Y-Z deformable magnetic ring for the treatment of rectal stricture: A case report and review of literature.

BACKGROUND: Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging, especially for patients who do not respond well to endoscopy. In cases where patients have undergone an enterostomy, the stenosis can be easily resolved through magnetic compression. However, common magnetic compression techniques cannot be performed on those without enterostomy. We designed a novel Y-Z deformable magnetic ring (Y-Z DMR) and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer surgery. CASE SUMMARY: We here report the case of a 57-year-old woman who had undergone a laparoscopic radical rectum resection (Dixon) for rectal cancer. However, she started facing difficulty in defecation 6 months after surgery. Her colonoscopy indicated stenosis of the rectal anastomosis. Endoscopic balloon dilation was performed six times on her. However, the stenosis still showed a trend of gradual aggravation. Because the patient did not undergo an enterostomy, the conventional endoscopic magnetic compression technique could not be performed. Hence, we implemented a Y-Z DMR implemented through the anus under single channel. The magnetic ring fell off nine days after the operation and the rectal stenosis was relieved. The patient was followed up for six months and reported good defecation. CONCLUSION: The Y-Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.

Clinical study of extrahepatic biliary adenoma.

BACKGROUND: Biliary adenomas that occur in the extrahepatic biliary tree are rare. It is difficult to distinguish it from cholangiocarcinoma or cholangiolithiasis by various imaging examinations, and it is very easy to be misdiagnosed. AIM: To evaluate the cumulative experiences including clinical characteristics and treatments of nine patients diagnosed with extrahepatic biliary adenoma admitted to the First Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2022. METHODS: A total of nine patients were included in our study. The laboratory examinations, disease diagnosis, therapy and pathological characteristics, and follow-up of every patient were evaluated. RESULTS: Our cohort consisted of six females and three males with an average diagnosis age of 65.1 years (range 46-87). Six extrahepatic biliary adenomas were located in the common bile ducts and three in the hepatic duct. On initial presentation, all of the patients have symptom of biliary origin, including obstructive jaundice (4/9, 44.4%), abdominal pain (6/9, 66.7%), and fever (3/9, 33.3%). Preoperative imaging examination considered bile duct carcinoma in 6 cases and bile duct calculi in 3 cases. All the patients received surgical treatment and were confirmed by pathology as biliary adenoma. The symptoms improved significantly in all 9 patients after surgery. Seven of nine patients recovered well at follow-up without tumor recurrence. One patient died 2 mo after the surgery due to heart failure. One patient developed jaundice again 8 mo after surgery, underwent endoscopic retrograde cholangiopancreatography and biliary stent placement. CONCLUSION: Benign extrahepatic biliary tumors are rare and difficult to diagnosis preoperatively. Intraoperative choledochoscopy and timely biopsy may offer great advantages.

Magnetic compression anastomosis for sigmoid stenosis treatment: A case report.

BACKGROUND: Endoscopic balloon dilation is a minimally invasive treatment for colorectal stenosis. Magnetic compression anastomosis can be applied against gastrointestinal anastomosis. When combined with endoscopy, it offers a unique approach to the recanalization of colorectal stenosis. CASE SUMMARY: We have reported here the case of a 53-year-old female patient who underwent a descending colostomy due to sigmoid obstruction. Postoperative fistula restoration was not possible in her due to sigmoid stenosis. Accordingly, endoscopic-assisted magnetic compression anastomosis for sigmoid stenosis was performed, and the sigmoid stenosis was recanalized 15 d after the surgery. Subsequently, a reduction colostomy was successfully performed after 10 d. CONCLUSION: This case report proposes a novel minimally invasive treatment approach for colorectal stenosis.

Resveratrol inhibits the expression of RYR2 and is a potential treatment for pancreatic cancer.

Resveratrol is a polyphonous natural compound that has cardioprotective, anticancer, and anti-inflammatory properties. Studies have proved that resveratrol (RES) inhibits cancer cell proliferation, migration, and invasion and promotes apoptosis. Elevated expression of ryanodine receptor type 2 (RYR2) may participate in the pathway responsible for calcium metabolism as well as anti-apoptosis and anti-autophagy events in malignant tumor cells. However, the underlying molecular mechanisms of RES anticancer effects with RYR2 are not completely understood in pancreatic cancer. The aim of the present study was tantamount to study the effect of RES in human pancreatic cancer and investigate the underlying mechanisms of RES. We found that RES inhibits proliferation, migration, and invasion and suppresses RYR2 expression in pancreatic cancer cells. In addition, RYR2 knockdown impedes the proliferation, migration, and invasiveness of pancreatic cancer cells. RYR2 knockdown can also increase PTEN expression, while increased RYR2 expression can inhibit PTEN expression. Moreover, RES can upregulate PTEN expression. Taken together, these results indicate that RES could play an antitumor role by decreasing RYR2 expression.

Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling.

BACKGROUND: Perineural invasion (PNI) is an important pathologic feature of pancreatic cancer, and the incidence of PNI in pancreatic cancer is 70%-100%. PNI is associated with poor outcome, metastasis, and recurrence in pancreatic cancer patients. There are very few treatments for PNI in pancreatic cancer. Honokiol (HNK) is a natural product that is mainly obtained from Magnolia species and has been indicated to have anticancer activity. HNK also has potent neurotrophic activity and may be effective for suppressing PNI. However, the potential role of HNK in the treatment of PNI in pancreatic cancer has not been elucidated. METHODS: In our study, pancreatic cancer cells were treated with vehicle or HNK, and the invasion and migration capacities were assessed by wound scratch assays and Transwell assays. A cancer cell-dorsal root ganglion coculture model was established to evaluate the effect of HNK on the PNI of pancreatic cancer. Western blotting was used to detect markers of EMT and neurotrophic factors in pancreatic tissue. Recombinant TGF-ß1 was used to activate SMAD2/3 to verify the effect of HNK on SMAD2/3 and neurotrophic factors. The subcutaneous tumor model and the sciatic nerve invasion model, which were established in transgenic engineered mice harboring spontaneous pancreatic cancer, were used to investigate the mechanism by which HNK inhibits EMT and PNI in vivo. RESULTS: We found that HNK can inhibit the invasion and migration of pancreatic cancer cells. More importantly, HNK can inhibit the PNI of pancreatic cancer. The HNK-mediated suppression of pancreatic cancer PNI was partially mediated by inhibition of SMAD2/3 phosphorylation. In addition, the inhibitory effect of HNK on PNI can be reversed by activating SMAD2/3. In vivo, we found that HNK can suppress EMT in pancreatic cancer. HNK can also inhibit cancer cell migration along the nerve, reduce the damage to the sciatic nerve caused by tumor cells and protect the function of the sciatic nerve. CONCLUSION: Our results demonstrate that HNK can inhibit the invasion, migration, and PNI of pancreatic cancer by blocking SMAD2/3 phosphorylation, and we conclude that HNK may be a new strategy for suppressing PNI in pancreatic cancer.

The effect of aging on VEGF/VEGFR2 signal pathway genes expression in rat liver sinusoidal endothelial cell.

Liver sinusoidal endothelial cells (LSECs) play a key role in the initiation and neoangiogenesis of liver regeneration. We presume that the abnormity of the VEGF/VEGFR2 and its pathway gene Id1, Wnt2 and HGF expression in aged LSECs may be an important mechanism to affect liver regeneration of the elderly. LSECs from two different groups (adult and old) were isolated in a rodent model, and observed by SEM and TEM. The adult and old rats were underwent 70% partial hepatectomy. The proliferation of hepatocytes and LSECs were analyzed by Immunofluorescence staining. The expression of VEGF/VEGFR2 and its pathway gene in isolated LSECs and liver tissue after hepatectomy were detected by qRT-PCR and Western blot. There is a decreased number of endothelial fenestrae in the LSECs of the old group, compared to the adult group. The old group had a lower expression of VEGF/VEGFR2 and its pathway gene than the adult groups (p < 0.01). The results of western blot were consistent with those of qRT-PCR. The hepatocytes had a high proliferation rate at first 4 days after hepatectomy, and a significantly higher proliferation rate in the adult group. The LSECs began to proliferate after 4 days of hepatectomy, and showed a quantity advantage in the adult group. The adult group had a significantly higher expression of VEGF/VEGFR2 and its pathway gene after hepatectomy than the old group (p < 0.01). LSCEs turn to be defenestration in structure and have a low expression of VEGF/VEGFR2 and its pathway gene with aging.

Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways.

NAF-1 (nutrient-deprivation autophagy factor-1), which is an outer mitochondrial membrane protein, is known to play important roles in calcium metabolism, antiapoptosis, and antiautophagy. Resveratrol, a natural polyphenolic compound, is considered as a potent anticancer agent. Nevertheless, the molecular mechanisms underlying the effects of resveratrol and NAF-1 and their mediation of drug resistance in pancreatic cancer remain unclear. Here, we demonstrate that resveratrol suppresses the expression of NAF-1 in pancreatic cancer cells by inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling. In addition, the knockdown of NAF-1 activates apoptosis and impedes the proliferation of pancreatic cancer cells. More importantly, the targeting of NAF-1 by resveratrol can improve the sensitivity of pancreatic cancer cells to gemcitabine. These results highlight the significance of strategies that target NAF-1, which may enhance the efficacy of gemcitabine in pancreatic cancer therapy.

miR-221/222 induces pancreatic cancer progression through the regulation of matrix metalloproteinases.

MicroRNAs are involved in the initiation and progression of pancreatic cancer. In this study, we showed that miR-221/222 is overexpressed in pancreatic cancer. MiR-221/222 overexpression significantly promoted pancreatic cancer cell proliferation and invasion while inhibiting apoptosis. The expression of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 was increased in miR-221/222 mimic-transfected pancreatic cancer cells. Validation experiments identified TIMP-2 as a direct target of miR-221/222. These data indicate that overexpressed miR-221/222 may play an oncogenic role in pancreatic cancer by inducing the expression of MMP-2 and MMP-9, thus leading to cancer cell invasion.

Aberrant expression of CXCR4 and ß-catenin in pancreatic cancer.

AIM: The stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis and Wingless and INT-1 (Wnt)/ß-catenin pathway has been related to cancer progression. The aim of this study was to investigate the expression of CXCR4 and ß-catenin in pancreatic cancer. PATIENTS AND METHODS: A total of 48 pancreatic cancer samples and 8 normal pancreatic tissues were selected to detect CXCR4 and ß-catenin expression by an immunohistological technique. Spearman and Chi-square analyses were used to study the relation between the protein expression and clinical characteristics. Survival analysis was evaluated by the Kaplan-Meier product limit method. RESULTS: The proportions of CXCR4 and ß-catenin expression on pancreatic cancer cells were significantly higher than in normal pancreas tissues. There was a significant difference in CXRC4 expression levels, lymph node metastasis and TNM stage. Clinical Significance was observed for ß-catenin expression and lymph node metastasis; Kaplan-Meier curves suggested that clinical prognosis is poor for patients expressing CXCR4. Multivariate analysis showed that CXCR4 expression was an independent prognostic factor for pancreatic cancer. CONCLUSION: Both CXCR4 and ß-catenin are abnormally expressed in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.

Vitamin D - pivotal nutraceutical in the regulation of cancer metastasis and angiogenesis.

Various epidemiological studies have demonstrated that vitamin D may play important roles in the pathogenesis and progression of cancer. Vitamin D is one of the most pivotal nutraceuticals whose active metabolite, calcitriol (1,25-dihydroxyvitamin D3), possesses anti-proliferative, pro-apoptotic, and pro-differentiating capabilities. Accumulating evidence indicates that the potential benefits of using vitamin D in cancer are not only anti-cancer cell proliferation which is linked with its anti-inflammatory effects, including the suppression of prostaglandin metabolism and inhibition of NF-κB signaling, but also suppressing tumor metastasis and angiogenesis. Here, we present a systematic summary of the effects of vitamin D in the chemoprevention and chemotherapy of cancer, especially anti-metastatic and anti-angiogenic actions.

Resveratrol ameliorates the deleterious effect of severe acute pancreatitis.

Resveratrol (RES) is a traditional Chinese herbal medicine having anti-inflammatory properties. We sought to explore the role of RES in intestinal injury during severe acute pancreatitis (SAP) in a rat model study. For this purpose, RES-treated and sham-operated (SO) SAP rat models were established, and SAP was induced in rats by injecting 4% sodium taurocholate into the biliary-pancreatic duct. In the RES group, RES was infused intravenously immediately after the SAP induction in rats; SO group served as controls. Histopathological analysis, determination of tissue levels of superoxide dismutase (SOD) and malondialdehyde (MDA) and serum levels of TNF-α as well as ICAM-1 and VCAM-1 expression were carried out at 3, 6, and 12 h following SAP induction. The data show that following SAP induction, SOD levels decreased and MDA levels increased along with ICAM-1 and VCAM-1 expression in the intestine. Serum TNF-α levels increased in the SAP group. Importantly, RES treatment significantly reversed all the pathological changes. In conclusion, this study confirmed the anti-inflammatory properties of RES and demonstrated the prevention of injury to the intestinal barrier in the rat SAP model.

Targeting the L-arginine-nitric oxide pathway for cancer treatment.

The action of L-arginine is mainly dependent on its end-product, nitric oxide (NO). The L-arginine/NO pathway has been confirmed to play an important role in tumor development. Recent findings indicate that NO derived from L-arginine could influence angiogenesis factors, vascular permeability, perivascular-cell recruitment and vessel remodeling and maturation. Additionally, the L-arginine/NO pathway could activate a broad array of genes that are functionally involved in proliferation, metastasis and apoptosis. Interestingly, this pathway plays roles in both tumorigensis and tumor killing. The role of the L-arginine/NO pathway in tumor therapy has been well-studied. Members of this pathway have been reported to be promising therapeutic molecules in tumor therapy. This review article summarizes research data on the roles of the L-arginine/NO pathway in cancer biology and cancer therapy.

Emerging role of resveratrol in the treatment of severe acute pancreatitis.

Severe acute pancreatitis (SAP) develops in 15-20% of patients with acute pancreatitis. The management of SAP is a challenging task owing to the fact that it can lead to morbid conditions like multiple organ failure and systemic inflammatory response syndrome, if left untreated. Resveratrol, a drug used in Chinese traditional medicine has shown potential to treat many symptoms of SAP due to its multiple physiological actions. It possesses anti-inflammatory and anti-oxidative properties, both of which are essential in SAP. NF-kappaB activation is a major source of pro-inflammatory mediators in SAP. Administration of resveratrol can inhibit NF-kappaB activity as well as reduce the concentrations of TNF-alpha, IL-6 and IL-1. It can also scavenge reactive oxygen species that are capable of extensive tissue damage. Furthermore, resveratrol also exhibits anti-apoptotic properties via regulation of apoptotic mediators such as Bax, Bcl-2, and caspase-3. It also plays a role in calcium regulation and alleviates SAP-induced histopathological distortions in the pancreas. These multi-faceted results support the use of resveratrol in SAP and mandate the need for extensive research on this molecule.

hSSTR2 expression and octreotide treatment reverses multidrug resistance of BxPC-3 human pancreatic cancer cells.

Pancreatic cancer is generally refractory to most chemotherapeutic agents. We investigated whether hSSTR2 expression and octreotide treatment reverse multidrug resistance of human pancreatic cancer cells. We used pancreatic cancer cells that were transfected by using a lentivirus expression system, which allowed stable expression of the hSSTR2 gene in the pancreatic cancer cells. BxPC-3 cells were transfected with hSSTR2 through a lentivirus vector pWP XL-MOD-SSTR2 in order to enable the expression of hSSTR2. The transfected cells were treated with different concentrations of octreotide and with the chemotherapeutic agents cisplatin, epirubicin, fluorouracil and gemcitabine. The changes in IC50 following treatment with chemotherapeutic agents were determined, and the expression of different MDR indicating marker genes, multidrug resistance gene-1 (MDR1), multidrug resistance-associated protein 2 (MRP2), and lung resistance-related protein (LRP), were evaluated. Octreotide treatment of the transfected cells significantly decreased the IC50 of chemotherapeutic agents in a dose-dependent manner. hSSTR2 gene transfection decreased MDR1, MRP2 and LRP expression by 57, 47 and 56%, respectively (P<0.01), and octreotide treatment (1.6 microg/ml) for 48 h, decreased it further by 88, 73 and 87<, respectively (P<0.01). These data suggested that the down-regulation of MDR genes is responsible for the improvement in the chemotherapeutic sensitivity of hSSTR2-expressing pancreatic cancer cells, when these cells are subjected to octreotide treatment.

Protective effect of resveratrol in severe acute pancreatitis-induced brain injury.

OBJECTIVES: The aim of this study was to study the effects of resveratrol on severe acute pancreatitis (SAP)-induced brain injury. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into 4 equal groups: sham operation, SAP, resveratrol-treated (RES), and dexamethasone-treated. Each group was evaluated at 3, 6, and 12 hours. Levels of serum myelin basic protein and zonula occludens 1 (Zo-1) were determined by enzyme-linked immunosorbent assay. The brain and pancreatic tissues were examined using electron microscopy. Expressions of Bax, Bcl-2, and caspase-3 were observed using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Western blotting. Cytochrome c was detected using Western blotting alone. RESULTS: Myelin basic protein and Zo-1 levels of the RES group were lower than the SAP group at all time points (P < 0.05). The RES group had significantly improved pathologic brain, increase in Bcl-2 expression, and decrease in Bax and caspases-3 expressions compared with the SAP group. CONCLUSIONS: The degradation of Zo-1 is involved in the pathophysiology of brain injury in SAP; MBP can be used as a marker of brain injury in SAP. The protective effect of resveratrol might be associated with the up-regulation of Bcl-2 and down-regulation of Bax and caspase-3.

Acute pancreatitis: a literature review.

Acute pancreatitis (AP) is an inflammatory disease characterized by steady, acute abdominal pain of varying severity, often radiating from the epigastrium to the back. Its presentation ranges from a self-limiting mild disorder to a more severe and fulminant disease. Severe acute pancreatitis accounts for 30% of all deaths related to pancreatitis. The incidence of AP is increasing progressively with a corresponding increase in the incidence of its risk factors. Alcohol abuse and gallstone migration are the established risk factors for development of AP. In recent years, genetic factors and obesity have also been identified as risk factors responsible for the development of AP. The pathophysiology of AP involves acute inflammation of the acinar cells. Excessive acinar cell injury leads to a condition called systemic inflammatory response syndrome (SIRS). Protracted SIRS is responsible for most of the life-threatening complications associated with AP. Most common AP-related complications include pulmonary, renal, cardiovascular, and central nervous system dysfunction. Thus prompt and accurate diagnosis of AP is of paramount importance. The medical management of AP includes controlling pain, providing adequate nutritional support, and monitoring complications. Endoscopic retrograde cholangiopancreatography and surgery have also shown to reduce the mortality and morbidity associated with AP. Drugs such as resveratrol and rosiglitazone are being investigated as potential candidates for the treatment of AP.

Resveratrol ameliorates lung injury via inhibition of apoptosis in rats with severe acute pancreatitis.

The objective of this study was to evaluate the protective effects of resveratrol on lung injury in rats with severe acute pancreatitis. Ninety-six male Sprague-Dawley rats were randomly classified into 4 equal groups (n = 24): control, model, resveratrol-treated, and dexamethasone-treated. The rats were evaluated at 3, 6, and 12 hours after induction of pancreatitis. The following were assessed: P(a)O(2)by arterial blood gas analysis; pancreatic and lung injury by histology; and ultrastructure of lung tissue by transmission electron microscopy. The authors investigated mitochondrial cytochrome c release and evaluated the Bax, Bcl-2, and caspase-3 expression levels in lung tissue over the time course of apoptosis. Changes in lung cell mitochondrial membrane potential were evaluated by confocal laser scanning microscopy. In the model group, lung congestion, edema, inflammatory-cell infiltration, mitochondrial swelling, and cell apoptosis were apparent. In the resveratrol and dexamethasone groups, the morphological changes of the lungs were alleviated. The expression level of Bcl-2 was significantly higher and those of Bax, caspase-3, and cytochrome c were significantly lesser in the resveratrol group than in the model group. Apoptosis is involved in lung injury associated with severe acute pancreatitis, and resveratrol can ameliorate this injury, thus protecting lung function in rats with severe acute pancreatitis.

Relationship of fibronectin and CD44v6 expression with invasive growth and metastasis of liver cancer.

Fibronectin and CD44v6 are involved in tumor invasion and metastasis. We examined fibronectin and CD44v6 expression in normal liver and liver cancer by immunohistochemistry. Fibronectin expression was identified in 37.5% of liver cancer specimens. Well-differentiated tumors and expansive growth were associated with continuous periacinar, or cytoplasmic and periacinar fibronectin expression; poorly differentiated and invasive tumors showed interrupted periacinar or vascular mesenchymal fibronectin expression. CD44v6 expression was absent in controls but was observed in 67.5% of liver cancers. Increased CD44v6 expression was more common with poor clinical tumor characteristics. FN and CD44v6 are potential markers for determining liver cancer invasion and metastasis.