Metastatic clear cell sarcoma of the pancreas:A rare case report

BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition:in vitro and in vivo study

AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.

Metastatic clear cell sarcoma of the pancreas:A sporadic cancer

Primary or secondary clear cell sarcoma of the pancreas is an exceedingly rare and aggressive disease.In addition to pathology,molecular analysis is pivotal in differential diagnosis,especially with malignant melanoma.A key aspect in identifying clear cell sarcoma is specific genetic alterations,notably the translocation of t(12;22)(q13;q13),a diagnostic hallmark of this sarcoma subtype,which is absent in malignant melanoma.Treatment of primary clear cell sarcoma of the pancreas is the same as that for adenocarcinoma.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

Shedding light on pancreatic metastasis of clear cell sarcoma:An exceptional journey

This editorial comments on the study by Liu et al investigating pancreatic metastasis of clear cell sarcoma(CCS)published in the World Journal of Clinical Cases.CCS is a rare and aggressive melanocytic tumor,that typically arises from tendons and aponeuroses of the limbs,and metastasizes to the lungs,bones,and brain.However,pancreatic metastasis has rarely been reported,presenting unique diagnostic and therapeutic challenges.Elucidating the clinical characteristics,imaging features,prognostic factors,and treatment outcomes of patients with pancreatic CCS metastasis is crucial.Surgery remains an effective management strategy for CCS.However,the high recurrence rate and low effectiveness of traditional adjuvant treatments necessitate a shift towards more personalized and targeted treatment plans.Research is needed to investigate and validate novel therapeutic approaches specifically tailored to the distinct genetic and molecular characteristics of rare malignancies like CCS.Additionally,the development of late metastases after a long disease-free interval is common in CCS patients.Therefore,routine postoperative surveillance for metastasis using computed tomography,magnetic resonance imaging,bone scans,and positron emission tomography scans is crucial.Moving forward,enhanced collaboration,investigation,and creative thinking among scientists,medical professionals,and legislators are essential to gain a deeper understanding of these rare presentations.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients

Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a major global public health event,resulting in a significant social and economic burden.Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection,recent evidence suggests that it is a complex disease including gastrointestinal symptoms,such as diarrhea,nausea,and vomiting.Moreover,it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms.This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier,chemical barrier,microbial barrier,and immune barrier.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis

AIM:To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis(AP).METHODS:One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included.Patients were classified according to severity of the disease,necrosis ratio and localization.Subjective clinical evaluation and fecal pancreatic elastase-Ⅰ(FPE-Ⅰ)were used for exocrine dysfunction evaluation,and oral glucose tolerance test was completed for endocrine dysfunction.The correlation of disease severity,necrosis ratio and localization with exocrine and endocrine dysfunction were investigated.RESULTS:There were 58 male and 51 female patients,and mean age was 56.5±15.7.Of the patients,35.8%had severe AP(SAP)and 27.5%had pancreatic necrosis.Exocrine dysfunction was identified in 13.7%of the patients[17.9%were in SAP,11.4%were in mild AP(MAP)]and 34.7%of all of the patients had endocrine dysfunction(56.4%in SAP and 23.2%in MAP).In patients with SAP and necrotizing AP(NAP),FPE-Ⅰlevels were lower than the others(P<0.05 and0.001 respectively)and in patients having pancreatic head necrosis or near total necrosis,FPE-1 levels were lower than 200μg/g stool.Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction.Endocrine dysfunction was more significant in patients with SAP and NAP(P<0.001).All of the patients in the necrosectomy group had endocrine dysfunction.CONCLUSION:Patients with SAP,NAP,pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs' therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.

Huge undifferentiated carcinoma of the pancreas with osteoclast-like giant cells

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells(OGCs)is very rare,less than1%of all pancreatic malignancies,and shows worse prognosis than that of invasive ductal adenocarcinoma of the pancreas.We present a case of en bloc resection for a huge undifferentiated carcinoma with OGCs that invaded the stomach and transverse mesocolon.A 67-year female was admitted for left upper quadrant pain and computed tomography demonstrated a mass occupying the lesser sac and abutting the stomach and pancreas.There were no distant metastases and the patient underwent subtotal pancreatectomy with splenectomy,total gastrectomy,and segmental resection of the transverse colon.Histopathological examination confirmed an 11 cm-sized undifferentiated carcinoma of the pancreas with OGCs.Immunohistochemical staining revealed reactivity with pan-cytokeratin in adenocarcinoma component,with vimentin in neoplastic multinucleated cells,with CD45/CD68 in OGCs,and with p53 in tumor cells,respectively.The patient had suffered from multiple bone metastases and survived9 mo after surgery.This case supports the ductal epithelial origin of undifferentiated carcinoma with OGCs and early diagnosis could result in favorable surgical outcomes.Investigations on the surgical role and prog-nostic factors need to be warranted in this tumor.

Effect of tankyrase 1 on autophagy in the corpus cavernosum smooth muscle cells from ageing rats with erectile dysfunction and its potential mechanism

This study compared tankyrase 1 expression and autophagy quantity between erectile dysfunction （ED） and non-ED rats＇ corpus cavernosum smooth muscle cells （CSMCs）. This study aslo explored the effect and possible mechanism of tankyrase 1 on autophagy and cell proliferation in ageing ED rats＇ CSMCs. The intracavernous pres- sure and mean systemic arterial pressure were measured to investigate erectile function so that eight 24-month-old ED and eight 8-month-old male Wistar rats were choosed respectively. The rat CSMCs were isolated and cultured by enzyme digestion, in which tankyrase 1 expression and autophagy quantity were compared. Tankyrase 1 over-expression was induced with plasmid transfection by Lipofectamine^TM. The effect of tankyrase 1 overexpression on proliferation, autophagy and mTOR pathway in 24-month-old ED rats＇ CSMCs was measured by the cell growth curve in MTT assay, cell cycle analysis in flow cytometry （FCM）, key protein expression in Western blot, autophagy quantity in transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 fluorescence. The primary CSMCs were confirmed by immunofluorescence, and the purity was 99.1% in FCM. Compared with that of 8-month-old rats, tankyrase 1 expression and autophagy quantity significantly decreased in 24-month-old ED rats＇ primary CSMCs （P 〈 0.01）. Tankyrase 1 overexpression significantly increased the growth rate （P 〈 0.05） and increased the S phase of cell cycle （P 〈 0.01）. The autophagosome quantity was remarkably increased （P 〈 0.01）, LC3-Ⅰ/Ⅱ and Beclin 1 were upregulated （P 〈 0.01 and P 〈 0.05）, and p-p70S6K （Thr389） was downregulated in 24-month-old ED rat CSMCs （P 〈 0.05）. In conclusion, Tankyrase 1 and autophagy decrease in the CSMCs from aging rats with ED, and tankyrase 1 may have a positive effect on proliferation by enhancing autophagy and regulating the mTOR signalling pathway.

Osteoclastic and pleomorphic giant cell tumors of the pancreas:A review of clinical,endoscopic,and pathologic features

Giant cell tumors of the pancreas come in three varieties-osteoclastic,pleomorphic,and mixed histology.These tumors have distinctive endoscopic,clinical,and cytological features.Giant cell tumors have a controversial histogenesis,with some authors favoring an epithelial origin and others favoring a mesenchymal origin.The true origin of these lesions remains unclear at this time.These are also very rare tumors but proper identification and differentiation from more common pancreatic adenocarcinoma is important.The risk factors of these tumors and the prognosis may be different from those associated with standard pancreatic adenocarcinoma.Recognition of these differences can significantly affect patient care.These lesions have a unique appearance when imaged with endoscopic ultrasound(EUS),and these lesions can be diagnosed via EUS guided Fine Needle Aspiration(FNA).This manuscript will review the endoscopic,clinical,and pathologic features of these tumors.

Granular cell tumor of the pancreas:A case report and review of literature

Granular cell tumors,also called Abrikossof's tumors,were originally described by Abrikossof A in 1926.The f irst case of a pancreatic granular cell tumor was described in 1975 and only 6 cases have been reported.We describe a case of granular cell tumor in the pancreas showing pancreatic duct obstruction.Because imaging studies showed f indings compatible with those of pancreatic carcinoma,the patient underwent distal pancreatectomy.Histological examination showed that the tumor consisted of a nested growth of large tumor cells with ample granular cytoplasm and small round nuclei.The tumor cells expressed S-100 protein and were stained with neuron-specific enolase and periodic acid-Schiff,but were negative for desmin,vimentin,and cytokeratin.The resected tumor was diagnosed as a granular cell tumor.To our knowledge,this is the seventh case of Granular cell tumor of the pancreas to be reported.

Giant cell tumor of the pancreas:a pathological diagnosis with poor prognosis

BACKGROUND: Giant cell tumors are rare and highly malignant tumors of the pancreas. Based on two distinct cell populations, they have been divided into two subtypes corresponding to the osteoclast-like giant cell tumor and the pleomorphic giant cell carcinoma of the pancreas. Distinctive imaging features of the tumors remain uncharacterized. Surgical removal is the only appropriate treatment for them, but responses to chemotherapy or radiotherapy remain undocumented. METHODS: Clinical, radiological, histopathologic, and immuno- histochemical features of two cases of giant cell tumor of the pancreas are presented along with a brief review of the literature. RESULTS: En-bloc resection was done successfully in both cases. The patient with an osteoclast-like giant cell tumor remained disease-free with no clinical or radiological evidence of recurrence at 6 months after surgery. However, the patient with the pleomorphic type died 4 months later due to diffuse pulmonary metastasis. CONCLUSIONS: En-bloc surgical resection is the only appropriate treatment for giant cell tumors. The overall prognosis of these tumors is poorer than that of pancreatic ductal adenocarcinoma, especially the pleomorphic type. More studies are required to document the management and outcomes of the tumors.

The role of regulatory T cells in immune dysfunction during sepsis

BACKGROUND: Although regulatory T cells(Tregs) are key to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the stage of sepsis. This article aimed to review the current literature on the role of Tregs in the pathophysiology of septic response, attempting to investigate the role of Tregs in immune dysfunction during sepsis.DATA SOURCES: A literature search was conducted in January 2014 using the China National Knowledge Infrastructure and Pub Med. Articles on the role of Tregs in immune dysfunction during sepsis were identified.RESULTS: The identified articles indicated that Treg levels can be used for the assessment of the course of sepsis. The inhibition of Treg activity can promote the recovery of immune function.CONCLUSION: Since the mechanism of Tregs is complex during the sepsis, more studies are needed.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Stem cell therapy and diabetic erectile dysfunction:A critical review

Erectile dysfunction(ED)has been identified as one of the most frequent chronic complications of diabetes mellitus(DM).The prevalence of ED is estimated to be about 67.4%in all DM cases worldwide.The pathophysiological process leading to ED involves endothelial,neurological,hormonal,and psychological factors.In DM,endothelial and neurological factors play a crucial role.Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM.The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery.However,these treatments are limited in terms of just relieving the symptoms,but not resolving the cause of the problem.The use of stem cells for treating ED is currently being studied mostly in experimental animals.The stem cells used are derived from adipose tissue,bone,or human urine.Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue.However,research on stem cell therapy for ED in humans remains to be limited.Nevertheless,significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

Acinar cell carcinoma of the pancreas in a young patient with chronic pancreatitis

BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells.Unlike ductal adenocarcinoma,this tumor rarely presents with pancreatitis.METHODS:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and management.RESULTS:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic pancreatitis.Histopathological examination of the tissue extracted revealed an ACC.Duodenopancreatectomy was performed.Six months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy.CONCLUSIONS:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic pancreatitis.Data regarding course,treatment,and prognosis of this tumor are generally lacking.