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.

An evidence-based model for predicting conversion to open surgery in minimally invasive distal pancreatectomy.

BACKGROUND: Intraoperative conversion to open surgery is an adverse event during minimally invasive distal pancreatectomy (MIDP), associated with poor postoperative outcomes. The aim of this study was to develop a model capable of predicting conversion in patients undergoing MIDP. METHODS: A total of 352 patients who underwent MIPD were included in this retrospective analysis and randomly assigned to training and validation cohorts. Potential risk factors related to open conversion were identified through a literature review, and data on these factors in our cohort was collected accordingly. In the training cohort, multivariate logistic regression analysis was performed to adjust the impact of confounding factors to identify independent risk factors for model building. The constructed model was evaluated using the receiver operating characteristics curve, decision curve analysis (DCA), and calibration curves. RESULTS: Following an extensive literature review, a total of ten preoperative risk factors were identified, including sex, BMI, albumin, smoker, size of lesion, tumor close to major vessels, type of pancreatic resection, surgical approach, MIDP experience, and suspicion of malignancy. Multivariate analysis revealed that sex, tumor close to major vessels, suspicion of malignancy, type of pancreatic resection (subtotal pancreatectomy or left pancreatectomy), and MIDP experience persisted as significant predictors for conversion to open surgery during MIDP. The constructed model offered superior discrimination ability compared to the existing model (area under the curve, training cohort: 0.921 vs. 0.757, P < 0.001; validation cohort: 0.834 vs. 0.716, P = 0.018). The DCA and the calibration curves revealed the clinical usefulness of the nomogram and a good consistency between the predicted and observed values. CONCLUSION: The evidence-based prediction model developed in this study outperformed the previous model in predicting conversions of MIDP. This model could contribute to decision-making processes surrounding the selection of surgical approaches and facilitate patient counseling on the conversion risk of MIDP.

Whether T-tube biliary drainage is necessary after pancreaticoduodenectomy: a single-center retrospective study.

BACKGROUND: Postoperative complications of pancreaticoduodenectomy (PD) are still a thorny problem. This study aims to verify the preventative impact of T-tube on them. METHODS: The electronic medical records and follow-up data of patients who received pancreaticoduodenectomy in our center from July 2016 to June 2020 were reviewed. According to whether T tube was placed during the operation, the patients were divided into T-tube group and not-T-tube group. Propensity score matching analysis was performed to minimize selection bias. RESULTS: A total of 330 patients underwent PD (Not-T-tube group =226, T-tube group=104). Propensity score matching resulted in 222 patients for further analysis (Not-T-tube group =134, T-tube group=88). Patients' demographics were comparable in the matched cohorts. Significantly higher incidences of clinically relevant postoperative pancreatic fistula (CR-POPF) ((14 (10.45%) VS 20 (22.73%)), P=0.013) were observed in the T-tube group. The total incidence of biliary anastomotic stricture (BAS) was 3.15%. The incidence was slightly lower in the T-tube group, but there was no statistically significant differentiation (6 (4.48%) VS 1 (1.14%), P=0.317). CONCLUSIONS: It is not feasible to prevent postoperative complications with the application of a T-tube in PD.

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.

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 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.

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.

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.

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.

Laparoscopic biopsy and staging for locally advanced pancreatic cancer: experiences of 76 consecutive patients in a single institution.

BACKGROUND: Pathological diagnosis plays a critical role in the treatment of locally advanced pancreatic cancer (LAPC). However, the commonly used biopsy methods still have a number of shortcomings, such as a relatively low diagnostic accuracy and a high incidence of complications. METHODS: A retrospective review was conducted to compare 76 patients with laparoscopic biopsy and staging and 11 patients with CT-guided pancreatic biopsy for LAPC between January 2017 and October 2020. Logistic regression with univariate and multivariate analyses was performed to identify preoperative predictors of occult metastasis. RESULTS: The diagnostic accuracy of laparoscopic biopsy and staging for pancreatic cancer was 100%. Sixty-two patients were confirmed to have LAPC, 59 patients by pancreatic biopsy and three patients by regional lymph node biopsy. Fourteen patients were diagnosed with distant occult metastasis, three patients by liver biopsy and 11 patients by peritoneum biopsy. Nine patients with severe obstructive manifestations underwent a simultaneous bypass procedure. No postoperative hemorrhage, pancreatic fistula, intra-abdominal infection, or trocar site metastasis was observed. Laparoscopic biopsy and staging had a higher diagnostic accuracy (100% vs. 81.8%, p=0.0147) and a shorter duration to chemotherapy (3 days vs. 9 days, p=0.035) than CT-guided biopsy. Elevated CA125 levels (≥35 U/ml) were a significant preoperative predictor of occult metastasis (OR 6.482, 95% CI 1.624-25.874, p=0.008). CONCLUSIONS: Laparoscopic biopsy and staging are safe and effective methods to obtain rapid pathology and precise staging for LAPC patients, especially for patients with elevated CA125 levels.

Surgical Management of Solid Pseudopapillary Neoplasms of Pancreas: A Single-Center Experience of 60 Patients.

BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare neoplasms, and the selection of surgical approaches is still under debate. The aim of this study was to analyze the clinicopathological characteristics and surgical outcomes of SPN patients and to compare the short-term and long-term outcomes between conventional operations and parenchyma-preserving operations. METHODS: Patients who underwent pancreatic resection for SPNs between February 2010 and May 2019 in Fujian Medical University Union Hospital were identified. Clinicopathological details, perioperative data, and long-term follow-up results were retrospectively analyzed. RESULTS: Sixty patients underwent surgical resection for SPNs during the study period: 48 females and 12 males. The mean age was 32.2 years. All patients underwent margin-negative surgical resection. The median follow-up period was 47 months (range: 3~118 months). One patient developed liver metastases 14 months after the operation and received local ablation therapy. All patients were alive during the follow-up. The incidence of postoperative pancreatic fistula was higher in the parenchyma-preserving surgery group than in the conventional surgery group (40.0 vs. 11.1%, p = 0.034). There was no significant difference in the tumor recurrence rate between the 2 groups. Eight (17.7%) and 6 patients (13.3%) in the conventional surgery group demonstrated endocrine and exocrine pancreatic insufficiency, respectively; furthermore, no patients in the parenchyma-preserving surgery group had endocrine or exocrine pancreatic insufficiency, but the incidences were not significantly different between the 2 groups. CONCLUSIONS: Margin-negative surgical resection of SPNs yields a very low rate of tumor recurrence and excellent long-term survival.

Robotic resection for benign primary retroperitoneal tumors via the transperitoneal approach.

BACKGROUND: Surgical resection is the primary treatment for benign primary retroperitoneal tumors. However, only a few studies have reported robotic resection for retroperitoneal tumors due to the low morbidity rate, and only a small fraction of retroperitoneal tumors are eligible for minimally invasive operations. METHODS: A retrospective study enrolling 16 patients with benign primary retroperitoneal tumors between November 2016 and April 2020 was conducted to evaluate the efficacy of robotic resection for benign primary retroperitoneal tumors via the transperitoneal approach. Surgical skills were described in detail and operative experiences were summarized. RESULTS: The operations were uneventfully performed without conversion in all the patients. The median operation time was 135 (120-180) min, and the median estimated blood loss was 25 (20-60) mL. The median duration of diet restoration was 2 (1-2) days and the median length of postoperative hospital stay was 6 (4-7) days. No serious intraoperative or postoperative complications occurred during the perioperative period. CONCLUSIONS: Robotic resection via the transperitoneal approach is a feasible and safe procedure for highly selected patients with benign primary retroperitoneal tumors, with few postoperative complications and a rapid recovery.

Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling.

BACKGROUND: The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. METHODS: By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. RESULTS: An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. CONCLUSION: The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC.

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.

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.

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.