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BackgroundAlthough rapid progress has been achieved in laparoscopic pancreaticoduodenectomy (PD) over the last decade, laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) remains a challenging surgery that has been rarely reported due to not only requiring complicated pancreaticojejunostomy (PJ) but also ensuring sufficient blood supplies to duodenum and common bile duct (CBD). We completed LDPPHR for 22 patients safely and efficiently with innovative techniques.Patients and MethodsClinical outcomes, including rate of conversion to laparotomy, time of residual pancreatic duct reconstruction, incidence of postoperative complications, and time of hospital stay, were collected for 22 consecutive patients who underwent LDPPHR with innovative techniques as follows: application of indocyanine green (ICG) to visualize and preserve CBD and the vessels supplying the duodenum and CBD, Hong’s PJ, and pancreatic duct end-to-end anastomosis (ETEA) for the residual pancreas.ResultsAll surgeries were performed successfully under laparoscopy except for one case. The duration of ETEA was significantly shorter than PJ (18.2 ± 5.1 min versus 27.5 ± 8.3 min, p < 0.05). There was no significant difference in incidence of postoperative complications between the Hong’s PJ and ETEA group. The overall incidence of postoperative pancreatic fistula (POPF) in the Hong’s PJ and ETEA group was 23.5% and 20%, respectively, without grade C fistula. All complications were resolved after conservative treatment.ConclusionsBy utilizing intraoperative ICG navigation, LDPPHR is a minimally invasive, safe, and efficient approach for chronic pancreatitis with pancreatic head stones by using pancreatic duct ETEA and benign or low-grade malignant tumors of the pancreatic head by using Hong’s PJ.

Background Whether elevated homocysteine level is causally associated with small bowel necrosis remains unestablished. We conducted a prospective observational study to analyze the value of serum homocysteine (HCY) in predicting irreversible transmural intestinal necrosis (ITIN) of adhesive small bowel obstruction (ASBO). Methods This prospective observational study was performed between Feb 2023 and Feb 2025 in patients with adhesive small bowel obstruction. The primary outcome was the occurrence of ITIN. The serum levels of different biomarkers in different groups were calculated and compared. Univariable analysis and multivariable analysis were used to assess the association between different biomarkers and ITIN. The Receiver Operating Characteristic Curve (ROC) was used to assess the value for predicting ITIN. Results The patients comprised 129(58.37%) male and 92(41.63%) female with a median age of 70(60–78)(range 18–85 years). Of the 221 patients included, 88(39.82%) received non-operative treatment, and 133(60.18%) underwent surgery. Intestinal resection and ITIN concerned 89(66.92%) and 68(51.13%) of patients who underwent surgery, respectively. Patients underwent surgery had significantly higher serum levels of HCY, ENDOTOXIN, IL-5, IL-6, Hs-CRP, IL-1β, and PCT ( p <0.0001, respectively) than patients receiving non-operative treatment. The levels of the above seven markers ( p <0.05, respectively) in patients with ITIN were significantly higher than in patients with non-necrosis. Univariable analysis and multivariable analysis showed that HCY、ENDOTOXIN and Hs-CRP were independent predictors for small bowel necrosis (odds ratio = 1.420, 1.061 and 1.032; p  = 0 0.000, p  = 0.001 and, p  = 0.019, respectively). The AUC of HCY (0.9253, p <0.0001) was higher compared with ENDOTOXIN (0.8291, p <0.0001) and Hs-CRP (0.7023, p <0.0001). HCY had highest sensitivity (89.71%) and specificity (83.03%) compared with ENDOTOXIN (82.83%, 62.08%) and CRP (73.53%, 50.77%) for predicting small bowel necrosis. The serum HCY cutoff level for the diagnosis of small bowel necrosis was 15.53µmol/L. Conclusions This study provides compelling evidence that homocysteine (HCY) levels can be a useful predictor of irreversible transmural intestinal necrosis that necessitates surgical resection in the setting of adhesive small bowel obstruction. Close monitoring of the HCY serum level could help avoid unnecessary laparotomy and resection, as well as complications due to unnnecessary surgery, and potentially decrease overall mortality rates.

Background Even though more and more cases of laparoscopic central pancreatectomy (LCP) are reported (Machado et al. in Surg Laparosc Endosc Percutan Tech 23(6):486–490, 2013 ; Hong et al. in World J Surg Oncol 10:223, 2012 ; Gonzalez et al. in JOP 14(3):273–276, 2013 , Zhang et al. in J Laparoendosc Adv Surg Tech A 23(11):912–918, 2013 ; Sucandy et al. in N Am J Med Sci 2(9):438–441, 2010 ; Sa Cunha et al. in Surgery 142(3):405–409, 2007 ), the management for pancreatic stumps remains the most technically challenging part which is the same as in pancreatoduodenectomy (PD), making it the bottleneck for laparoscopic pancreatic surgery. In open surgery, various pancreatic reconstruction techniques designed for either pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG) have been attempted to reduce the postoperative pancreatic fistula (POPF), including the binding anastomosis, invented by our team, i.e., binding PG (BPG) and binding PJ, which have been proved to be effective to reduce the POPF (Hong et al. 2012 ; Peng et al. in Ann Surg 245(5):692–698, 2007 ; Peng et al. in Updates Surg 63(2):69–74, 2011 ). However, despite of this, few reports are seen addressing such technique for laparoscopic surgery even though laparoscopic pancreatic surgery is more performed. After a previous successful laparoscopic BPG in a case of laparoscopic CP (LCP; Hong et al. 2012 ) and more than 50 cases of open PD and CP (Peng et al. 2011 ), we further performed laparoscopic BPG in 10 consecutive cases of LCP with satisfactory outcomes. Objective To explore the feasibility and efficacy of LCP with BPG. Methods Between October 2011 and July 2014, LCP with laparoscopic BPG was performed in ten consecutive patients with lesions of benign or low malignancy at the pancreatic neck. Operative and pathological data, complications, hospital stay and details on the surgical techniques were introduced. Results The operations were successfully performed in all the ten cases, with no conversions. The tumor size ranged from 2.0–3.0 to 2.5–3.0 cm, average (2.50 ± 0.35) to (2.66 ± 0.35) cm, and the diameter of pancreatic duct was (1.6–2.1) mm, average (1.71 ± 0.17) mm. Operation time was 170–250 (198.50 ± 25.82) min, and blood loss was 20–300 (125 ± 107.31) mL. Three cases had grade A pancreatic fistula (PF), and one case had delayed gastric emptying, which were all managed with conservative treatment. Upper GI bleeding occurred in one case which was cured with second operation, time for the recovery of bowl movement was 3–5 (4.2 ± 0.8) days, the time for semifluid dieting was 6–10 (8.2 ± 1.5) days, and the hospital stay was 8–20 (12.8 ± 4.63) days. The postoperative fast blood sugar was (6.3 ± 1.6) mmol/L with the normal diet, which was not significantly different from the preoperative data (5.3 ± 0.5) mmol/L ( P  > 0.05). The postoperative pathology was as follows: five cases of cystic serous adenoma, one case of intraductal papillary mucinous neoplasm, two cases of neuroendocrine tumor, and two cases of solid pseudopapillary tumor of pancreas. All the patients were followed up for 7–40 months, no recurrence happened, and no new incidence of diabetes or insufficiency of pancreatic exocrine function occurred. Conclusions LCP with BPG is feasible and safe; the advantages lie in its minimal invasiveness, the efficacy for avoiding PF, and the preservation of the pancreatic endocrine and exocrine function insufficiency, making it an ideal procedure for the benign or low-malignant lesions at the pancreatic neck.

In the current study, we tested the potential anti-pancreatic cancer activity of a novel hydroxamate-based histone deacetylase (HDAC) inhibitor ST-3595. We showed that ST-3595 exerted potent anti-proliferative and cytotoxic activities against both established pancreatic cancer cell lines (PANC-1, AsPC-1, and Mia-PaCa-2), and patient-derived primary cancer cells. It was, however, generally safe to non-cancerous pancreatic epithelial HPDE6c7 cells. ST-3595-induced cytotoxicity to pancreatic cancer cells was associated with significant apoptosis activation. Reversely, the pan caspase inhibitor z-VAD-fmk and the caspase-8 inhibitor z-ITED-fmk alleviated ST-3595-mediated anti-pancreatic cancer activity in vitro. For the mechanism study, ST-3595 inhibited HDAC activity, and induced mitochondrial permeability transition pore (MPTP) opening in pancreatic cancer cells. Inhibition of MPTP, by cyclosporin A, sanglifehrin A, or by cyclophilin-D (Cyp-D) siRNA knockdown, dramatically inhibited ST-3595-induced pancreatic cancer cell apoptosis. Meanwhile, we found that a low concentration of ST-3595 dramatically sensitized gemcitabine-induced anti-pancreatic cancer cell activity in vitro. In vivo, ST-3595 oral administration inhibited PANC-1 xenograft growth in nude mice, and this activity was further enhanced when in combination with gemcitabine. In summary, the results of this study suggest that targeting HDACs by ST-3595 might represent as a novel and promising anti-pancreatic cancer strategy.

Background The feasibility of binding pancreaticogastrostomy in laparoscopic central pancreatectomy is not known. Methods In October 2011, a female patient with a pancreatic neck mass received laparoscopic central pancreatectomy with binding pancreaticogastrostomy. Results The operation was successful. No complications occurred. The operative time was 210 min. Blood loss was 120 ml. On day 11 after the operation, the patient was discharged. The postoperative pathological result showed a 2 × 2 × 2-cm solid pseudopapillary tumor of the pancreas with intrapancreatic infiltration. The surgical margin was negative. Conclusions Laparoscopic central pancreatectomy with binding pancreaticogastrostomy might be feasible, facilitating further study in laparoscopic pancreatoduodenectomy. Trial registration This study was waived from trial registration because it is a retrospective analysis of medical records.

Tumor-associated macrophages especially M2 phenotype macrophages play an important role in tumor progression and the formation of immunosuppressive tumor microenvironment. Previous studies indicated that infiltration of a large number of M2-macrophages was positively associated with a low survival rate and poor prognosis of patients with pancreatic ductal cancer. However, the mechanisms responsible for M2-macrophage polarization remain unclear. Recently, Siglec-15 appears as an emerging target for the normalization of the tumor immune microenvironment. Hence, we detected the Sigelc-15 expression on macrophages by using qPCR and Western blot assay and found that the expression of Siglec-15 was upregulated on M2 macrophages induced by IL-4 and conditioned media from pancreatic ductal cancer. In addition, after knocking out Siglec-15, the expression of M2 phenotype macrophage biomarkers such as Arg1 and CD206 was significantly downregulated. Besides, in our study we also found that Siglec-15 could upregulate the glycolysis of macrophage possibly by interacting with Glut1 to regulate the M2-macrophage polarization. The regulation was also partly dependent on STING, and Glut1-related glycose metabolism was involved in regulating cGAS/STING signaling. When utilizing a subcutaneous transplantation mouse model, we observed that knocking out of Siglec-15 or co-injecting tumor cells with macrophage from Siglec-15 KO mice could significantly inhibit the growth of subcutaneous tumors in mice. Taken together, these findings suggest that Siglec-15 is essential for the M2-macrophage polarization to shape an immune suppressive tumor microenvironment in pancreatic cancer and makes it an attractive target for pancreatic cancer immunotherapy.

Gastric cancer stem cells (GCSCs) have an important role in metastasis and recurrence of gastric cancer, and novel treatment strategies that target GCSCs are urgently required. Although evodiamine (Evo), a derivative of the traditional herbal medicine Evodia rutaecarpa, has been reported to have various biological effects, its effect on GCSCs remains unknown. In order to determine the effect of Evo on apoptosis of GCSCs, an MTS assay, flow cytometry and western blot analysis were performed. The effect of Evo on self-renewal in GCSCs was measured by alterations in the sphere formation ability, the expression of induced-pluripotent stem cell factors, expression of epithelial-to-mesenchymal transition (EMT) factors and oxaliplatin resistance of gastric cancer cells (GCCs). Evo inhibited proliferation, promoted the Bax/B-cell lymphoma 2 ratio and altered active caspase-3 expression of GCSCs. In addition, Evo decreased the sphere formation ability, the expression of Sox2, KLF4, Bmi-1 and Oct4, and oxaliplatin resistance in GCCs. Evo decreased the expression of Slug, Twist, Zeb1 and vimentin, suggesting an inhibitory effect on EMT. Furthermore, the expression of β-catenin, c-Myc and cyclin D1 was decreased in Evo-treated spheroids from GCCs. In conclusion, Evo inhibited the Wnt/β-catenin signaling pathway to inhibit proliferation and stem cell properties of GCSCs and repressed the EMT. The present findings highlight the prospect of Evo as a CSCs-targeted therapy in gastric cancer.

BackgroundThe results of laparoscopic pancreaticoduodenectomy combining with mesentericoportal vein resection and reconstruction (LPD-MPVRs) for pancreatic head adenocarcinoma are rarely reported. The aim of present study was to explore the short- and long-term outcomes of different type of LPD-MPVRs.MethodsPatients who underwent LPD-MPVRs in 14 Chinese high-volume pancreatic centers between June 2014 and December 2020 were selected and compared.ResultsIn total, 142 patients were included and were divided into primary closure (n = 56), end-end anastomosis (n = 43), or interposition graft (n = 43). Median overall survival (OS) and median progress-free survival (PFS) between primary closure and end-end anastomosis had no difference (both P > 0.05). As compared to primary closure and end-end anastomosis, interposition graft had the worst median OS (12 months versus 19 months versus 17 months, P = 0.001) and the worst median PFS (6 months versus 15 months versus 12 months, P < 0.000). As compared to primary closure, interposition graft had almost double risk in major morbidity (16.3 percent versus 8.9 percent) and about triple risk (10 percent versus 3.6 percent) in 90-day mortality, while End-end anastomosis had only one fourth major morbidity (2.3 percent versus 8.9 percent). Multivariate analysis revealed postoperation hospital stay, American Society of Anesthesiologists (ASA) score, number of positive lymph nodes had negative impact on OS, while R0, R1 surgical margin had protective effect on OS. Postoperative hospital stay had negative impact on PFS, while primary closure, end-end anastomosis, short-term vascular patency, and short-term vascular stenosis positively related to PFS.ConclusionsIn LPD-MPVRs, interposition graft had the worst OS, the worst PFS, the highest rate of major morbidity, and the highest rate of 90-day mortality. While there were no differences in OS and PFS between primary closure and end-end anastomosis.

Jiandong Zhang,1,* Kai Zhao,1,* Weihang Zhou,1 Guixing Jiang,1 Ying Ding,2 Yizhuo Zhang,1 Xinyu Dong,1 Defei Hong,1 Xiaolong Liu1 1Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Intensive Care Unit, Sir Run Run Shaw Hospital Qiantang Campus, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaolong Liu, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310020, People’s Republic of China, Tel +86-13588457667, Email liuxiaolong@zju.edu.cn Defei Hong, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310020, People’s Republic of China, Email hongdefi@163.comBackground: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors, with approximately 80% of PDAC patients having locally advanced or metastatic disease at diagnosis. The liver is a predominant site of metastasis and is linked to a particularly poor prognosis. Here, we explored camrelizumab (an anti-programmed cell death-1 antibody) combined with albumin-bound paclitaxel and gemcitabine (AG) in patients with PDAC and liver metastases (PCLM).Methods: In this pilot trial (ChiCTR2000038587), patients received camrelizumab (200 mg on day 1) plus gemcitabine (1000 mg/m2 on days 1 and 8) and albumin-bound paclitaxel (125 mg/m2 on days 1 and 8) every 21-day cycle until disease progression, intolerable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analyses evaluated potential biomarkers associated with survival.Results: From October 2018 to October 2023, 17 patients were enrolled. The median OS was 14.0 months (95% confidence interval [CI], 10.0– 24.0) and the median PFS was 6.4 months (95% CI, 5.2– 10.2). Five patients achieved an objective response (29.4%), with a DCR of 64.7%. Fewer liver metastasis lesions, higher white blood cell-to-lymphocyte ratio, and lower neutrophil-to-lymphocyte ratio were associated with improved PFS and OS (P< 0.05). Grade 3 treatment-related adverse events (TRAEs) included platelet count decreased (2 [11.8%]) and neutrophil count decreased (1 [5.9%]). No grade 4 or 5 TRAEs occurred.Conclusion: Camrelizumab combined with AG demonstrates promising antitumor activity in patients with PCLM, with an acceptable safety profile.Keywords: camrelizumab, chemotherapy, pancreatic ductal adenocarcinoma, liver metastases