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 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.

Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging.

BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents. METHODS: Superparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed. RESULTS: The synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn't change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging. CONCLUSION: These data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.

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.

Development and validation of a simple-to-use nomogram to predict liver metastasis in patients with pancreatic neuroendocrine neoplasms: a large cohort study.

BACKGROUND: Liver metastasis is an important prognostic factor for pancreatic neuroendocrine neoplasms (pNENs), but the relationship between the clinical features of patients with pNEN and liver metastasis remains undetermined. The aim of this study was to establish and validate an easy-to-use nomogram to predict liver-metastasis in patients with pNEN. METHODS: We obtained the clinicopathologic data of 2960 patients with pancreatic neuroendocrine neoplasms from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2016. Univariate and multivariate logistic regression were done to screen out independent influencing factors to establish the nomogram. The calibration plots and the area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of nomogram. Decision curve analysis (DCA) was applied to compare the novel model with the conventional predictive methods. RESULTS: A total of 2960 patients with pancreatic neuroendocrine neoplasms were included in the study. Among these, 1974 patients were assigned to the training group and 986 patients to the validation group. Multivariate logistic regression identified, tumor size, grade, other site metastasis, T stage and N stage as independent risk factors. The calibration plot showed good discriminative ability in the training and validation groups, with C-indexes of 0.850 for the training cohort and 0.846 for the validation cohort. The AUC values were 0.850 (95% CI 0.830-0.869) and 0.839 (95% CI 0.812-0.866), respectively. The nomogram total points (NTP) had the potential to stratify patients into low risk, medium risk and high risk (P < 0.001). Finally, comparing the nomogram with traditional prediction methods, the DCA curve showed that the nomogram had better net benefit. CONCLUSIONS: Our nomogram has a good ability to predict liver metastasis of pancreatic neuroendocrine neoplasms, and it can guide clinicians to provide suitable prevention and treatment measures for patients with medium- and high-risk liver metastasis.

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.

Ultrastructural changes in the pulmonary mechanical barriers in a rat model of severe acute pancreatitis-associated acute lung injury.

This study examined the ultrastructural changes in the pulmonary mechanical barriers in a rat model of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). Animals were randomized into the SAP group (n = 60) and the control group (n = 60). SAP was induced by retrograde injection of 5% taurocholic acid into the biliopancreatic duct. The morphological abnormalities assessed by histology and the lung wet/dry weight ratio and the ultrastructural abnormalities assessed by transmission electron microscope and scanning electron microscope examinations plus lanthanum nitrate tracing were compared between the two groups at 6, 12, and 24 h post-SAP induction (n = 10/group/time point). The SAP group had significantly greater extravascular effusion than the control group at each time point as assessed by the lung wet/dry weight ratio (p < .001). The severity of the tissue damage increased in the lung and pancreas over time in the SAP group (all p < .001). In the SAP group, ultrastructural damages to the endothelial, epithelial, and pleural barriers were apparent and the damages to the endothelial barrier were detected earlier than the other two barriers, suggesting its fundamental role in preventing the further development of SAP-associated ALI. Moreover, the ultrastructural abnormalities were detected earlier than symptoms and morphological changes. The ultrastructural damages in the endothelial, epithelial, and pleural barriers occurred in the early stage of SAP. The endothelial barrier is likely to be the first line to prevent the further development in this rat model of SAP-associated ALI.

Surgery for oligometastasis of pancreatic cancer.

The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

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.

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.

The effect of allogenetic bone marrow-derived mesenchymal stem cell transplantation on lung aquaporin-1 and -5 in a rat model of severe acute pancreatitis.

BACKGROUND/AIMS: We aimed to determine the effect of transplantation on post- ALI (acute lung injury) edema in severe acute pancreatitis (SAP) and the expression levels of aquaporins -1 and -5 (AQP-1 and -5). METHODOLOGY: Sprague-Dawley (SD) rats were randomized into control-SAP and BMSCs-SAP groups. SAP model was prepared through retrograde injection of 5% taurocholic acid. BMSCs were isolated from the bone marrow of SD rats. We examined SAP rats for levels of IL-1ß and TNF-a, and for AQP-1 and -5 expression in lung tissues at 6 and 12 hours. RESULTS: The levels of IL-1ß and TNF-a in BMSC-SAP rats were lower than in control-SAP rats (both, p<0.001). Real-time RT-PCR analysis showed that AQP-1 mRNA expression in BMSC-SAP rats was higher than that in control-SAP rats (p=0.005 and p<0.001), and AQP-5 mRNA expression in BMSC-SAP rats was also higher than that in control-SAP rats (p=0.031 and p=0.006). Western blotting analysis showed that AQP-1 and AQP-5 protein levels at 12h were significantly higher in BMSC-SAP rats than in control-SAP rats (p<0.001). CONCLUSIONS: Allogenic BMSC transplantation can protect against ALI in a rat SAP model and can also regulate the expression levels of AQP-1 and -5 by inhibiting IL-1ß and TNF-a.