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Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.
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Dinaciclib, a cyclin-dependent kinase-5 (CDK5) inhibitor, has significant anti-tumor properties. However, the precise mechanism of dinaciclib requires further investigation. Herein, we investigated the anti-tumor functions and molecular basis of dinaciclib in pancreatic ductal adenocarcinoma (PDAC). PDAC and matched para-carcinoma specimens were collected from the patients who underwent radical resection. Immunohistochemistry was performed to assess CDK5 expression. Cell proliferation ability, migration, and invasion were measured using Cell Counting Kit-8, wound healing, and transwell assay, respectively. The cell cycle and apoptosis were assessed using flow cytometry. Gene expression was examined using RNA-seq and quantitative real-time PCR. Protein expression of proteins was measured by western blot analysis and immunofluorescence microscopy. Tumor-bearing mice were intraperitoneally injected with dinaciclib. CDK5 is highly expressed in PDAC. The expression level of CDK5 was significantly related to tumor size, T stage, and the American Joint Committee on Cancer stage. High CDK5 expression can predict poor survival in PDAC patients. In addition, the expression level of CDK5 might be an independent prognostic factor for PDAC patients. Dinaciclib inhibits the growth and motility of PDAC cells and induces apoptosis and cell cycle arrest in the G2/M phase. Mechanistically, dinaciclib down-regulated yes-associated protein (YAP) mRNA and protein expression by reducing ß-catenin expression. Moreover, dinaciclib significantly inhibited PDAC cell growth in vivo . Our findings reveal a novel anti-tumor mechanism of dinaciclib in which it decreases YAP expression by down-regulating ß-catenin at the transcriptional level rather than by activating Hippo pathway-mediated phosphorylation-dependent degradation.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , beta Catenina/metabolismo , Cateninas/genética , Cateninas/metabolismo , Cateninas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento CelularRESUMO
BACKGROUND: To predict postoperative death even after successful hemostasis in patients with post pancreatoduodenectomy pancreatic fistula-associated hemorrhage (PPFH). METHODS: Patients who underwent pancreatoduodenectomy (PD) between September 2011 and August 2020 were identified. PPFH patients were enrolled in this retrospective case-control study and divided into the Cured and Death groups. Perioperative variables were analyzed, especially the characteristics of PPFH and CT image findings. RESULTS: Among the 2732 consecutive pancreaticoduodenectomies, 63 patients (2.3%) were confirmed to have PPFH. The mortality rate of patients following PPFH was 50.8% (32/63). After univariate and multivariate analysis, organ failure 24 h before initial hemorrhage (P = 0.039, OR = 11.53, 95% CI: 1.14-117.00), CT imaging findings of the operative area bubble sign (P = 0.021, OR = 5.15, 95% CI: 1.28-20.79) and PJ dehiscence (P = 0.016, OR = 8.95, 95% CI: 1.50-53.38) were remained as significant predictive factors of postoperative death for PPFH patients. CONCLUSIONS: Patients following PPFH showed a high mortality rate. Organ failure and CT evidence of pancreaticojejunostomy (PJ) dehiscence and operative area bubble signs before initial hemorrhage may allow early prediction of postoperative death in PPFH patients.
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Pancreatopatias , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Estudos de Casos e Controles , Complicações Pós-Operatórias , Pancreaticojejunostomia/métodos , Fístula Pancreática/cirurgia , Pancreatopatias/cirurgia , Hemorragia , Tomografia Computadorizada por Raios XRESUMO
Immune checkpoint inhibitors (ICIs) are widely used in oncology for their favourable antitumor efficacy. ICI therapy is associated with a unique toxicity profile known as immune-related adverse events (irAEs). One such irAE is ICI-related diabetes mellitus (DM), which is relatively uncommon but can become extremely severe, leading to irreversible impairment of ß-cells, and even lead to death if not promptly recognised and properly managed. The precise mechanisms of ICI-related DM are not well understood. In this review, we summarise the clinical characteristics, pathophysiology, and management of this adverse effect caused by ICI therapy. Deeper investigation of ICI-related DM may contribute to elucidate the molecular mechanisms of classical type 1 DM.
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Diabetes Mellitus , Inibidores de Checkpoint Imunológico , Diabetes Mellitus/induzido quimicamente , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
BACKGROUND: It is technical challenging to perform laparoscopic duodenum-preserving pancreatic head resection (LDPPHR). Only a few case reports and case series of LDPPHR are available in the literature. MATERIALS AND METHODS: From February 2019 to November 2019, 24 cases of LDPPHR were carried out in the Department of Pancreas Surgery, West China Hospital, Sichuan University. Data were prospectively collected in terms of demographic characteristics (age, gender, BMI, and pathological diagnosis), intraoperative variables (operative time, estimated blood loss, transfusion, pancreatic texture, and diameter of main pancreatic duct), and post-operative variables (time for oral intake, post-operative hospital stay, and complications). RESULTS: Nine male patients and fifteen female patients were included in this study. The median age of these patients was 43 years. All patients underwent duodenum-preserving total pancreatic head resection laparoscopically. The median operative time was 255 min. The median estimated blood loss was 200 ml. One patient required blood transfusion. The median post-operative hospital stay was 10 days. Three patients suffered from biliary fistula. Eleven patients (45.8%) suffered from pancreatic fistula; however, only one patient (4.2%) suffered from grade B pancreatic fistula. No patient suffered from grade C pancreatic fistula. One patient with chronic pancreatitis required re-operation for jejunal anastomotic bleeding on the first post-operative day. No patient suffered from gastroparesis, duodenal necrosis, or abdominal bleeding. The 30-day mortality was 0. CONCLUSION: LDPPHR is safe and feasible. Real-time indocyanine green fluorescence imaging may help prevent bile duct injury and bile leakage.
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Sistemas Computacionais , Duodeno/cirurgia , Verde de Indocianina/química , Laparoscopia , Imagem Óptica , Pâncreas/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/métodos , Cuidados Pós-Operatórios , Adulto JovemRESUMO
BACKGROUND: Chronic pancreatitis (CP) is considered to be a risk factor for pancreatic cancer. A retrospective study was conducted to evaluate the incidence of pancreatic cancer after surgery for CP and to determine the risk factors. METHODS: The patients who underwent surgery for histologically documented CP between January 2009 and December 2017 were reviewed. The baseline characteristics, operative data, postoperative complications, and follow-up information were analysed. We calculated standardized incidence ratio on the base of the incidence of pancreatic cancer in the standard population in China. The risk factor for pancreatic cancer was assessed using Cox regression. RESULTS: Among 650 patients, pancreatic cancer was detected in 12 patients (1.8%) after a median follow-up of 4.4 years. The standardized incidence ratio of pancreatic cancer was 68.12 (95% CI, 35.20-118.99). Two independent risk factors for the development of pancreatic cancer in patients with chronic pancreatitis after surgery were identified: time interval to surgery [HR 1.005, 95% CI (1.002-1.008), P = 0.002] and de novo endocrine insufficiency [HR 10.672, 95% CI (2.567-44.372), P = 0.001]. CONCLUSIONS: Patients who require surgery for CP are at a very high risk of developing pancreatic cancer. Early surgical intervention plays a protective role in the development of pancreatic cancer from CP. A high index of suspicion for pancreatic cancer should be maintained in CP patients with de novo postoperative diabetes after surgery.
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Neoplasias Pancreáticas/epidemiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/cirurgia , Adulto , China/epidemiologia , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/prevenção & controle , Pancreaticojejunostomia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o TratamentoRESUMO
Background: Pancreatic cancer (PC) is a lethal disease, especially metastatic PC. And it can be divided into two types: head pancreatic cancer (H-PC) and body and tail pancreatic cancer (BT-PC). Prior studies have proved that they have different overall survival (OS) and should be regarded as two different categories of PC. At present, there remains a gap in the field regarding OS across different primary tumor locations and metastatic sites, as well as the metastatic patterns associated with various primary tumor locations in patients with metastatic PC. Thus, our study aims to address this gap by analyzing data from a large population sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The different prognosis of different primary tumor locations and metastatic sites may indicate that different primary locations and metastatic sites may require different therapy and follow-up strategy. It is hoped that these findings will lay the groundwork for future guideline updates and related research. Methods: Patients with pathologically confirmed stage IV metastatic PC from the National Cancer Institute's SEER program between 2010 and 2015 were included, excluding patients with various tumors, without specifying age, specific sites of metastasis, or OS. Data including age, race, gender, tumor size, T stage, N stage, grade, sites, number of metastatic sites, surgery, radiotherapy, chemotherapy and years of diagnoses were collected from the SEER database. OS was defined as the period from initial diagnosis to the date of death. Specific metastatic sites for the different primary locations of tumor were compared. Survival was analyzed by Cox regression analyses. Results: Overall, 14,406 patients with metastatic PC were included in this research (7,104 of H-PC and 7,302 of BT-PC). Gender proportion, tumor size, T stage, N stage, number of metastatic sites surgery of the primary lesions and radiotherapy were different between BT-PC and H-PC. The proportion of only 1 metastatic site was 68.3% in H-PC compared with 58.3% in the BT-PC. The BT-PC was an independent risk factor for liver metastases compared with the H-PC [odds ratio (OR) =1.510; 95% confidence interval (CI): 1.320-1.727]. No matter for those with multiple metastases, or for those with solitary liver or lung metastases, patients with metastatic H-PC showed better OS (P<0.001, P=0.001, P=0.04, respectively). In patients with solitary liver metastases, worse OS was observed in the BT-PC than the H-PC [hazard ratio (HR) =1.109; 95% CI: 1.046-1.175]. Conclusions: The metastatic BT-PC had worse OS and increased risk to suffer from liver and multiple metastases. Moreover, in patients with solitary metastases, those with liver metastases presented poorest survival.
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OBJECTIVES: To develop a nomogram to predict the aggressiveness of non-functional pancreatic neuroendocrine tumors (NF-pNETs) based on preoperative computed tomography (CT) features. METHODS: This study included 176 patients undergoing radical resection for NF-pNETs. These patients were randomly divided into the training (n = 123) and validation sets (n = 53). A nomogram was developed based on preoperative predictors of aggressiveness of the NF-pNETs which were identified by univariable and multivariable logistic regression analysis. The aggressiveness of NF-pNETs was defined as a composite measure including G3 grading, N+, distant metastases, and/ or disease recurrence. RESULTS: Altogether, the number of patients with highly aggressive NF-pNETs was 37 (30.08 %) and 15 (28.30 %) in the training and validation sets, respectively. Multivariable logistic regression analysis identified that tumor size, biliopancreatic duct dilatation, lymphadenopathy, and enhancement pattern were preoperative predictors of aggressiveness. Those variables were used to develop a nomogram with good concordance statistics of 0.89 and 0.86 for predicting aggressiveness in the training and validation sets, respectively. With a nomogram score of 59, patients with NF-pNETs were divided into low-aggressive and high-aggressive groups. The high-aggressive group had decreased overall survival (OS) and disease-free survival (DFS). Moreover, the nomogram showed good performance in predicting OS and DFS at 3, 5, and 10 years. CONCLUSION: The nomogram integrating CT features helped preoperatively predict the aggressiveness of NF-pNETs and could potentially facilitate clinical decision-making.
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Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Nomogramas , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of -19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.
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OBJECTIVES: To compare the postoperative complications and survival of standard pancreatoduodenectomy (SPD) and extended pancreatoduodenectomy (EPD) in patients with resectable adenocarcinoma of the head of the pancreas. METHODS: Between January 1994 and December 2011, 165 patients with biopsy-proven adenocarcinoma of the pancreatic head were treated in West China Hospital, among whom 93 underwent SPD and 72 had EPD. Complications and survival after the surgery were analyzed retrospectively. RESULTS: The median operation time of the EPD group was longer compared with the SPD group (375 minutes vs.310 minutes, P<0.01), the volume of blood transfusion was larger (700 mL vs.400 mL, P<0.05), while the median hospital stay (13.5 days vs.12 days, P=0.79) and the total complication rates were comparable (34.7% vs.32.4%, P=0.93). The total recurrence rates of the SPD and EPD groups were not significantly different (52.7% vs. 43.1%, P=0.83). No significant differences were found between the SPD and EPD groups in 1-year (81.7% vs. 86.1%), 3-year (38.7% vs. 43.1%), 5-year (16.7% vs. 19.4%), and median survivals (19.8 months vs. 23.2 months, P= 0.52). CONCLUSION: The postoperative complications and survival donot differ significantly between SPD and EPD.
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Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adenocarcinoma/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia/efeitos adversos , Estudos RetrospectivosRESUMO
INTRODUCTION AND IMPORTANCE: Disconnected Pancreatic Duct Syndrome (DPDS) without peripancreatic fluid collections are relatively difficult for endoscopists to manage and usually treated with distal pancreatectomy or pancreaticojejunostomy. However, these procedures are risky for patients with severe edema of pancreatic tissue. We report an original one-stage surgical approach for these patients, namely, the "double-cannula pancreatic gastrostomy method". CASE PRESENTATION: A 38-year-old man was admitted with recurrent acute pancreatitis. ct images suggest pancreatic duct discontinuity syndrome. Intraoperative exploration revealed that pancreas inflammation was severe and distal pancreatectomy or pancreaticojejunostomy were risky. Therefore, we decided to perform a double-cannula pancreatic gastrostomy. A 16F type catheter penetrated the front and back walls of the stomach for gastrostomy, and a 6F catheter was inserted into the pancreatic duct for drainage. We placed the drainage tube of pancreatic duct into the gastrostomy tube to ensure the drainage tube of pancreatic duct could reach the gastric cavity. The gastrostomy tube is led out of the body through the abdominal wall. CLINICAL DISCUSSION: Both endoscopic and surgical approaches have been reported in treating DPDS patients. Internal drainage and excision are common surgical methods. CONCLUSIONS: The double-cannula pancreatic gastrostomy was a safe and effective method in this patient. CORE TIP: In this case, the patient suffered recurrent acute pancreatitis due to disconnected pancreatic duct syndrome. This patient without peripancreatic fluid collections was relatively difficult for endoscopists to manage. However, intraoperative exploration revealed a high risk of distal pancreatectomy or pancreaticojejunostomy. Therefore, we used A double-cannula pancreatic gastrostomy method and successfully treated the complications of pancreatic duct stenosis.
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BACKGROUND: Patients after pancreaticoduodenectomy (PD) showed improved glucose tolerance. Evidence for the effect of extrahepatic cholestasis on impaired glucose homeostasis secondary to ductal adenocarcinoma of the pancreatic head is limited. METHODS: In this prospective cross-sectional study, 50 patients with ductal adenocarcinoma of the pancreatic head were included to assess the effect of extrahepatic cholestasis on glucose tolerance status based on the oral glucose tolerance test (OGTT) before pancreatic surgery. RESULTS: Patients with extrahepatic cholestasis more frequently suffered from worsened impaired glucose homeostasis (prediabetes and new-onset diabetes, 95.2% vs. 58.6%, p = 0.004). Elevated bile acid level was recognized as an independent risk factor for impaired glucose homeostasis (p = 0.024, OR = 6.85). Hepatic insulin clearance (HIC) was significantly higher in patients with elevated bile acid levels (p = 0.001). A strong positive correlation was found between bile acid levels and HIC (r = 0.45, p = 0.001). CONCLUSIONS: This study suggested a connection between elevated bile acid levels and worsened impaired glucose homeostasis through increased insulin clearance function in ductal adenocarcinoma of pancreatic head patients.
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OBJECTIVES: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. METHODS: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. RESULTS: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sarcopenia , Masculino , Humanos , Feminino , Caquexia/diagnóstico , Estudos Retrospectivos , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/cirurgia , Sarcopenia/diagnóstico , Redução de Peso , Prognóstico , Neoplasias PancreáticasRESUMO
BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 µL), and interferon gamma (10(-2)-10(-1) µg/100 µL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) µg/100 µL, P<0.05, 10(-2)-10(-3) µg/100 µL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.
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Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/biossíntese , Colágeno Tipo I/biossíntese , Células Estreladas do Fígado/efeitos dos fármacos , Hormônio do Crescimento Humano/toxicidade , Interferon gama/farmacologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Células Cultivadas , Relação Dose-Resposta a Droga , Imunofluorescência , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Injeções Subcutâneas , Interferon gama/administração & dosagem , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Fenobarbital , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Fatores de TempoRESUMO
Postoperative pancreatic fistula (POPF) is a troublesome complication after pancreatic surgeries, and grade C POPF is the most serious situation among pancreatic fistulas. At present, the incidence of grade C POPF varies from less than 1% to greater than 9%, with an extremely high postoperative mortality rate of 25.7%. The patients with grade C POPF finally undergo surgery with a poor prognosis after various failed conservative treatments. Although various surgical and perioperative attempts have been made to reduce the incidence of grade C POPF, the rates of this costly complication have not been significantly diminished. Hearteningly, several related studies have found that intra-abdominal infection from intestinal flora could promote the development of grade C POPF, which would help physicians to better prevent this complication. In this review, we briefly introduced the definition and relevant risk factors for grade C POPF. Moreover, this review discusses the two main pathways, direct intestinal juice spillover and bacterial translocation, by which intestinal microbes enter the abdominal cavity. Based on the abovementioned theory, we summarize the operation techniques and perioperative management of grade C POPF and discuss novel methods and surgical treatments to reverse this dilemma.
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Currently, 15 randomized controlled trials (RCTs) have been designed to investigate whether neoadjuvant therapy (NAT) benefits patients with resectable pancreatic adenocarcinoma (R-PA) compared to surgery alone. Five of them have acquired results so far; however, corresponding conclusions have not been obtained. We speculated that the reason for this phenomenon could be that some prognostic factors had proven to be adverse through upfront surgery curative patterns, but some of them were not regarded as independent baseline characteristics, which is important to obtaining comparability between the NAT and upfront surgery groups. This fact could cause bias and lead to the difference in the outcomes of RCTs. In this review, we collate data about risk factors (such as tumor size, resection margin, and lymph node status) influencing the prognoses of patients with R-PA from five RCTs and discuss the possible reasons for the varying outcomes.
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OBJECTIVE: To explore the diagnostic methods and reasonable surgical interventions for the chronic obstructive pancreatitis due to the inflammatory lesions at the opening of the pancreatic duct. METHODS: From January 2002 to November 2010 the data of 28 patients who were diagnosed as the chronic obstructive pancreatitis (COP) was retrospectively reviewed. Out of the 28 patients, it was analyzed that the clinical manifestations, diagnostic methods, surgical finding and surgical interventions of the 13 patients who were diagnosed as COP due to the inflammatory lesions at the opening of the pancreatic duct in the exploratory operation accompanying recurrent acute abdominal pain with increased serum amylase and lipase, dilation of entire pancreatic duct on imaging before surgery. The conditions included pain recrudescence, quality of life, pancreatic changes on imaging and the serum amylase and lipase after surgery were recorded. RESULTS: All the 13 patients had clinical manifestations of COP. However, 12 patients had different manifestations on imaging from those chronic pancreatitis imaging due to tumors at the duodenal papilla, ampulla or inner pancreatic duct. Via exploratory operation and magnetic resonance cholangiopancreatography (MRCP), there were short pancreaticobiliary common channel or pancreas divisum existing in most patients. There was no acute abdominal pain with the increased serum amylase and lipase in the 12 patients who receiving the transduodenal mastoid, ampulla and pancreatic ductal opening incision and plasty, the paramastoideus incision and plasty in the visit. CONCLUSIONS: The imaging character of COP due to the inflammatory lesions at the opening of the pancreatic duct is the dilation of the pancreatic duct without the chronic obstruction in the bile duct. The patients with short pancreaticobiliary common channel or pancreas divisum easily suffer COP due to the stenosis of the pancreatic ductal opening caused by the duodenal mastoiditis or paramastoiditis. The local plasty surgery to correct the stenosis at the pancreatic ductal opening and improve the drainage of the pancreatic duct is an easy and effective management.
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Inflamação , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/patologia , Pancreatite Crônica/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
The optimal number of examined lymph nodes (ELN) for staging and impact of nodal status on survival following total pancreatectomy (TP) for pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of this study was to evaluate the prognostic impact of different lymph node status after TP for PDAC.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients who underwent TP for PDAC from 2004 to 2015. We calculated overall survival (OS) of these patients using Kaplan-Meier analysis and Cox proportional hazards model.Overall, 1291 patients were included in the study, with 869 node-positive patients (49.5%). A cut-off points analysis revealed that 19, 19, and 13 lymph nodes best discriminated OS for all patients, node-negative patients, and node-positive patients, respectively. Higher number of ELN than the corresponding cut-off points was an independent predictor for better prognosis [all patients: hazard ratios (HR) 0.786, Pâ=â.002; node-negative patients: HR 0.714, Pâ=â.043; node-positive patients: HR 0.678, Pâ<â.001]. For node-positive patients, 1 to 3 positive lymph nodes (PLN) correlated independently with better survival compared with those with 4 or more PLN (HR 1.433, Pâ=â.002). Moreover, when analyzed in node-positive patients with less than 13 ELN, neither the number of PLN nor lymph node ratio (LNR) was associated with survival. However, when limited node-positive patients with at least 13 ELN, univariate analyses showed that both the number of PLN and LNR were associated with survival, whereas multivariate analyses demonstrated that only number of PLN was consistently associated with survival (HR 1.556, Pâ=â.004).Evaluation at least 19 lymph nodes should be considered as quality metric of surgery in patients who underwent TP for PDAC. For node-negative patients, a minimal number of 19 lymph nodes is adequate to avoid stage migration. For node-positive patients, PLN is superior to LNR in predicting survival after TP, predominantly for those with high number of ELN.
Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Metástase Linfática , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Linfonodos/patologia , Masculino , Neoplasias Pancreáticas/patologia , Prognóstico , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The only curative treatment for pancreatic adenocarcinoma is radical surgical resection. Because of the special anatomic features of pancreatic neck, the selection of optimal surgical procedure for treatment of adenocarcinoma of pancreatic neck has always been a dilemma for surgeons. In this paper, we aim to investigate whether different surgical procedures can affect prognosis in the patient with adenocarcinoma of pancreatic neck. METHODS: We used the surveillance, epidemiology, and end results database to review patients with adenocarcinoma of pancreatic neck diagnosed between 1998 and 2015. We calculated overall survival (OS) and cancer-specific survival (CSS) of these patients using Kaplan-Meier analysis and Cox regression model. RESULTS: Overall, 1443 patients were included in the study, with 12.5% treated with surgical resection. Among them, 30 (18.8%) patients underwent distal pancreatectomy (DP), 105 (65.6%) patients underwent pancreatoduodenectomy (PD), and 25 (15.6%) patients underwent total pancreatectomy (TP). Patients underwent DP were older than these underwent TP (70.5±10.7 vs. 62.2±14.1, P = 0.027). Patients underwent TP had higher percentages of nodal metastasis (N1 stage) than these underwent DP (68.0% vs. 34.5%, P = 0.014). The surgical procedures did not significantly affect either OS times (P = 0.924) or CSS times (P = 0.786) in Kaplan-Meier analysis, even if in any subgroup of AJCC stage. The multivariate Cox regression model showed that types of surgery were not associated with OS and CSS. Higher tumor grade and AJCC stage are independent prognostic factors for OS and CSS. No radiotherapy was associated with a worse CSS (HR 1.610, 95% CI 1.016-2.554, P = 0.043). CONCLUSION: Different surgical procedures did not affect prognosis in the patients with adenocarcinoma of pancreatic neck. TP should be performed in carefully selective patients in high-volume pancreatic centers.