. The haemodynamic changes in splenogastric circulation were monitored by post-operative computed tomography (CT) images, and the risks they caused were assessed by long-term follow-up. RESULTS: A total of 112 patients (KT = 93 and WT = 19) were included in the study. The tumour size in the WT group was significantly larger than that in the KT group ( P = 0.02). We also found less blood loss for patients who underwent KT ( P = 0.02). The occurrence of gastric varices was significantly higher in the WT group ( P = 0.022). There was no gastrointestinal bleeding in either group. There were two cases of splenic infarction in the WT group (11.1%), and the incidence was higher than that in the KT group ( P = 0.026). The infarct area gradually decreased during periodic CT examinations and disappeared completely at the last review. The two groups of patients had similar results across the 15 items in three areas of the quality of life questionnaire. CONCLUSIONS: The 'Kimura-first' strategy, in which the WT is used as an alternative to the KT when the splenic vessels cannot be safely preserved, is feasible, and safe for minimally invasive SPDP.

The cellular trajectories of tumor-associated macrophages decipher the heterogeneity of pancreatic cancer.

Emerging evidence indicates that the interactions and dynamic changes among tumor-associated macrophages (TAMs) are pivotal in molding the tumor microenvironment (TME), thereby influencing diverse clinical outcomes. However, the potential clinical ramifications of these evolutionary shifts in tumor-associated macrophages within pancreatic adenocarcinoma (PAAD) remain largely unexamined. Single-cell RNA sequencing (scRNA-seq) data were retrieved from the Tumor Immune Single-cell Hub. The Seurat and Monocle algorithms were employed to elucidate the progression of TAMs, using non-negative matrix factorization (NMF) to determine molecular classifications. Subsequently, the prognosis, biological characteristics, genomic modifications, and immune landscape across various clusters were interpreted. Furthermore, the sensitivity of potential therapeutic drugs between subtypes was predicted. Cellular experiments were conducted to explore the function of the NR1H3 gene in pancreatic cancer. These experiments encompassed gene knockdown, proliferation assessment, clone formation evaluation, transwell examination, and apoptosis analysis. Trajectory gene expression analysis of tumor-associated macrophages identified three disparate clusters, each associated with different clinical outcomes Compared to clusters C1 and C2, cluster C3 is seemingly at a less advanced pathological stage and associates with a relatively favorable prognosis. Further investigation revealed pronounced genetic instability in cluster C2, whereas cluster C3 demonstrated notable genetic stability. Cluster C1, characterized as "immune-hot," exhibits an abundance of immune cells and elevated immune checkpoint expression, suggesting its suitability for immunotherapy. Furthermore, several potential therapeutic agents have been pinpointed, potentially facilitating the clinical application of these insights. Cell assays indicated that NR1H3 knockdown markedly induced apoptosis and suppressed clonogenesis, migration, and proliferation of pancreatic cancer cells in the PTAU-8988 and PANC-1 cell lines. Overall, our study discerned three clusters with unique characteristics, defined by the evolution of TAMs. We propose customized therapeutic strategies for patients within these specific clusters to improve clinical outcomes and optimize clinical management.

The CA125 level postoperative change rule and its prognostic significance in patients with resectable pancreatic cancer.

BACKGROUND: The relationship between postoperative CA125 level changes and early recurrence after curative resection of resectable PDAC is still unclear. METHODS: The electronic medical records and follow-up data of patients with resectable pancreatic cancer were evaluated. Dynamic CA125 detection was used to identify the rules for postoperative CA125 level change and its prognostic value in patients with resectable pancreatic cancer. RESULTS: The study included a total of 118 patients with resectable pancreatic cancer who underwent curative resection. Early postoperative CA125 levels were significantly higher than those before surgery (P < 0.05). It decreased gradually in the group without early recurrence (P < 0.05) but not in the early recurrence group (P>0.05). There was no correlation between early postoperative CA125 levels and early recurrence (P > 0.05). CA125 levels three months after surgery were associated with an increased risk of early recurrence (P = 0.038, 95% CI (1.001-1.025)). The cutoff CA125 level at 3 months after surgery for predicting early recurrence was 22.035. Patients with CA125 levels < 22.035 three months postoperatively had similar DFS and OS, regardless of whether the value was exceeded in the early postoperative period, but these values were significantly better than those of patients with CA125 levels > 22.035 at 3 months postoperatively (p < 0.05). CONCLUSIONS: Patients with different prognoses have different patterns of CA125 level changes. Elevations in CA125 levels > 3 months postoperatively, rather than early postoperative elevation, were associated with a poor prognosis.

Laparoscopic transabdominal preperitoneal repair for female patients with groin hernias.

BACKGROUND: Laparoscopic transabdominal preperitoneal repair (TAPP) was recommended for female patients with groin hernias. Whereas, only a few studies focused on whether and how to preserve the round ligament of the uterus in TAPP. METHODS: Clinical data of 159 female patients with 181 groin hernias who underwent TAPP at a single institution in China from January 2016 to June 2022 were retrospectively reviewed and collected. RESULTS: All the patients underwent the operation smoothly without conversion. Division of the round ligament was performed for 33 hernias. Preservation of the round ligament was adopted for 148 hernias, 51 with the "keyhole" technique, 86 with the "longitudinal incision of peritoneum" method, and 11 with total dissection of the round ligament. The mean operative time was 55.6 ± 8.7 min for unilateral TAPP and 99.1 ± 15.8 min for bilateral TAPP. The mean estimated blood loss was 7.1 ± 4.5 mL. The postoperative complications included 6 (3.3%) cases of seroma, 1 (0.5%) case of hematoma, and 3 (1.6%) cases of mild chronic pain. The incidences of chronic pelvic pain and genital prolapse seemed to be higher in the division group than in the preservation groups (6.1% vs. 0.6% and 3.0% vs. 0%, separately). However, no statistical difference was observed (p > 0.05). CONCLUSIONS: TAPP is feasible and effective for female patients with groin hernias, especially in preserving the round ligament of the uterus.

Observational study of surgical resection in small non-functional pancreatic neuroendocrine tumors: AS SEER-based study.

The potential benefits of surgical resection for small non-functional pancreatic neuroendocrine tumors (NF-PNETs) in terms of survival remain uncertain. This study aimed to evaluate the impact of surgical treatment on patients with NF-PNETs. Using SEER data, we identified 1102 patients from 2004 to 2015 with well and moderately differentiated pancreatic neuroendocrine tumors (PNETs). The associations between continuous variables and receipt of surgery were assessed using Wilcoxon rank-sum tests. Kaplan-Meier survival curves for OS were compared using the log-rank test. We compared outcomes in patients who received surgical resection with those in patients who did not, using a univariable Cox model with inverse probability weighting according to the propensity score and propensity-score matching. Among the cohort of 1102 patients, a majority of 965 individuals (87%) underwent surgical intervention. Upon conducting univariate analysis, we observed that surgical treatment significantly prolonged patients' survival [HR = 0.41, 95% CI [0.26-0.65] P < 0.001]. However, the old [HR = 3.27, 95% CI (2.24-4.76), P 0.001], male gender [HR = 1.82, 95% CI (1.23-2.68), P = 0.003], and moderately well-differentiated factors [HR = 1.71, 95% CI (1.04-2.80), P = 0.034] were found to potentially decrease patients' survival time. In the multivariate analysis, male gender [HR = 1.73, 95% CI (1.15-2.61), P = 0.009] and the old factor [HR = 3.52, 95% CI (2.33-5.31), P < 0.001] emerged as influential predictors with higher hazard ratios. Notably, surgical treatment remained a significant factor associated with improved overall survival [HR = 0.53, 95% CI (0.33-0.84), P = 0.007]. Propensity-score matching and inverse probability weighting were employed as analytical techniques. The univariate analysis results showed favorable outcomes in the weight group [HR = 0.48, 95% CI (0.29-0.78), P = 0.003] and matched group [HR = 0.44, 95% CI (0.22-0.85), P = 0.015], respectively. Survival analysis further confirmed that surgical treatment contributed to increased overall survival (log rank, P < 0.05) in both the matching and weight groups. Patients diagnosed with small, non-functioning pancreatic neuroendocrine tumors who undergo surgical intervention exhibit improved overall survival (OS) outcomes. Therefore, surgery is strongly recommended for this patient population.

Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer.

Introduction: Resistance to gemcitabine is common and critically limits its therapeutic efficacy in pancreatic ductal adenocarcinoma (PDAC). Methods: We constructed 17 patient-derived xenograft (PDX) models from PDAC patient samples and identified the most notable responder to gemcitabine by screening the PDX sets in vivo. To analyze tumor evolution and microenvironmental changes pre- and post-chemotherapy, single-cell RNA sequencing (scRNA-seq) was performed. Results: ScRNA-seq revealed that gemcitabine promoted the expansion of subclones associated with drug resistance and recruited macrophages related to tumor progression and metastasis. We further investigated the particular drug-resistant subclone and established a gemcitabine sensitivity gene panel (GSGP) (SLC46A1, PCSK1N, KRT7, CAV2, and LDHA), dividing PDAC patients into two groups to predict the overall survival (OS) in The Cancer Genome Atlas (TCGA) training dataset. The signature was successfully validated in three independent datasets. We also found that 5-GSGP predicted the sensitivity to gemcitabine in PDAC patients in the TCGA training dataset who were treated with gemcitabine. Discussion and conclusion: Our study provides new insight into the natural selection of tumor cell subclones and remodeling of tumor microenvironment (TME) cells induced by gemcitabine. We revealed a specific drug resistance subclone, and based on the characteristics of this subclone, we constructed a GSGP that can robustly predict gemcitabine sensitivity and prognosis in pancreatic cancer, which provides a theoretical basis for individualized clinical treatment.

High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor response to immune checkpoint inhibitors. The mechanism of such poor response is not completely understood. Methods: We assessed T-cell receptor (TCR) repertoire and RNA expression at the single-cell level using high-dimensional sequencing of peripheral blood immune cells isolated from PDAC patients and from healthy human controls. We validated RNA-sequencing data by performing mass cytometry (CyTOF) and by measuring serum levels of multiple immune checkpoint proteins. Results: We found that proportions of T cells (CD45+CD3+) were decreased in PDAC patients compared to healthy controls, while proportion of myeloid cells was increased. The proportion of cytotoxic CD8+ T cells and the level of cytotoxicity per cell were increased in PDAC patients, with reduced TCR clonal diversity. We also found a significantly enriched S100A9+ monocyte population and an increased level of TIM-3 expression in immune cells of peripheral blood in PDAC patients. In addition, the serum level of soluble TIM-3 (sTIM-3) was significantly higher in PDAC patients compared to the non-PDAC participants and correlated with worse survival in two independent PDAC cohorts. Moreover, sTIM-3 exhibited a valuable role in diagnosis of PDAC, with sensitivity and specificity of about 80% in the training and validation groups, respectively. We further established an integrated model by combining sTIM-3 and carbohydrate antigen 19- 9 (CA19-9), which had an area under the curve of 0.974 and 0.992 in training and validation cohorts, respectively. Conclusion: Our RNA-seq and proteomic results provide valuable insight for understanding the immune cell composition of peripheral blood of patients with PDAC.

A randomized controlled trial evaluating effects of prophylactic irrigation-suction near pancreaticojejunostomy on postoperative pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common complication after pancreaticoduodenectomy (PD). However, whether irrigation-suction (IS) decreases the incidence and severity of CR-POPF has not yet been well elucidated. METHODS: One hundred and twenty patients with planned PD were enrolled in the study at a high-volume pancreatic center in China from August 2018 to January 2020. A randomized controlled trial (RCT) was conducted to evaluate whether irrigation-suction (IS) decreases the incidence and severity of CR-POPF and other postoperative complications after PD. The primary endpoint was the incidence of CR-POPF, and the secondary endpoints were other postoperative complications. RESULTS: Sixty patients were assigned to the control group and 60 patients to the IS group. The IS group had a comparable POPF rate (15.0% vs. 18.3%, p = 0.806) but a lower incidence of intra-abdominal infection (8.3% vs. 25.0%, p = 0.033) than the control group. The incidences of other postoperative complications were comparable in the two groups. The subgroup analysis for patients with intermediate/high risks for POPF also showed an equivalent POPF rate (17.0% vs. 20.4%, p = 0.800) and a significantly decreased incidence of intra-abdominal infection (8.5% vs. 27.8%, p = 0.020) in the IS group than that in the control group. The logistic regression models indicated that POPF was an independent risk factor for intra-abdominal infection (OR 0.049, 95% CI 0.013-0.182, p = 0.000). CONCLUSIONS: Irrigation-suction near pancreaticojejunostomy does not reduce the incidence or severity of postoperative pancreatic fistula but decreases the incidence of intra-abdominal infection after pancreaticoduodenectomy.

Textbook outcome as a composite outcome measure in laparoscopic pancreaticoduodenectomy: a multicenter retrospective cohort study.

BACKGROUND: Textbook outcome (TO) is a composite outcome measure for surgical quality assessment. The aim of this study was to assess TO following laparoscopic pancreaticoduodenectomy (LPD), identify factors independently associated with achieving TO, and analyze hospital variations regarding the TO after case-mix adjustment. METHODS: This multicenter cohort study retrospectively analyzed 1029 consecutive patients undergoing LPD at 16 high-volume pancreatic centers in China from January 2010 to August 2016. The percentage of patients achieving TO was calculated. Preoperative and intraoperative variables were compared between the TO and non-TO groups. Multivariate logistic regression was performed to identify factors independently associated with achieving TO. Hospital variations regarding the TO were analyzed by the observed/expected TO ratio after case-mix adjustment. Differences in expected TO rates between different types of hospitals were analyzed using the one-way analysis of variance test. RESULTS: TO was achieved in 68.9% ( n =709) of 1029 patients undergoing LPD, ranging from 46.4 to 85.0% between different hospitals. Dilated pancreatic duct (>3 mm) was associated with the increased probability of achieving TO [odds ratio (OR): 1.564; P =0.001], whereas advanced age (≥75 years) and concomitant cardiovascular disease were associated with a lower likelihood of achieving TO (OR: 0.545; P =0.037 and OR: 0.614; P =0.006, respectively). The observed/expected TO ratio varied from 0.62 to 1.22 after case-mix adjustment between different hospitals, but no significant hospital variations were observed. Hospital volume, the surgeon's experience with open pancreaticoduodenectomy and minimally invasive surgery, and surpassing the LPD learning curve were significantly correlated with expected TO rates. CONCLUSION: TO was achieved by less than 70% of patients following LPD. Dilated pancreatic ducts, advanced age, and concomitant cardiovascular disease were independently associated with achieving TO. No significant hospital variations were observed after case-mix adjustment.

A high serum creatine kinase (CK)-MB-to-total-CK ratio in patients with pancreatic cancer: a novel application of a traditional marker in predicting malignancy of pancreatic masses?

BACKGROUND: The finding that some benign pancreatic masses mimic the imaging appearance of carcinomas poses a challenge for pancreatic surgeons. Preoperative markers that assist in the diagnosis are critical under this circumstance. Abnormal serum creatine kinase (CK) isozyme levels were reported in cancer patients, and this study aimed to explore the potential value of the CK-MB-to-total-CK ratio (CK ratio) in differentiating pancreatic cancer (PC) from benign masses when combined with carbohydrate antigen 19-9 (CA19-9). METHODS: A total of 190 patients primarily diagnosed with pancreatic masses were retrospectively reviewed and assigned to the PC group and the benign pancreatic mass (BPM) group. Sixty-eight controls were enrolled for comparison. Levels of preoperative parameters, including total serum CK, CK-MB, absolute neutrophil count, absolute lymphocyte count, albumin, and CA19-9, were recorded as well as pathological information. A logistic regression model was established to assess the application value of the combination of CA19-9 and the CK ratio in diagnosis. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the markers. RESULTS: The CK ratio was significantly elevated in the PC group compared with the BPM group (P < 0.001). In the multivariate analysis, a CK ratio greater than 0.220 was a statistically significant variable for predicting malignancy of pancreatic masses (P=0.001). Patients with stage III/IV PC had a higher CK ratio than those with stage I/II PC (P<0.01). Combined detection of CA19-9 and the CK ratio produced an increased Youden index (0.739 vs. 0.815) with improved sensitivity (82.2% vs. 89.8%). CONCLUSIONS: The CK ratio is elevated in patients with pancreatic adenocarcinoma and is an independent factor predicting pancreatic adenocarcinoma. The CK ratio augments the diagnostic capacity of CA19-9 in detecting malignancy.

Effects of intraoperative fixation of residual hernia sac on postoperative seroma in laparoscopic transabdominal preperitoneal inguinal hernia repair: a prospective randomized controlled trial.

The study was aimed to evaluate a prospective randomized controlled trial (RCT) In laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP), whether fixation of the residual sac after transecting the hernia sac can reduce the severity of postoperative seroma. A total of 252 male patients with a primary unilateral indirect inguinal hernia who underwent TAPP from September 2018 to November 2022 were recruited. Patients were randomized to the control group (CG)and the experimental group (EG). In the experimental group, after the hernia sac was transected, the residual sac was fixed to the lower edge of the rectus abdominis, while it was left in the preperitoneal space in the control group. Close follow-up was arranged to observe the incidence of seroma and other postoperative complications. All 214 patients were discharged successfully. 106 patients were randomly assigned to the control group, and 108 patients were assigned to the experimental group. There was no significant difference in the incidence of postoperative fluid extraction between the experimental group and the control group (11.1% VS.10.4%, p = 0.862), but the patients with seroma after the operation had fewer repeated extraction (0% VS. 45.5%, P = 0.033). The incidences of other postoperative complications were comparable in the two groups. In the treatment of indirect inguinal hernia with TAPP, after transecting the hernia sac, suturing and fixing the residual sac to the inferior edge of the rectus abdominis can reduce the incidence of repeated aspiration.

Robotic parenchymal-sparing pancreatectomy and pancreas-sparing duodenectomy avoid pancreaticoduodenectomy for benign and low-grade malignant tumours.

BACKGROUND: Parenchymal-sparing pancreatectomy (PSP) or pancreas-sparing duodenectomy (PSD) is an alternative method for patients with benign or low-grade malignant tumours at the pancreatic head or duodenum. It avoids traumatic pancreaticoduodenectomy (PD) with pancreatic function preservation and improves quality of life. However, few studies have reported on robotic PSP (RPSP) or robotic PSD (RPSD). METHODS: A retrospective analysis of 17 patients with benign and low-grade malignant pancreatic head and duodenal tumours who underwent RPSP or RPSD from January 2018 to February 2022 was conducted. The demographic, perioperative, and postoperative data of all patients were collected and analysed. RESULTS: The operations were successful for all seventeen patients without conversion, including 10 cases of RPSP and 7 cases of RPSD. For RPSP, eight patients underwent pancreatic enucleation, and two patients underwent uncinate process resection. For RPSD, five patients underwent local duodenectomy, and two patients underwent segmental duodenectomy, with five simultaneous jejunostomies and two distal gastrectomies. The median OT and EBL were 135 min and 50 mL for RPSP and 220 min and 100 mL for RPSD, respectively. The median LOS was 8 days for RPSP and 19 days for RPSD. The main postoperative complications for RPSP included POPF (grade B, 6 cases), DGE (grade B, 1 case), PPH (1 case), and intra-abdominal infection (1 case). The main postoperative complications for RPSD included DGE (grade B, 1 case, grade C, 3 cases), postoperative haemorrhage (1 case), intra-abdominal infection (1 case), and duodenal fistula (1 case). One patient underwent interventional drain placement after RPSP because of POPF. CONCLUSION: RPSP or RPSD is feasible for highly selected patients with benign and low-grade malignant pancreatic head and duodenal tumours, avoiding potential pancreaticoduodenectomy.

Transabdominal preperitoneal repair for a recurrent inguinal hernia after Kugel procedure using the medial umbilical ligament: A case report.

The Kugel procedure resulted in extensive adhesion in the preperitoneal space. Performing a transabdominal preperitoneal repair (TAPP) for recurrent hernia after Kugel procedure is extremely difficult. In this case report, we present the case of a 81-year-old male who presented with recurrent inguinal hernia after Kugel procedure 8 years ago. Transabdominal laparoscopy was performed first. Indirect hernia formed inferior to the lateral edge of the previous mesh was diagnosed under laparoscopy. The patient's medial umbilical ligament (MUL) was big enough and could be completely released by separating the Retzius space. Finally, TAPP was successfully performed by using the MUL to create and close the preperitoneal space. No perioperative complications or hernia recurrence was observed 1 year after the surgery. Using the MUL to deal with preperitoneal problems was practical and feasible.

Prognostic value of preoperative enhanced computed tomography as a quantitative imaging biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with high mortality and short survival time. Computed tomography (CT) plays an important role in the diagnosis, staging and treatment of pancreatic tumour. Pancreatic cancer generally shows a low enhancement pattern compared with normal pancreatic tissue. AIM: To analyse whether preoperative enhanced CT could be used to predict postoperative overall survival in patients with PDAC. METHODS: Sixty-seven patients with PDAC undergoing pancreatic resection were enrolled retrospectively. All patients underwent preoperative unenhanced and enhanced CT examination, the CT values of which were measured. The ratio of the preoperative CT value increase from the nonenhancement phase to the portal venous phase between pancreatic tumour and normal pancreatic tissue was calculated. The cut-off value of ratios was obtained by the receiver operating characteristic (ROC) curve of the tumour relative enhancement ratio (TRER), according to which patients were divided into low- and high-enhancement groups. Univariate and multivariate analyses were performed using Cox regression based on TRER grouping. Finally, the correlation between TRER and clinicopathological characteristics was analysed. RESULTS: The area under the curve of the ROC curve was 0.768 (P < 0.05), and the cut-off value of the ROC curve was calculated as 0.7. TRER ≤ 0.7 was defined as the low-enhancement group, and TRER > 0.7 was defined as the high-enhancement group. According to the TRER grouping, the Kaplan-Meier survival curve analysis results showed that the median survival (10.0 mo) with TRER ≤ 0.7 was significantly shorter than that (22.0 mo) with TRER > 0.7 (P < 0.05). In the univariate and multivariate analyses, the prognosis of patients with TRER ≤ 0.7 was significantly worse than that of patients with TRER > 0.7 (P < 0.05). Our results demonstrated that patients in the low TRER group were more likely to have higher American Joint Committee on Cancer stage, tumour stage and lymph node stage (all P < 0.05), and TRER was significantly negatively correlated with tumour size (P < 0.05). CONCLUSION: TRER ≤ 0.7 in patients with PDAC may represent a tumour with higher clinical stage and result in a shorter overall survival.

Metabolomic analyses redefine the biological classification of pancreatic cancer and correlate with clinical outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high heterogeneity, and the postoperative prognosis of different patients often varies greatly. Therefore, the classification of pancreatic cancer patients and precise treatment becomes particularly important. In our study, 1 H NMR spectroscopy was used to analyze the 76 PDAC serum samples and identify the potential metabolic subtypes. The metabolic characteristics of each metabolic subtype were screened out and the relationship between metabolic subtype and the long-term prognosis was further identified. The clinical stages of PDAC did not show the metabolic differences at the serum metabolomic level. And three metabolic subtypes, basic, choline-like and amino acid-enriched types, were defined by the hierarchical cluster analysis of the serum metabolites and the disturbed metabolic pathways. The characteristic metabolites of each PDAC subtype were identified, and the metabolite model was established to distinguish the PDAC patients in the different subtypes. Among the three metabolic subtypes, choline-like type displayed better long-term prognosis compared to the other two types of patients. Metabolic subtypes are of clinical importance and are closer to expressing the heterogeneity in the actual life activities of pancreatic cancer than molecular typing. The excavation of metabolic subtypes based on this will be more in line with clinical reality and more promising to guide clinical precision individualization treatment.

NMR-Based Metabolomics Identify Metabolic Change in Spleen of Idiopathic Thrombocytopenic Purpura Patients.

Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using 1H high-resolution magic angle spinning NMR spectroscopy (1H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825-0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment.