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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.

For many solid tumors, immune checkpoint blockade therapy has become first line treatment, yet a large proportion of patients with immunologically cold tumors do not benefit due to the paucity of tumor infiltrating lymphocytes. Here we show that the orphan G Protein-Coupled Receptor 182 (GPR182) contributes to immunotherapy resistance in cancer via scavenging chemokines that are important for lymphocyte recruitment to tumors. GPR182 is primarily upregulated in melanoma-associated lymphatic endothelial cells (LECs) during tumorigenesis, and this atypical chemokine receptor endocytoses chemokines promiscuously. In GPR182-deficient mice, T cell infiltration into transplanted melanomas increases, leading to enhanced effector T cell function and improved antitumor immunity. Ablation of GPR182 leads to increased intratumoral concentrations of multiple chemokines and thereby sensitizes poorly immunogenic tumors to immune checkpoint blockade and adoptive cellular therapies. CXCR3 blockade reverses the improved antitumor immunity and T cell infiltration characteristic of GPR182-deficient mice. Our study thus identifies GPR182 as an upstream regulator of the CXCL9/CXCL10/CXCR3 axis that limits antitumor immunity and as a potential therapeutic target in immunologically cold tumors., Immunologically cold tumours don’t respond to immune checkpoint blockade inhibition due to poor recruitment of anti-tumour T cells. Authors show here that melanoma-associated lymphatic endothelial cells express G Protein-Coupled Receptor 182 that scavenges CXCL9 and other chemokines necessary for T cell recruitment.

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 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.

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.

Summary Background The benefit and safety of laparoscopic pancreatoduodenectomy (LPD) for the treatment of pancreatic or periampullary tumours remain controversial. Studies have shown that the learning curve plays an important role in LPD, yet there are no randomised studies on LPD after the surgeons have surmounted the learning curve. The aim of this trial was to compare the outcomes of open pancreatoduodenectomy (OPD) with those of LPD, when performed by experienced surgeons. Methods In this multicentre, open-label, randomised controlled trial done in 14 Chinese medical centres, we recruited patients aged 18–75 years with a benign, premalignant, or malignant indication for pancreatoduodenectomy. Eligible patients were randomly assigned (1:1) to undergo either LPD or OPD. Randomisation was centralised via a computer-generated system that used a block size of four. The patients and surgeons were unmasked to study group, whereas the data collectors, outcome assessors, and data analysts were masked. LPD and OPD were performed by experienced surgeons who had already done at least 104 LPD operations. The primary outcome was the postoperative length of stay. The criteria for discharge were based on functional recovery, and analyses were done on a modified intention-to-treat basis (ie, including patients who had a pancreatoduodenectomy regardless of whether the operation was the one they were assigned to). This trial is registered with Clinicaltrials.gov , number NCT03138213 . Findings Between May 18, 2018, and Dec 19, 2019, we assessed 762 patients for eligibility, of whom 656 were randomly assigned to either the LPD group (n=328) or the OPD group (n=328). 31 patients in each group were excluded and 80 patients crossed over (33 from LPD to OPD, 47 from OPD to LPD). In the modified intention-to-treat analysis (297 patients in the LPD group and 297 patients in the OPD group), the postoperative length of stay was significantly shorter for patients in the LPD group than for patients in the OPD group (median 15·0 days [95% CI 14·0–16·0] vs 16·0 days [15·0–17·0]; p=0·02). 90-day mortality was similar in both groups (five [2%] of 297 patients in the LPD group vs six [2%] of 297 in the OPD group, risk ratio [RR] 0·83 [95% CI 0·26–2·70]; p=0·76). The incidence rate of serious postoperative morbidities (Clavien-Dindo grade of at least 3) was not significantly different in the two groups (85 [29%] of 297 patients in the LPD group vs 69 [23%] of 297 patients in OPD group, RR 1·23 [95% CI 0·94–1·62]; p=0·13). The comprehensive complication index score was not significantly different between the two groups (median score 8·7 [IQR 0·0–26·2] vs 0·0 [0·0–20·9]; p=0·06). Interpretation In highly experienced hands, LPD is a safe and feasible procedure. It was associated with a shorter length of stay and similar short-term morbidity and mortality rates to OPD. Nonetheless, the clinical benefit of LPD compared with OPD was marginal despite extensive procedural expertise. Future research should focus on identifying the populations that will benefit from LPD. Funding National Natural Science Foundation of China and Tongji Hospital, Huazhong University of Science and Technology, China.

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.

The serum soluble CD163 (sCD163) is elevated in patients with inflammatory disease and several types of cancer. However, the prognostic value of serum sCD163 in pancreatic ductal adenocarcinoma (PDAC) has not yet been investigated. In this study, 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 characteristic (ROC) 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, and serum sCD163 level. Serum sCD163 level of patients with PDAC was significantly higher than patients with benign tumor (P = .002) and health controls (P

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.

Pancreatic cancer (PC) is likely to become the second leading cause of malignancy-associated mortality within the next 10 years and surgery remains the best hope for cure. The introduction of effective neoadjuvant treatment (NAT) has increased the resection rate of PC in the era of contemporary pancreatology. This review summarizes the surgical selection criteria for locally advanced PC (LAPC), by focusing on the commonly used predictors for resectability and better overall survival outcome. Based on the currently available evidence, the role of change in carbohydrate antigen 19-9 (CA 19-9) and patient's tumor response to NAT are critical in surgical candidacy selection. Although, consensus on surgical candidacy selection for LAPC still needs to be made, several data have shown that surgery provides the most optimistic chance of cure for PC. Surgery is, therefore, recommended whenever the benefits of pancreatectomy outweigh surgical complications, and the chance of local or distant metastases in the postoperative setting is low. This review also provided our insight for and experience in selecting surgical candidates by focusing on optimizing the overall survival of LAPC patients. Nevertheless, a collaborative approach to formulating standardized criteria for surgical candidate selection and treatment guidelines for LAPC is a common goal that pancreatologists worldwide should focus on.

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.

The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention.

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.

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 Impairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects the BBB in SAP are still unclear. Methods This study includes in vivo experiments using a SAP rat model and in vitro experiments using an in vitro BBB model consisting of a monolayer of brain microvascular endothelial cells (BMECs). The study groups are divided into the control, SAP (in vivo)/TNF-α (in vitro), IL-10 treatment, IL-10 + signal transducer and activator of transcription 3 (STAT3) inhibitor S3I-201 treatment groups. Pancreatic pathological scores, serum amylase, serum TNF-α levels and BBB permeability by Evan’s blue assay in SAP rat models were evaluated. BMEC apoptosis in SAP rats or induced by TNF-αin vitro was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, separately. Expression levels of claudin-5 and proteins involved in the STAT3 signaling pathway were measured by Western blotting. Location and changes of junctional structure of claudin-5 on BMECs were assessed by immunohistochemistry and immunofluorescence. Results In vivo, IL-10 alleviated the severity of inflammation, attenuated the increased BBB permeability in SAP rat models by reducing BMEC apoptosis via the STAT3 pathway and ameliorated the down-regulation of claudin-5 expression in BMECs; in vitro, IL-10 improved BBB integrity against TNF-α by attenuating BMEC apoptosis via the STAT3 pathway, the impairment of tight junction structure and the down-regulation of claudin-5 expression in BMECs. Conclusions IL-10 improves BBB properties in SAP by attenuating the down-regulation of claudin-5 expression and the impairment of tight junctions and by STAT3 pathway-mediated anti-apoptotic effects on BMECs.

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.

Background Impairment of the blood–brain barrier (BBB) could result in secondary cerebral edema and life-threatening pancreatic encephalopathy in patients with severe acute pancreatitis (SAP). Mesenchymal stem cells (MSCs) have been widely adopted in clinical research because of their pleiotropic functions. The aim of this study was to investigate the impact of MSCs on BBB permeability in SAP and the potential mechanisms driving these effects. Methods Sprague-Dawley rats were randomly assigned to the control, SAP and SAP+MSCs groups. Pancreatic impairment was assessed. The serum levels of amylase, TNF-α and IL-10, expression levels of claudin-5, Bax, Bcl-2 and MMP-9, and the BBB permeability were measured. Endothelial cell apoptosis was evaluated. Results SAP rats showed BBB impairment with increased permeability and secondary cerebral edema, which was confirmed using the Evans blue assay and the calculation of the brain dry/wet ratio. Treatment with MSCs decreased the serum levels of amylase and TNF-α, increased the serum levels of IL-10, attenuated the apoptosis of brain microvascular endothelial cells, upregulated claudin-5 expression and downregulated MMP-9 expression. This treatment attenuated the increased BBB permeability in SAP rats. Conclusions MSCs attenuated the impairment of the BBB and decreased its permeability, producing protective effects in SAP rats. Electronic supplementary material The online version of this article (10.1186/s11658-019-0167-8) contains supplementary material, which is available to authorized users.

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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.