Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Combining Gemcitabine-Loaded Macrophage-like Nanoparticles and Erlotinib for Pancreatic Cancer Therapy.

Pancreatic cancer is a lethal malignancy with a dismal prognosis. Gemcitabine is currently used to treat pancreatic cancer, but it is limited by significant toxicity. Clinical trials on the combination of gemcitabine and erlotinib reported unsatisfactory outcomes along with concerns of toxicity. The encapsulation of chemotherapy drugs in polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) can alleviate toxicity through targeted delivery and sustained release. In addition, camouflaging the NPs with a macrophage membrane can evade the immune system and further improve tumor homing. We designed gemcitabine-loaded PLGA NPs with a macrophage membrane coating (MPGNPs) to reduce drug toxicity and increase the accumulation in the tumor. The combination of MPGNPs and erlotinib synergistically inhibited pancreatic cancer cell proliferation in vitro and in vivo by targeting the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling pathways. The MPGNPs were also able to evade phagocytosis and achieve passive targeting to the pancreatic tumors. The combination of MPGNPs and erlotinib showed synergistic anti-tumor efficacy in vitro and in vivo. This study provides a proof-of-concept for treating pancreatic cancer with a combination of MPGNPs and erlotinib.

The Impact of Aberrant Hepatic Artery on Resection Margin and Outcomes of Laparoscopic Pancreatoduodenectomy: A Single-Center Report.

BACKGROUND: Variations in the anatomy of the hepatic artery are common. This study was aimed at sharing our experience with identifying and protecting the aberrant hepatic artery (AHA) and discussing its impact on the resection margin and outcomes of laparoscopic pancreatoduodenectomy (LPD). METHODS: A total of 576 patients who underwent LPD between 2015 and 2020 were retrospectively selected and divided into AHA and no AHA groups for this study. The demographics of the patients, pathological features, surgical data, and postoperative complications were further compared and analyzed between the two groups. RESULTS: The AHA group included 127 patients (22.05%). No statistically significant differences were found between the AHA and no AHA groups in the intraoperative data, postoperative complications, and long-term survival with malignant tumor. There was also no significant difference in the R1 rate for pancreatic adenocarcinoma. CONCLUSIONS: AHA appears frequently; however, it does not change the incidence of perioperative adverse events following LPD or the long-term prognosis of malignant tumor. The preservation of AHA during surgery can be achieved with a well-planned approach and careful dissection.

Post-operative procalcitonin and C-reactive protein predict pancreatic fistula after laparoscopic pancreatoduodenectomy.

BACKGROUND: Clinically relevant pancreatic fistula (CRPF) is a serious complication following laparoscopic pancreaticoduodenectomy (LPD). This study aimed to determine if C-reactive protein (CRP) and procalcitonin (PCT) serum levels could be used as early biomarkers to predict CRPF after LPD. METHODS: In this retrospective study, we collected peri-operative data of patients who underwent LPD between January 2019 and November 2019. We compared serum levels of white blood cells (WBC), CRP, and PCT on post-operative days (POD) 1, 2, 3, 5, and 7 between the CRPF and non-CRPF groups and analyzed the predictive risk factors for CRPF. RESULTS: Among the 186 patients included in this study, 18 patients (9.7%) developed CRPF, including 15 and 3 patients with grade B and C fistulas, respectively. The mean WBC, CRP, and PCT levels were higher on most PODs in the CRPF group compared to the non-CRPF group. Receiver operating characteristic (ROC) analysis indicated that CRP levels on POD 2, 5, and 7 can predict CRPF development after LPD, with the area under the curve (AUC) value reaching the highest level on POD 2 (AUC 0.794). PCT levels on POD 2, 3, 5, and 7 were highly predictive of CRPF after LPD. The highest AUC value was achieved on POD 3 [PCT > 2.10 ng/ml (AUC 0.951; sensitivity 88.2%, specificity 92.9%, P < 0.001)]. CONCLUSIONS: Both CRP and PCT levels can be used to predict CRPF development after LPD, with PCT having a higher predictive value.

Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial dysfunction.

Regorafenib, a multiple kinase inhibitor, is recently approved for treatment of patients with advanced hepatocellular carcinoma (HCC). Previous studies demonstrated that regorafenib was a mitochondrial toxicant, which associated with the impairment of mitochondria. Sirt3 is involved in the regulation of mitochondrial function in cancers. This study aimed to investigate the mechanism of Sirt3 involved in the mitochondrial dysfunction which associated with regorafenib treatment in liver cancer cells. We found regorafenib inhibited Sirt3 and p-ERK expression in HCC cells in a dose-dependent manner. Bioinformatics analysis showed that Sirt3 expression was down-regulated in liver cancer tissues and its low expression was correlated with worse overall survival (OS) in liver cancer patients. After transfected with Sirt3 overexpression plasmid, we found that Sirt3 sensitized liver cancer cells to regorafenib and resulted in much more apoptosis with a significant increase of ROS level. However, exogenous antioxidant could not weaken the apoptosis. Mitochondrial membrane potential assay indicated that Sirt3 overexpression accelerated the mitochondrial depolarization process induced by regorafenib and aggravated mitochondrial injury. Cellular oxygen consumption assay showed that mitochondrial dysfunction was caused by the damage of the electron transport chain. The results demonstrated that Sirt3 overexpression promoted the increase of ROS and apoptosis induced by regorafenib through the acceleration of mitochondrial dysfunction by impairing function of the electron transport chain in liver cancer cells. Our studies verified the functional role of Sirt3 in regorafenib treatment and suggested that regorafenib accompanied with Sirt3 activator as a novel treatment strategy for HCC.

Gold nanoparticles-loaded anti-miR221 enhances antitumor effect of sorafenib in hepatocellular carcinoma cells.

Objective: Currently, sorafenib is the main systemic chemotherapy drug for advanced stage of hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicates that sorafenib alone has only moderate antitumor efficacy, and could not inhibit metastasis and progression of disease. MiR-221 plays a role in promoting tumorigenesis in HCC by inhibiting the expression of p27. In this study, we analyzed the synergistic anti-tumor effects of sorafenib and gold nanoparticles-loaded anti-miR221 on HCC cell lines. Methods: Gold nanoparticles-loaded anti-miR221 was investigated and identified by transmission electron microscope, ultraviolet-visible spectroscopy, zeta potential and dynamic light scattering measurements as well as the confocal microscopy and dark-field imaging. Two HCC cell lines were treated with sorafenib and AuNPs-anti-miR221 alone or combination in vitro to investigate the inhibitory effect by CCK-8, live/dead fluorescence staining and colony-forming unit assays. MiR-221/p27/DNMT1 signaling pathway including p27 and DNMT1 was examined by western blot. Results: AuNPs-anti-miR221 can enhance the effect of sorafenib in inhibiting cell proliferation via inactivating miR-221/p27/DNMT1 signaling pathway. Conclusions: Our results demonstrate that sorafenib combined with AuNPs-anti-miR221 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggest the AuNPs-anti-miR221 may be a promising chemosensitizer to sorafenib in the treatment of HCC.

Synergistic Antitumor Effect of Sorafenib in Combination with ATM Inhibitor in Hepatocellular Carcinoma Cells.

Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. In this study, we analyzed the synergistic effect of sorafenib and KU-55933 on the proliferation of HCC cell lines. Methods: Three HCC cell lines were treated with sorafenib and KU-55933 alone or combination in vitro to investigate inhibitory effect by MTT and wound healing assay. Epithelial to mesenchymal transition (EMT) phenotype change was investigated after sorafenib and KU-55933 treatment by microscopy. Akt signaling pathway proteins including p-Akt, p-mTOR and p-p70S6K were examined by western blot. In addition, cleaved PARP and autophage-related proteins LC3A/B were detected by western blot. Results: KU-55933 can enhance the effect of sorafenib in inhibiting cell proliferation and migration, overcoming EMT, inducing cell apoptosis via inactivating Akt signaling pathway and inducing autophage. The combination treatment with sorafenib and KU-55933 resulted in a strong synergistic effect in vitro. Conclusion: Our results demonstrate that sorafenib combined with KU-55933 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggests that KU-55933 may be a promising chemosensitizer to sorafenib in the treatment of HCC.

Targeting IRES-Mediated p53 Synthesis for Cancer Diagnosis and Therapeutics.

While translational regulation of p53 by the internal ribosome entry site (IRES) at its 5'-untranslated region following DNA damage has been widely accepted, the detailed mechanism underlying the translational control of p53 by its IRES sequence is still poorly understood. In this review, we will focus on the latest progress in identifying novel regulatory proteins of the p53 IRES and in uncovering the functional connection between defective IRES-mediated p53 translation and tumorigenesis. We will also discuss how these findings may lead to a better understanding of the process of oncogenesis and open up new avenues for cancer diagnosis and therapeutics.

MicroRNA-133a functions as a tumor suppressor by targeting IGF-1R in hepatocellular carcinoma.

MicroRNAs (miRNAs) are a class of small non-coding RNAs and have critical roles in tumorigenesis and metastasis. A growing body of evidence showed that microRNA-133a (miR-133a) was downregulated and played tumor suppressor roles in gastric, colorectal, bladder, and lung cancer. However, the role and underlying molecular mechanism of miR-133a in hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed the expression of miR-133a in HCC tissues and HCC cell lines. We find that miR-133a was downregulated in HCC tissues and cell lines and that miR-133a expression negatively correlated with tumor differentiation (P < 0.01), TNM stage (P < 0.01), and lymph node metastasis (P < 0.01). Then, functional studies demonstrate that restoration of miR-133a in HepG2 cells significantly suppressed proliferation, colony formation, migration, and invasion, induced cell cycle arrest at G0/G1 stage and cell apoptosis in vitro, and decreased tumor size and weight in a nude mouse HepG2 xenograft model. Using bioinformatics method and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF-1R) as a direct target of miR-133a in HCC cells. Furthermore, overexpression of miR-133a inhibited activation AKT and ERK signal pathway, which contributed to suppression of HCC cell growth. These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of HCC cells by targeting IGF-1R.

Comparison of iodine-125 seed implantation and pancreaticoduodenectomy in the treatment of pancreatic cancer.

OBJECTIVE: This retrospective study compared the advantages and disadvantages of iodine-125 (125I) seed implantation and pancreaticoduodenectomy (PD) in the treatment of pancreatic cancer. METHODS: Patients with diagnosed pancreatic cancer who were treated with 125125I seed implantation (30 patients) or PD (30 patients) in our hospital were evaluated for operative time, bleeding, liver function, time to first bowel movement and normal diet, survival, and medical costs. RESULTS: Compared with patients who underwent PD, those given 125I seed implantation had significantly shorter operative time, less bleeding, higher albumin, shorter periods to bowel movement and normal diet, lower risk of complications, and lower medical costs (P < 0.001, each). The difference of bilirubin level, time to feeding, and median survival were not significant statistically between two treatment grouops. CONCLUSION: For pancreatic cancer patients for whom PD is not appropriate or who refuse PD, 125I seed implantation is a good option.

MS-TCNet: An effective Transformer-CNN combined network using multi-scale feature learning for 3D medical image segmentation.

Medical image segmentation is a fundamental research problem in the field of medical image processing. Recently, the Transformer have achieved highly competitive performance in computer vision. Therefore, many methods combining Transformer with convolutional neural networks (CNNs) have emerged for segmenting medical images. However, these methods cannot effectively capture the multi-scale features in medical images, even though texture and contextual information embedded in the multi-scale features are extremely beneficial for segmentation. To alleviate this limitation, we propose a novel Transformer-CNN combined network using multi-scale feature learning for three-dimensional (3D) medical image segmentation, which is called MS-TCNet. The proposed model utilizes a shunted Transformer and CNN to construct an encoder and pyramid decoder, allowing six different scale levels of feature learning. It captures multi-scale features with refinement at each scale level. Additionally, we propose a novel lightweight multi-scale feature fusion (MSFF) module that can fully fuse the different-scale semantic features generated by the pyramid decoder for each segmentation class, resulting in a more accurate segmentation output. We conducted experiments on three widely used 3D medical image segmentation datasets. The experimental results indicated that our method outperformed state-of-the-art medical image segmentation methods, suggesting its effectiveness, robustness, and superiority. Meanwhile, our model has a smaller number of parameters and lower computational complexity than conventional 3D segmentation networks. The results confirmed that the model is capable of effective multi-scale feature learning and that the learned multi-scale features are useful for improving segmentation performance. We open-sourced our code, which can be found at https://github.com/AustinYuAo/MS-TCNet.

Application of the superior mesenteric artery-first approach in laparoscopic pancreatoduodenectomy: A literature review.

Background: Laparoscopic pancreaticoduodenectomy (LPD) is a complicated surgical procedure that has recently been performed safely. A superior mesenteric artery (SMA)-first approach can allow complete mesopancreas resection, maximizing surgical margins and R0 resection rates. Therefore, the SMA-first approach is recommended. This review is a literature summary of recent updates of the SMA approaches for LPD and informs clinical practice of the advantages of its various approach. Methods: A systematic literature search was performed on the PubMed (MEDLINE) database using truncated word searches and medical subject headings to identify all pertinent published studies. Results: After searching PubMed, 303 studies were identified and reviewed, of which 25 described the SMA-first approach, including the anterior, posterior, right, and left approaches, fully described in 5, 6, 13, and 6 articles, respectively. Conclusions: The SMA-first approach is the standard surgical technique for LPD. This review summarized each SMA-first approach's distinct advantages and indications.

Metabolism-related signalling pathways involved in the pathogenesis and development of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) which formerly known as non-alcoholic fatty liver disease (NAFLD) is one of the causes of liver cirrhosis. Currently, a growing number of liver cirrhosis cases develop on the basis of MASLD, and the pathogenesis of MASLD remains unclear. This paper reviews the research progress on the involvement of different metabolism-related signalling pathways in the pathogenesis and development of MASLD.

In-situ-formed immunotherapeutic and hemostatic dual drug-loaded nanohydrogel for preventing postoperative recurrence of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by an exceedingly high recurrence rate post-surgery, significantly impairing the prognosis of HCC patients. However, a standard in-care strategy for postoperative therapy is still lacking. Although encouraging results have been obtained in a newly published clinical trial for postoperative therapy by targeting the vascular endothelial growth factor (VEGF) and programmed death ligand 1 (anti-PD-L1), its efficacy remains constrained. Combining a hemostatic hydrogel with a nanoparticle-based drug delivery system presents an opportunity to optimize the antitumor effect. Herein, we developed a nanoplatform, termed HMSN@Sor/aP@Gel, comprising a hemostatic fibrin hydrogel and functionalized hollow mesoporous silica nanoparticles (HMSNs) loaded with sorafenib and anti-PD-L1 for locally administered targeted-immunotherapy to prevent the postoperative recurrence and metastasis of HCC. The antitumor mechanism is grounded in dual inhibition of Ras/Raf/MEK/ERK (MAPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathways, synergistically complemented by PD-L1 blockade. HMSN@Sor/aP@Gel facilitates dendritic cell maturation, enhances cytotoxic T-lymphocyte infiltration, promotes the polarization of tumor-associated macrophages to M1 phenotype, induces tumor immunogenic cell death, reverses immunosuppression, and establishes immune memory to counter postoperative recurrence. Animal studies corroborate that HMSN@Sor/aP@Gel-mediated targeted immunotherapy significantly impedes primary and metastatic tumor growth and establishes immune memory to prevent recurrence post-surgery. This investigation presents a promising strategy for postoperative therapy with considerable potential for clinical translation.

A transcriptome based molecular classification scheme for cholangiocarcinoma and subtype-derived prognostic biomarker.

Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called "CORE-37") are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.

Anterior versus posterolateral approach for total laparoscopic splenectomy: a comparative study.

OBJECTIVE: Although the anterior approach is normally used for elective laparoscopic splenectomy (LS), the posterolateral approach may be superior. We have retrospectively compared the effectiveness and safety of these approaches in patients with non-severe splenomegaly scheduled for elective total LS. METHODS: Patients with surgical spleen disorders scheduled for elective LS between March 2005 and June 2011 underwent laparoscopic splenic mobilization via the posterolateral or anterior approach. Main outcome measures included operation time, intraoperative blood loss, frequency of postoperative pancreatic leakage, and length of hospital stay. RESULTS: During the study period, 203 patients underwent LS, 58 (28.6%) via the posterolateral and 145 (71.4%) via the anterior approach. Three patients (1.5%) required conversion to laparotomy due to extensive perisplenic adhesions. The posterolateral approach was associated with significantly shorter operation time (65.0 ± 12.3 min vs. 95.0 ± 21.3 min, P < 0.01), reduced intraoperative blood loss (200.0 ± 23.4 mL vs. 350.0 ± 45.2 mL, P < 0.01), and shorter hospital stay (5.0 ± 2.0 d vs. 9.0 ± 3.0 d, P < 0.01) than the anterior approach. The frequency of pancreatic leakage was slightly lower in patients undergoing LS via the posterolateral than the anterior approach (0.0% vs. 3.4%, P > 0.05). CONCLUSIONS: The posterolateral approach is more effective and safer than the anterior approach in patients without severe splenomegaly (< 30 cm).

Laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel conservation: a retrospective study of 20 cases.

BACKGROUND/AIMS: To compare the outcomes and potential morbidities of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation in patients with benign or low-grade malignant pancreatic lesions. METHODOLOGY: Twenty patients who underwent spleen-preserving distal pancreatectomy were retrospectively analyzed. All the patients had benign or low-grade malignant pancreatic lesions that had not invaded the spleen. Twelve patients underwent Kimura's procedure and eight patients underwent Warshaw's. Perioperative data, and procedure-specific complications were compared between the two groups. RESULTS: Age, gender, and body mass index were comparable between the two groups. Operative time and intraoperative blood loss were significantly lower for patients who underwent Warshaw's procedure than for those who received Kimura's (p <0.05 for both). There were no significant differences between the two groups with regard to perioperative blood transfusions, length of postoperative hospital stays, or complication rates. Splenic infarction and gastric varices developed only in patients who underwent Warshaw's procedure (one case each). CONCLUSIONS: Our results suggest that the Kimura technique should be the first choice for patients with benign or low-grade malignant pancreatic lesions. Warshaw's technique was associated with a higher incidence of several complications. However, Warshaw's can increase the success rate of splenic preservation in some cases.

Outcomes of laparoscopic pancreaticoduodenectomy using a modified technique：346 cases from a single center.

PURPOSE: To study the outcomes of laparoscopic pancreaticoduodenectomy (LPD) using a modified technique. METHODS: Our center used priority approach of uncinate process and artery in the pancreatectomy and duct to mucosa pancreaticojejunostomy with a single stitch in the pancreaticojejunostomy. Herein, we retrospectively reviewed 346 cases of LPD using modified techniques. Basic characteristics, preoperative outcomes, factors associated with unfavorable postoperative outcome, and mortality of patients undergoing LPD were collected and analyzed. RESULTS: The average operative time was 259.31 (35-425) min. The mean duration of pancreaticojejunostomy anastomosis was 31.97 (16-90) min. The mean intraoperative blood loss was 101.76 (0-1200) ml by estimation. Postoperative complications included 14 cases (4.1%) of bile leakage, 9 cases (2.6%) of delayed gastric emptying, 26 cases (7.5%) of postoperative bleeding, 34 cases (9.9%) of organ space infection, 17 cases (4.9%) of pulmonary infection, and 50 cases (14.5%) of POPF. Three factors including postoperative bleeding (OR = 3.502; P = 0.033), positive lymph node (OR = 3.296; P < 0.001), and postoperative chemotherapy (OR = 0.241; P = 0.008) were significantly associated with death of LPD. CONCLUSIONS: The modified technique for LPD presents safety and reliability. Postoperative bleeding and positive lymph node may be associated with worse overall survival, and postoperative chemotherapy may be associated with better overall survival.

New nomogram for predicting lymph node positivity in pancreatic head cancer.

Background: Pancreatic cancer is one of the most malignant cancers worldwide, and it mostly occurs in the head of the pancreas. Existing laparoscopic pancreaticoduodenectomy (LPD) surgical techniques have has undergone a learning curve, a wide variety of approaches for the treatment of pancreatic cancer have been proposed, and the operation has matured. At present, pancreatic head cancer has been gradually changing from "surgeons' evaluation of anatomical resection" to "biologically inappropriate resection". In this study, the risk of lymph node metastasis in pancreatic head cancer was predicted using common preoperative clinical indicators. Methods: The preoperative clinical data of 191 patients with pancreatic head cancer who received LPD in the First Affiliated Hospital of Jilin University from May 2016 to December 2021 were obtained. A univariate regression analysis study was conducted, and the indicators with a significance level of P<0.05 were included in the univariate logistic regression analysis into multivariate. Lastly, a nomogram was built based on age, tumor size, leucocyte,albumin(ALB), and lymphocytes/monocytes(LMR). The model with the highest resolution was selected by obtaining the area under a curve. The clinical net benefit of the prediction model was examined using decision curve analyses.Risk stratification was performed by combining preoperative CT scan with existing models. Results: Multivariate logistic regression analysis found age, tumor size, WBC, ALB, and LMR as five independent factors. A nomogram model was constructed based on the above indicators. The model was calibrated by validating the calibration curve within 1000 bootstrap resamples. The ROC curve achieved an AUC of 0.745(confidence interval of 95%: 0.673-0.816), thus indicating that the model had excellent discriminative skills. DCA suggested that the predictive model achieved a high net benefit in the nearly entire threshold probability range. Conclusions: This study has been the first to investigate a nomogram for preoperative prediction of lymphatic metastasis in pancreatic head cancer. The result suggests that age, ALB, tumor size, WBC, and LMR are independent risk factors for lymph node metastasis in pancreatic head cancer. This study may provide a novel perspective for the selection of appropriate continuous treatment regimens, the increase of the survival rate of patients with pancreatic head cancer, and the selection of appropriate neoadjuvant therapy patients.

IFN-α induced systemic lupus erythematosus complicated with hemophagocytic lymphohistiocytosis: a case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening hyperinflammatory condition characterized by excessive activation of macrophages and T cells and resulted in multi-organ dysfunction. HLH can be a primary disease or secondary to infections, malignancy, and some autoimmune diseases, including adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE). However, it is rare for HLH to occur as a secondary condition to drug-induced lupus erythematosus (DILE). In this report, we present a case of HLH as an unusual complication during SLE treatment in a 31-year-old male patient. The patient initially suffered from active chronic hepatitis B (CHB) and was treated with pegylated INFα-2b (Peg-INFα-2b), tenofovir disoproxil and lamivudine. After 19 months, CHB obtained biochemical and virological response with HBsAg positive to HBsAb. The patient developed fever, headache, and cytopenia after Peg-INFα-2b treatment for 33 months, and laboratory studies revealed that ANA and anti dsDNA were positive. He displayed 5 features meeting the HLH-2004 criteria for diagnosis including fever, pancytopenia, hyperferritinemia, high levels of soluble CD25, and hemophagocytosis on bone marrow biopsy. The patient was initiated with a combination treatment of intravenous methylprednisolone pulse therapy, oral cyclosporine, and etoposide (VP-16), which was followed by a course of oral prednisolone, intravenous cyclophosphamide pulse therapy, and entecavir with complete response. To our knowledge, this is the first report of IFN-α induced SLE complicating with HLH. Physicians should consider the potential autoimmune side effects of IFN-α therapy and be alert to insidious HLH in patients diagnosed with SLE.