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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).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.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.RPSP or RPSD is feasible for highly selected patients with benign and low-grade malignant pancreatic head and duodenal tumours, avoiding potential pancreaticoduodenectomy.

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.

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.

Resume Introduction Les hernies inguino-scrotales volumineuses (HISV) sont rarement rencontrees et leur traitement est difficile. Le but de cette etude etait d’evaluer l’efficacite de la reparation par voie trans-inguinale preperitoneale (TIPP) avec pose de prothese de Kugel. Methode Une analyse retrospective de 9 patients ayant 11 HISV traitees par voie TIPP de decembre 2008 a janvier 2012, etait faite. Les caracteristiques demographiques, et les donnees perioperatoires etaient recueillies. Resultats Les patients ont une reparation efficace avec omentectomie mais sans resection d’autres organes. La duree operatoire mediane etait de 120 minutes et les pertes sanguines medianes de 75 mL. La surface de perte de substance parietale mediane etait de 72 cm2. Le delai median de reprise de l’alimentation etait de 4 jours et la duree d’hospitalisation mediane de 6 jours. Le drainage preperitoneal etait arrete au bout de 5 jours, et le drainage scrotal au bout de 6 jours. Trois patients ont presente une elevation de la pression intra-abdominale dont un a eu un syndrome des compartiments abdominaux avec insuffisance respiratoire. Aucun hematome, serome, infection, recidive, ou douleur chronique n’etaient observes. Conclusions La reparation des HISV par TIPP avec une prothese de Kugel est faisable et efficace.

BACKGROUND: Uncinate process dissection is a key step in minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic and robotic procedures, which increase the intraoperative blood loss and operative time and decrease the R0 resection rate if improperly handled. However, few studies have reported the operative skills in detail. METHODS: We performed uncinate process dissection using a combination of the anterior superior mesenteric vein (SMV)-first approach and the right posterior superior mesenteric artery (SMA)-first approach in MIPD for 138 patients with periampullary tumors between March 2017 and October 2019. The demographic and perioperative data of all the patients were collected to evaluate the efficacy of this method. RESULTS: All patients underwent an uneventful operation. An assistant incision was performed to separate extensive adhesion between the tumor and the SMV in 3 patients. The combined approach had a notably shorter operation time and resection time, less intraoperative blood loss and a shorter postoperative hospital stay than the traditional approach (P0.05). There were no deaths during the perioperative period. CONCLUSIONS: The combination of the anterior SMV-first approach and the right posterior SMA-first approach is a safe and feasible technique for uncinate process dissection in MIPD.

Background A superior lumbar hernia is a posterior ventral hernia that is rarely encountered in the clinical setting. However, no standard operative strategy exists for superior lumbar hernia repair at present. Methods Twelve patients with primary superior lumbar hernia who underwent sublay repair via the retroperitoneal space with the Kugel patch between December 2008 and June 2019 were included in this study. The demographic, peri‐operative and post‐operative data of the patients were collected to analyse the effectiveness of this technique. Results All patients underwent an uneventful operation. The median operative time was 60 min, and the median blood loss was 35 mL. The median hernia defect area was 16 cm2. Five medium‐sized Kugel patches (11 cm × 14 cm) and seven large‐sized Kugel patches (14 cm × 17 cm) were used for the repairs. The median visual analogue scale score on post‐operative day 1 was 3. The median time to removal of drainage was 3 days. The median duration of the hospital stay was 3 days. No serious post‐operative complications, including seroma, haematoma, incision or mesh infection, recurrence and chronic pain, occurred during the follow‐up period. Conclusion Sublay repair for primary superior lumbar hernia with the Kugel patch shows benefits including a reliable repair, minimal invasiveness and few post‐operative complications., Repair for superior lumbar hernias is technically challenging. Sublay repair using the Kugel mesh is a feasible and effective method for superior lumbar hernias. Sublay repair for superior lumbar hernias provides the advantages of reliable repair and rapid recovery.

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.

Background Robotic pancreaticoduodenectomy (RPD) has been increasingly performed for patients with periampullary tumours and tumours in the pancreatic head. This method offers several technical advantages compared to open and laparoscopic surgeries. However, the surgical results often vary depending on the experience of different pancreatic centres. Methods A retrospective study of our first 55 cases of RPD from August 2016 to April 2020 was conducted to evaluate the perioperative outcomes of RPD and to summarize the operative experiences in a single intuition. Benign and malignant tumours in the pancreatic head or periampullary tumours without obvious vascular and adjacent organ invasion were included in this study. Perioperative characteristics and postoperative complications of the enrolled patients were retrospectively collected. Results The first 17 cases were robot-assisted laparoscopic pancreaticoduodenectomy (RA-LPD) and the remaining 38 patients underwent total RPD. The RA-LPD group had a remarkably longer operative time than the total RPD group (415.3±89.2 vs. 362.4±75.6 min, P=0.047). The incidences of biliary leakage, chyle leakage, DGE, intra-abdominal infection and intra-abdominal haemorrhage were 3.6%, 0.0%, 5.5%, 9.1% and 5.5%, respectively. Two patients underwent relaparotomy due to severe intra-abdominal haemorrhage. The median length of hospital stay was 14 (11 to 19) days. There were no deaths during the perioperative period. Conclusions RPD is a technically feasible procedure for selected patients with periampullary tumours and tumours in the pancreatic head in experienced hands.

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. 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. 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). 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.

Objective V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. Methods Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. Results The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. Conclusion VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.

Background Seroma is a common and inevitable postoperative complication in transabdominal preperitoneal (TAPP) hernia repair, especially in patients with large inguinoscrotal hernias. However, studies have rarely reported drainage in TAPP for large inguinoscrotal hernias. Methods Sixty-five patients with 78 large indirect inguinoscrotal hernias who underwent TAPP procedure with drainage between September 2016 and December 2019 were enrolled in this study. 181 patients with Type Ⅲ indirect inguinal hernias (European Hernia Society (EHS) classification, hernia defect >3 cm) who underwent TAPP without drainage (no-drainage group) between January 2019 and December 2019 were included for a comparison. In the drainage group, a 12-Fr drainage tube was inserted into the distal hernia sac via the preperitoneal space to decrease the incidence of seroma. Results There was no conversion to open procedures in all the patients. The operative time (56.5 ± 8.4 VS 54.8 ± 9.6 min, unilateral; 95.8 ± 10.4 VS 92.1 ± 13.9 min, bilateral), blood loss (5.9 ± 1.9 VS 5.6 ± 1.7 mL), visual analogue scale score on postoperative day 1 (2.3 ± 0.5 VS 2.2 ± 0.5) and postoperative hospital stay (1.1 ± 0.3 VS 1.0 ± 0.2 days) in the drainage group were equivalent to those in the no-drainage group (p > 0.05). The mean length of drainage was 5.2 ± 1.3 days. The drainage group had a significantly lower incidence of seroma than the no-drainage group (1.5% VS 9.4%, p = 0.037). The postoperative complications including haematoma, recurrence and chronic pain were comparable in the two groups. Conclusion Drainage with appropriate duration is a feasible, safe and effective measure to decrease the incidence of seroma in TAPP for patients with large inguinoscrotal hernias.

Radiofrequency ablation (RFA) is an effective local therapy approach for treating solitary tumor of many types of malignancy. The impact of RFA on the tumor immune microenvironment on distant tumors after RFA treatment is still unclear. In this study, by using syngeneic tumor models and single-cell RNA and T-cell receptor sequencing, we have investigated the alterations of tumor-infiltrating immune cells in distant non-RFA tumors. Single-cell RNA sequencing identified six distinct lymphoid clusters, five distinct monocyte/macrophage clusters, three dendritic cells clusters, and one cluster of neutrophils. We found that RFA treatment reduced the proportions of immunosuppressive cells including regulatory T cells, tumor-associated macrophages and tumor-associated neutrophils, whereas increased the percentages of functional T cells in distant non-RFA tumors. Moreover, RFA treatment also altered gene expressions in single-cell level in each cell cluster. By using pseudo-time analysis, we have described the biological processes of tumor-infiltrating CD8+ T cells and monocytes/macrophages based on the transcriptional profiles. In addition, the immune checkpoints including PD-1 and LAG3 were upregulated in the T cells in distant non-RFA tumors after RFA treatment. In conclusion, our data indicate that RFA treatment induced remodeling of tumor immune microenvironment in distant non-RFA tumors in pancreatic cancer mouse model and suggest that combining RFA with immune checkpoint inhibitors may be an effective treatment approach.

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. 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. 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. 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.

Cancer-associated fibroblasts (CAFs) are crucial for forming the desmoplastic stroma that is associated with chemoresistance in pancreatic ductal adenocarcinoma (PDAC). In the clinic, depleting dense stroma in PDAC tumor tissue is a promising chemotherapeutic strategy. In this study, we report that the local hyperthermia can reduce the number of CAFs in the PDAC PDX mouse mode, which further augments chemotherapeutic efficiency in the PDAC therapy. To achieve this goal, a photothermal-chemotherapeutic agent termed as Abraxane@MoSe2 as a vehicle-saving theranostic probe is prepared by simply mixing an FDA-approved Abraxane and hydrophobic MoSe2 nanosheets via electrostatic and hydrophobic interactions. After labeling with indocyanine green (ICG) dye on the Abraxane@MoSe2, a relatively high fluorescence signal (near infrared second (NIR II)) in PDX tumors can be obtained, which can be precisely imaging-guide local photothermal-chemotherapy upon the 808 nm laser irradiation in vivo. Importantly, the synergy therapeutic efficiency in PDAC is enhanced by the photothermal effect reduction of the number of CAFs, which is confirmed viaα-SMA and vimentin immunofluorescence analysis. This combined therapeutic strategy may provide a new sight for PDAC therapy.

// Bohan Zhan 1, * , Shi Wen 2, * , Jie Lu 1 , Guiping Shen 1 , Xianchao Lin 2 , Jianghua Feng 1 and Heguang Huang 2 1 Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China 2 Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China * These authors have contributed equally to this work Correspondance to: Jianghua Feng, email: jianghua.feng@xmu.edu.cn Heguang Huang, email: hhuang2@aliyun.com Keywords: pancreatic ductal adenocarcinoma, xenograft models, nuclear magnetic resonance, metabonomics Received: March 17, 2017 Accepted: April 24, 2017 Published: May 22, 2017 ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for 1 H NMR spectroscopy followed by univariate and multivariate statistical analyses. As results, no obvious metabonomic difference was demonstrated in serum between the two models, however, the model- and cell strain-specific metabonomic differences were observed in tumor tissues. According to the KEGG analysis, ABC transporters, glycerophospholipid metabolism, purine metabolism and central carbon metabolism were identified to be the most significant components involved in metabonomic differences. Considering the methodological discrepancy in SX and OX models, such differences should be contributed to tumor microenvironment. In general, SX are not equivalent to OX models at molecular level. Subcutaneous transplantation displayed its inherent limitations though it offered a simple, inexpensive, reproducible and quantifiable advantage. And orthotopic transplantation may be favorable to simulate PDAC in patients due to its similar pathogenesis to human pancreatic cancer.

Summary Introduction Giant inguinoscrotal hernias are rarely encountered in clinical settings, and their repair is technically challenging. The aim of this study is to evaluate the efficacy of transinguinal preperitoneal repair (TIPP) of giant inguinoscrotal hernias using Kugel mesh. Methods A retrospective analysis was conducted on 9 patients with 11 giant inguinoscrotal hernias who underwent TIPP repair using Kugel mesh between December 2008 and January 2019. Demographics and perioperative and postoperative data were collected, and the operative experience was summarized. Results The patients underwent a successful repair procedure with simultaneous omentectomy but without resection of the other abdominal organs. The median operation time was 120 min, the median intraoperative blood loss was 75 mL and the median defect area was 72 cm2. The median duration for diet restoration was 4 days, and the median postoperative hospital stay was 6 days. The drainage tube placed in the preperitoneal space was removed after a median duration of 5 days, and the drainage tube placed in the distal hernia sac was removed after a median duration of 6 days. Three patients suffered from a postoperative increase in intra-abdominal pressure, while one patient deteriorated into abdominal compartment syndrome accompanied by respiratory dysfunction. No haematomas, seromas, incisional or mesh infections, recurrence or chronic pain occurred during the follow-up period. Conclusions TIPP repair using Kugel mesh is a feasible and effective method for giant inguinoscrotal hernias.

Background Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME. Methods Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline. Results We found that CD47 expression correlated with the level of CD68+ M but not CD163+ M2. High levels of tumor-infiltrating CD68+ M, CD163+ M2, and CD47 expression were significantly associated with worse survival. CD47high/CD68+ Mhigh and CD47high/CD163+ M2high correlated significantly with shorter survival, whereas CD47low/CD68+ Mlow and CD47low/CD163+ M2low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8+ T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1+CD8+ T cells and enhanced expression of key immune activating genes. Conclusion Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.

Background The serum soluble CD163 (sCD163) is elevated in patients with infection disease and several types of cancer. However, the prognostic value of serum sCD163 in pancreatic ductal adenocarcinoma (PDAC) has not yet been investigated. Methods Serum level of sCD163 was measured by using the peripheral blood of 54 patients with PDAC, 20 patients with benign tumor of pancreas, and 30 healthy volunteers (healthy controls). The association between serum sCD163 level and overall survival was analyzed. Receiver operating characteristics (ROCs) curves were generated, and areas under the curve (AUC) were compared to evaluate the diagnostic accuracy, including CA 19-9, CEA, CA 125, CA 153, serum sCD163 level and combination of sCD163 and CA19-9. Results Serum sCD163 level of patients with PDAC was significant higher than patients with benign tumor (p = 0.002) and health controls (p < 0.001). Using ROCs curves, we found that the AUC values of serum sCD163 were higher than those of CA 125 and CA 153, but lower than those of CA 19-9 and CEA. The combination of sCD163 and CA19-9 had higher diagnostic accuracy than CA19-9 or sCD163 alone. In addition, the prognosis of PDAC patients with sCD163 ≥ median was worse than sCD163 < median by using univariate analysis (p = 0.027). Further, multivariate analysis showed that higher level of serum sCD163 was still associated with poorer overall survival (p = 0.030). Serum sCD163 was not associated with tumoral CD163 expression, whereas negatively correlated with lymphocyte to monocyte ratio (r = -0.428, p = 0.001). Conclusion The serum sCD163 has the potential as a new promising parameter to predict the prognosis in PDAC patients.

Additional file 1: Table S1. Clinical and pathologic features of PDAC patients. Table S2. Univariate and multivariate Cox proportional analysis for overall survival. Table S3. Multivariate analysis of CD47 expression combined with PD-L1 expression or TAM in PDAC patients. Analysis was adjusted for diameter, grade, and TNM stage. Figure S1. Tumor-infiltrating CD45+ immune cells in Panc02 tumor-bearing mice for single-cell analysis. Figure S2. Immunostaining of CD4, CD8, iNOS, and CD206 in Panc02 tumors. Figure S3. Heatmap from scRNA-seq displaying expression of select genes in each lymphoid cell subpopulation.

Kugel procedure is a classic preperitoneal herniorrhaphy via the posterior approach for inguinal hernias but it has a steep learning curve. The aim of the study is to evaluate the efficacy of the Kugel procedure via the internal ring approach. Kugel procedures via the internal ring approach were performed on 3673 patients with inguinal hernias between September, 2005 and August, 2017. Demographic data, peri-operative data and postoperative data were collected to evaluate of the efficacy of this technique. None of the patients with inguinal hernias who underwent the Kugel procedure via the internal ring approach was converted to other procedures. The mean operation time for a unilateral hernia was 46.3 ± 15.2 min, with a mean blood loss of 28.9 ± 10.5 mL. The mean visual analogue scale score on postoperative day 1 was 3.1 ± 0.9. Drainage tubes were placed in 266 patients and were removed after a mean duration of 2.8 ± 0.5 days. The mean postoperative hospital stay was 1.2 ± 0.8 days. There were no serious intra-operative complications. Postoperative complications included seroma (n = 84), haematoma (n = 28), ecchymosis (n = 33), superficial incision infection (n = 1), recurrence (n = 1) and mild chronic pain (n = 11). The Kugel procedure via the internal ring approach is a safe, feasible and cost-effective technique for inguinal hernias that retains the benefits of the standard Kugel procedure and is easier to master.

Table S1. The primer sequences used for polymerase chain reaction. Table S2. The nucleotide sequence of the primers used for qRT-PCR. Table S3. The sequence of miR-200c mimic, miR-141 mimic, anti-miR-200c mimic (Has-miR-200c inhibitor), and anti-miR-141 mimic (Has-miR-141 inhibitor) used for lentivirus transfection and luciferase reporter assay. Table S4. Characteristics of patients with pancreatic cancer (N = 37). Table S5. Characteristics of patients with pancreatic cancer from the TCGA database (N = 177). Figure S1. Identifying miR-141/200c target genes using the TargetScan software program. Figure S2. The levels of CpG methylation of the promoter region of miR-200a/200b/429 in PDAC. Figure S3. Lentiviral expression of miR-141 and miR-200c and their inhibitors in pancreatic cancer cell lines. Figure S4. The effect of miR-141 and miR-200c inhibitors on cell migration and invasion in vitro and tumor growth in xenograft. Figure S5. miR-141 and miR-200c inhibit the expression of WIPF1 in HPDE cell line. Figure S6. Lentiviral expression of shWIPF1 in pancreatic cancer cell lines. Figure S7. WIPF1 antagonizes the inhibitory effect of miR-141/200c on cell migration, invasion and metastasis of PDAC. (DOCX 17513 kb)

Pancreatic cancer is a highly malignant disease with a poor prognosis and it is essential to diagnose and treat the disease at an early stage. The aim of this study was to understand the underlying biochemical mechanisms of pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and to identify potential serum biomarkers for early detection of pancreatic cancer. 7,12-Dimethylbenz(a)anthracene (DMBA)-induced PanIN and PDAC rat models were established and the serum samples were collected. The serum samples were measured using (1)H nuclear magnetic resonance (NMR) spectroscopy and analyzed by chemometric methods including principal component analysis (PCA) and (orthogonal) partial least squares discriminant analysis ((O)PLS-DA). The related biochemical pathways were derived from KEGG analysis of the significantly different metabolites. As results, some serum metabolites demonstrated alarming metabolic changes in the precursor lesion of pancreatic cancer (PanIN-2 in this study). These changes involved elevated levels of ketone compounds including 3-hydroxybutyrate, acetoacetate, and acetone, some amino acids including asparagine, glutamate, threonine, and phenylalanine, glycoproteins and lipoproteins including N-acetylglycoprotein, LDL and VLDL, and some metabolites that have been shown to contribute to mutagenicity and cancer promotion such as deoxyguanosine and cytidine. More metabolites were shown to be significantly different between PanIN and PDAC, suggesting that a more complex set of changes occurs from noninvasive precursor lesion to invasive cancer. The serum metabonomic changes of rats with PanIN and PDAC may extend our understanding of pancreatic molecular pathogenesis, and the metabolic variations from PanIN to PDAC will be helpful to understand evolution processes of the pancreatic disease. NMR-based metabonomic analysis of animal models will be beneficial for the human study and will be helpful for the early detection of pancreatic cancer.

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.

In recent years, frequent and severe drought has become a major climate disaster throughout the world, adversely affecting developed and developing regions as well as the environment. Drought can occur in virtually all climate regimes, but it is especially damaging in monsoon, semiarid, and arid regions. The frequency, duration, and spatial extent of drought and the magnitude of agricultural losses and potential environmental effects make it China’s greatest natural disaster. Recent droughts have attracted attention to its impacts and the need for improved assessment and management procedures to help mitigate its adverse effects.