ABSTRACT
PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.
Subject(s)
Chemoradiotherapy , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/mortality , Male , Female , Middle Aged , Aged , Disease-Free Survival , Magnetic Resonance Imaging , Adult , Preoperative Care , Fascia/diagnostic imaging , Neoplasm Staging , Chemotherapy, AdjuvantABSTRACT
Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene-Col6a5-and the major differentially enriched signaling pathway-lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes.
ABSTRACT
Metastatic colorectal cancer with BRAF mutation is a type of highly invasive malignant tumor with poor prognosis and few treatment options. Here, we report a case of a BRAF-mutant and DNA mismatch-repair deficiency colorectal cancer patient with postoperative recurrence as well as abdominal cavity and pelvic metastasis, whose condition was relieved continuously after treatment with a new anti-PD-1 antibody, BGB-A317.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , DNA Mismatch Repair/genetics , Immune Checkpoint Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Abdominal Neoplasms/drug therapy , Abdominal Neoplasms/genetics , Abdominal Neoplasms/secondary , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Aged , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Female , Humans , Immunotherapy , Microsatellite Instability , Mutation , Pelvic Neoplasms/drug therapy , Pelvic Neoplasms/genetics , Pelvic Neoplasms/secondary , Treatment OutcomeABSTRACT
HYPOTHESIS: The transition metal phosphide is one of the promising bifunctional electrocatalysts for overall water splitting. Moreover, the activity of phosphide catalysts can be further enhanced by the cationic vacancy engineering. EXPERIMENTS: The self-growth Ni2P nanosheet arrays with abundant cationic vacancy defects (V-Ni2P/NF) has been synthesized via a facile multi-step reaction process involving hydrothermal, phosphorization and acid-etching of Mn which was doped in Ni2P nanosheets as a sacrificial dopant. Furthermore, the experimental studies and density functional theory (DFT) calculations were carried out to evaluate its electrochemical performance. FINDINGS: The chemical and electrocatalytic property of Ni2P were successfully optimized by cationic vacancy engineering and the obtained V-Ni2P/NF catalyst exhibited superior bifunctional catalytic performance for both hydrogen evolution (HER) and oxygen evolution reaction (OER) compared to pristine Ni2P and Mn-doped Ni2P in alkaline electrolyte. The V-Ni2P/NF can afford the current density of 10â¯mAâ¯cm-2 at a small overpotential of 55â¯mV for HER and 250â¯mV for OER. Additionally, the water electrolysis device assembled by the V-Ni2P/NF electrode as both the anode and cathode just requires a small voltage of 1.59â¯V to achieve 10â¯mAâ¯cm-2 and shows no obvious attenuation for 50â¯h.
ABSTRACT
BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Laparoscopy , Aged , Capecitabine , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Costs and Cost Analysis , Deoxycytidine/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Length of Stay , Leucovorin/therapeutic use , Male , Middle Aged , Organoplatinum Compounds/therapeutic use , Oxaloacetates , Prospective Studies , Quality of Life , Treatment OutcomeABSTRACT
Polycystic ovary syndrome (PCOS) is an endocrine disorder with a high prevalence in women of childbearing age. To date, there is no method of efficiently diagnosing PCOS and curing it completely because its pathomechanism remains unclear. Here, we investigated whether metabolic abnormalities maintain the hyperandrogenism and PCOS-like ovaries and whether the symptoms induced by excess androgen are treatable. We ceased the abnormal dihydrotestosterone (DHT) stimulation to determine changes in PCOS-like mice. After ceasing DHT stimulation, the ovarian morphology and gene expression recovered from the DHT-stimulated status. However, after cessation of DHT stimulation, the hypertrophy of adipose tissues and hepatic steatosis were not significantly restored, and fat accumulation-related gene expression and serum metabolic markers in the mice were altered. These findings showed that the reproductive dysfunction was obviously relieved, but because the metabolic abnormalities were not relieved after the cessation of excess androgen for 30 days, it appears that the latter may not maintain the former.
Subject(s)
Dihydrotestosterone/administration & dosage , Dihydrotestosterone/adverse effects , Hyperandrogenism/chemically induced , Metabolic Syndrome/chemically induced , Metabolic Syndrome/pathology , Polycystic Ovary Syndrome/chemically induced , Adipose Tissue/drug effects , Adipose Tissue/pathology , Animals , Disease Models, Animal , Disease Progression , Female , Gene Expression/drug effects , Hyperandrogenism/blood , Hyperandrogenism/genetics , Metabolic Syndrome/blood , Metabolic Syndrome/genetics , Mice , Mice, Inbred C57BL , Ovary/drug effects , Ovary/pathology , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/genetics , Stimulation, Chemical , Time FactorsABSTRACT
BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. METHODS: Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion. RESULTS: DHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling. CONCLUSIONS: In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.
Subject(s)
Hyperandrogenism/blood , Hyperandrogenism/genetics , Receptors, G-Protein-Coupled/genetics , Testosterone/blood , Animals , Cells, Cultured , Dehydroepiandrosterone , Disease Models, Animal , Estradiol/blood , Female , Hyperandrogenism/chemically induced , Hyperandrogenism/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/pathologyABSTRACT
In this study, we investigated the effects of astragaloside IV (As-IV) on pulmonary fibrosis and its mechanisms of action. Sprague-Dawley rats were used in a model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (BLM). Rats were intraperitoneally injected with As-IV (10, 20, 50 mg/kg) daily for 28 days, while the rats in control and BLM groups were injected with a saline solution. The effects of As-IV treatment on pulmonary injury were evaluated with the lung wet/dry weight ratios, cell counts, and histopathologic. Oxidative stress was evaluated by detecting the levels of malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and reactive oxygen species (ROS) in lung tissue. Inflammation was assessed by measuring the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in bronchoalveolar lavage fluid (BALF). The results indicated that As-IV treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced oxidative stress and inflammation. Our findings indicate that As-IV-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. Its mechanisms of action are associated with inhibiting oxidative stress and inflammatory response. In summary, our study suggests a therapeutic potential of As-IV in the treatment of pulmonary fibrosis.
Subject(s)
Saponins/pharmacology , Triterpenes/pharmacology , Animals , Bleomycin , Dose-Response Relationship, Drug , Inflammation/diagnosis , Inflammation/drug therapy , Oxidative Stress/drug effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/drug therapy , Rats , Rats, Sprague-Dawley , Saponins/administration & dosage , Triterpenes/administration & dosageABSTRACT
Chemerin, a chemokine, plays important roles in immune responses, inflammation, adipogenesis, and carbohydrate metabolism. Our recent research has shown that chemerin has an inhibitory effect on hormone secretion from the testis and ovary. However, whether G protein-coupled receptor 1 (GPR1), the active receptor for chemerin, regulates steroidogenesis and luteolysis in the corpus luteum is still unknown. In this study, we established a pregnant mare serum gonadotropin-human chorionic gonadotropin (PMSG-hCG) superovulation model, a prostaglandin F2α (PGF2α) luteolysis model, and follicle and corpus luteum culture models to analyze the role of chemerin signaling through GPR1 in the synthesis and secretion of gonadal hormones during follicular/luteal development and luteolysis. Our results, for the first time, show that chemerin and GPR1 are both differentially expressed in the ovary over the course of the estrous cycle, with highest levels in estrus and metestrus. GPR1 has been localized to granulosa cells, cumulus cells, and the corpus luteum by immunohistochemistry (IHC). In vitro, we found that chemerin suppresses hCG-induced progesterone production in cultured follicle and corpus luteum and that this effect is attenuated significantly by anti-GPR1 MAB treatment. Furthermore, when the phosphoinositide 3-kinase (PI3K) pathway was blocked, the attenuating effect of GPR1 MAB was abrogated. Interestingly, PGF2α induces luteolysis through activation of caspase-3, leading to a reduction in progesterone secretion. Treatment with GPR1 MAB blocked the PGF2α effect on caspase-3 expression and progesterone secretion. This study indicates that chemerin/GPR1 signaling directly or indirectly regulates progesterone synthesis and secretion during the processes of follicular development, corpus luteum formation, and PGF2α-induced luteolysis.
Subject(s)
Chemokines/metabolism , Corpus Luteum/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Luteolysis/physiology , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/physiology , Superovulation/physiology , Animals , Caspase 3/metabolism , Chorionic Gonadotropin/pharmacology , Corpus Luteum/drug effects , Dinoprost/pharmacology , Estradiol/metabolism , Female , Luteolysis/drug effects , Mice , Phosphatidylinositol 3-Kinases/metabolism , Progesterone/metabolism , Signal Transduction/drug effectsABSTRACT
Gastrointestinal stromal tumors (GISTs) are rare in the rectum. Radical surgery, such as an abdominoperineal resection, is necessary for large rectal GISTs, which can result in the loss of function of involved organs. Imatinib mesylate can be used as perioperative therapy and may reduce tumor size, and it is now approved for use in the adjuvant therapy of locally resected anorectal GISTs. The present study describes two cases of large rectal GISTs, for which abdominoperineal resections were initially planned. The two patients received pre-operative imatinib mesylate treatment, and the therapeutic response was assessed by magnetic resonance imaging. Finally, transsacral local resection was successfully performed for these two GISTs. A macroscopically complete resection was achieved, and microscopically, the resection margin was negative. One patient experienced the complication of rectal leakage, which was successfully managed by drainage. No recurrence occurred in the two patients after more than two years. Pre-operative imatinib mesylate therapy with subsequent transsacral local resection for selected rectal GISTs is a feasible treatment modality and can prevent extended surgery.
ABSTRACT
Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs post-transcriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.
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OBJECTIVE: To investigate the clinical characteristics, diagnosis and therapy of Keutel syndrome, and thereby to minimize the misdiagnosis. METHOD: Data of a case of Keutel syndrome diagnosed at the Provincial Hospital Affiliated to Shandong University were analyzed and related literature were reviewed. RESULT: An 8-month-26-day-old boy was presented with inspiratory and expiratory stridor and wheezing after movement on lung auscultation. His craniofacial appearance was characterized by midfacial hypoplasia with a broad depressed nasal bridge. The nose was small and flat. A grade 2-3/6 systolic murmur was heard between the second and third ribs at left edge of the sternum. The end phalanges of his fingers were thickened. Chest radiograph showed tracheobronchial cartilage calcification and tracheobronchial stenosis. Echocardiographic examination revealed the right pulmonary stenosis. With endoscopic surgery, antiobstructive and antibiotic therapy clinical symptoms were improved. Three weeks later he died of lung reinfection after he was discharged from our hospital. English literature search with "Keutel syndrome" as the key word at "PubMed" showed 22 articles covering 26 patients, and the clinical symptoms were hearing loss (91%), persistent respiratory symptoms (68%), recurrent otitis media/sinusitis (67%), growth development delay (52%) in turn, and signs were brachytelephalangism (100%), low nasal bridge (95%), midfacial hypoplasia (93%), cardiac murmur (69%), and auxiliary examinations showed abnormal cartilage calcification (100%), pulmonary arterial stenosis (72%), tracheobronchial stenosis (50%). CONCLUSION: The diagnosis of Keutel syndrome should be considered in patients with brachytelephalangism, abnormal cartilage calcification, peripheral pulmonary stenosis, and midfacial hypoplasia. Tracheal stenosis was main clinical manifestation in part of patients.
Subject(s)
Abnormalities, Multiple/diagnosis , Calcinosis/diagnosis , Cartilage Diseases/diagnosis , Hand Deformities, Congenital/diagnosis , Pulmonary Valve Stenosis/diagnosis , Tracheal Stenosis/diagnosis , Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/therapy , Bone and Bones/diagnostic imaging , Calcinosis/diagnostic imaging , Calcinosis/therapy , Cartilage/diagnostic imaging , Cartilage Diseases/diagnostic imaging , Cartilage Diseases/therapy , Diagnosis, Differential , Hand Deformities, Congenital/diagnostic imaging , Hand Deformities, Congenital/therapy , Humans , Infant , Male , Pulmonary Valve Stenosis/diagnostic imaging , Pulmonary Valve Stenosis/therapy , Radiography, Thoracic , Retrospective Studies , Tomography, X-Ray Computed , Tracheal Stenosis/diagnostic imagingABSTRACT
OBJECTIVE: To discuss the expression and significance of vascular endothelial growth factor (VEGF) and p53 expression in rat degenerated intervertebral disc (IVD) tissues. METHODS: A total of 78 even-aged Sprague-Dawley (SD) rats (observation group) were chosen to establish a rat IVD degeneration model with anterior limbs and tail-removing method. Three months after modeling, rats were executed and degenerated IVD tissues were obtained for pathological biopsy so as to observe VEGF and p53 expression thereof. Meanwhile, IVD tissues from 8 healthy rats were gained for comparison. RESULTS: Capillary infiltration was found in 62.8% of cases in observation group. Positive expression of VEGF and p53 was seen in 74.4% and 59.0% of cases respectively with a co-expression rate of 53.8%. VEGF and p53 expression in degenerated IVD tissues with capillary infiltration was higher than that in non-infiltration group (P<0.05). CONCLUSIONS: A coordinate expression of VEGF and p53 in rat degenerated IVD tissues is demonstrated, indicating that they are both involved in neovascularization and infiltration, which accelerates IVD degeneration.
Subject(s)
Intervertebral Disc Degeneration/metabolism , Intervertebral Disc/metabolism , Tumor Suppressor Protein p53/metabolism , Vascular Endothelial Growth Factor A/metabolism , Animals , Chi-Square Distribution , Immunohistochemistry , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/pathology , Male , Rats , Rats, Sprague-DawleyABSTRACT
The cellular apoptosis susceptibility (CSE1L) gene has been demonstrated to regulate multiple cellular mechanisms including the mitotic spindle check point as well as proliferation and apoptosis. However, the importance of CSE1L in human colon cancer is largely unknown. In the present study, we examined expression levels of CSE1L mRNA by semiquantitative RT-PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CSE1L expression in the human colon cancer cell line RKO. Changes in CSE1L target gene expression were determined by RT-PCR. Cell proliferation was examined by a high content screening assay. In vitro tumorigenesis was measured by colony-formation assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis. We found CSE1L mRNA to be expressed in human colon cancer cells. Using a lentivirus based RNAi approach, CSE1L expression was significantly inhibited in RKO cells, causing cell cycle arrest in the G2/M and S phases and a delay in cell proliferation, as well as induction of apoptosis and an inhibition of colony growth capacity. Collectively, the results suggest that silencing of CSE1L may be a potential therapeutic approach for colon cancer.
Subject(s)
Apoptosis/genetics , Cellular Apoptosis Susceptibility Protein/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Cell Survival/genetics , Humans , M Phase Cell Cycle Checkpoints/genetics , RNA Interference , RNA, Messenger/biosynthesis , RNA, Small Interfering , S Phase Cell Cycle Checkpoints/geneticsABSTRACT
Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.
Subject(s)
Bronchial Diseases/complications , Calcinosis/complications , Cartilage Diseases/complications , Constriction, Pathologic/complications , Hand Deformities, Congenital/complications , Pulmonary Valve Stenosis/complications , Tracheal Stenosis/complications , Abnormalities, Multiple/diagnosis , Bronchi/abnormalities , Bronchial Diseases/diagnosis , Calcinosis/diagnosis , Cartilage Diseases/diagnosis , Constriction, Pathologic/diagnosis , Fatal Outcome , Hand Deformities, Congenital/diagnosis , Humans , Infant , Male , Pulmonary Valve Stenosis/diagnosis , Tracheal Stenosis/diagnosisABSTRACT
OBJECTIVE: To study the effects of budesonide on hypoxia inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) expression, angiogenesis and airway remodeling in the chronic asthmatic mouse model. METHODS: Thirty female BALB/c mice were randomly divided into normal control, asthma model and treatment groups (10 in each group).The asthmatic mouse model was established via OVA challenge test. Mice in the treatment group were administered with aerosol budesonide (100 µg/kg) an hour before the OVA challenge test from the 28th day. Mice in the control group were treated with PBS instead of OVA. Hematoxylin and eosin staining was performed to observe thickness of the airway wall. Masson staining was used for examing collagen deposition of lung tissues. Angiogenesis and HIF-1α and VEGF expression were measured using immunohistochemistry and Western blot. The relationship of airway wall thickness and vessel area to HIF-1α and VEGF expression was investigated. RESULTS: Vessel area, collagen deposition of lung tissues and airway wall thickness increased in the asthma model group. Levels of HIF-1α and VEGF were also elevated. Administration of budesonide significantly reduced angiogenesis, collagen deposition of lung tissues and airway wall thickening, as well as expression of HIF-1α and VEGF. The vessel area and airway wall thickness were positively correlated with expression of HIF-1α and VEGF. A positive correlation was also found between the expression of HIF-1α and VEGF. CONCLUSIONS: Budesonide can decease angiogenesis and airway remodeling by inhibiting HIF-1α and VEGF expression in asthmatic mice.
Subject(s)
Airway Remodeling/drug effects , Asthma/drug therapy , Bronchodilator Agents/pharmacology , Budesonide/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Vascular Endothelial Growth Factor A/analysis , Animals , Asthma/metabolism , Asthma/pathology , Bronchi/pathology , Disease Models, Animal , Female , Mice , Mice, Inbred BALB C , Neovascularization, PhysiologicABSTRACT
BACKGROUND: Hemolymphangioma of the pancreas is a very rare benign tumor. There were only six reports of this disease until December 2008. Herein, we report a case of giant hemolymphangioma of the pancreas in a 20-year-old girl. CASE PRESENTATION: We describe a 20-year-old girl who presented with a mass in abdominal cavity and epigastric discomfort about a week. Physical examination showed a great abdominal mass. Abdominal computed tomography showed extrinsic duodenal compression due to a large retroperitoneal tumor possibly arising from pancreas. The tumor enucleation was performed and a diagnosis of hemolymphangioma of the pancreas was made. The patient had a complication of chylous leakage, which was successfully managed. The patient is alive and well, after 26 months of follow-up, with no complaints or recurrence. CONCLUSION: From this case and literature, we can conclude that hemolymphangioma of the pancreas in adult is a rare benign tumor, and accurate diagnosis can not be preoperatively established. Tumor resection should be performed whenever possible. The risk of recurrence seems very low.
Subject(s)
Lymphangioma/pathology , Pancreatic Neoplasms/pathology , Adult , Female , Humans , Lymphangioma/diagnosis , Lymphangioma/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgeryABSTRACT
BACKGROUND: This study aimed to assess the efficacy and safety of laparoscopic resection (LR) for rectal cancer. METHODS: A case-control study involving three Chinese medical centers was conducted. Rectal cancer patients undergoing LR were compared with open resection (OR) cases simultaneously from January 2004 to December 2005. Data were collected, and basic characteristics, conversion rate, recovery, complications, adjuvant therapy, and recurrence rate were compared. Analysis was by intention to treat. RESULTS: A total of 335 rectal cancer procedures (115 LR and 220 OR) met the inclusion criteria. The patients' basic characteristics were similar in the two groups (p>0.05). Total mesorectal excision was performed for 85.59% of the patients (201/235), who received anal sphincter preservation. Compared with OR, LR had a shorter incision length, less blood loss, and less need for transfusion, but the operation time was longer (p<0.05). No significant differences were observed between the two groups in positive rates of longitudinal resection margins, numbers of harvested lymph nodes, complication rates during operation and postoperation, and perioperative reoperation and morbidity rates (p>0.05). Postoperative parenteral narcotics were used less in LR than in OR (47.8% vs 62.7%; chi(2)=6.867; p=0.009). The median time until first flatus; resumption of diet, defecation, micturition, and ambulation; and discharge were reduced in LR (p<0.05). Conversion from LR to OR was required by 11.3% of the patients (13/115). The intraoperative complication rate was 30.8% for the patients who underwent conversion. The operation time and postoperative complication rate were the same as for LR alone (p>0.05). The local recurrence rate was 3.7% for the LR group and 4.9% for the OR group (chi (2)=0.209; p=0.647) during the 20-month median follow-up period. CONCLUSIONS: The findings showed that LR for rectal cancer was safe and effective, resulting in faster recovery and a similar complication rate compared with OR. Conversion did not alter the patients' outcomes.
Subject(s)
Colectomy/methods , Laparoscopy/methods , Rectal Neoplasms/surgery , China/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Morbidity/trends , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies , Survival Rate/trends , Treatment OutcomeABSTRACT
OBJECTIVE: To understand the mechanism of effect of conditioned immune response in curing bronchial asthma. METHODS: An experimental asthma modal was produced on healthy BALB/C mice (female, 4 - 6 weeks old) by sensitization and stimulation with ovalbumin (OV A). Totally 105 mice were divided into 7 groups randomly with 15 in each and treated differently: in group CIR(1), noise was used as conditioned stimulus (CS) and budesonide and salbutamol as unconditioned stimulus (UCS) respectively, a conditioned immune response model of mice with asthma was established by the combination of CS and UCS 7 times (7 days), then the mice were given CS only, and the combination were given once a week for 20 weeks. In group CIR(2) saccharin (SAC) was taken as CS, and the other treatments were the same as the group CIR(1). In the group of conventional therapy, the mice were given inhalation of nebulized budesonide and salbutamol only for 20 weeks. In the group of lower dose conventional therapy, the mice were given nebulized inhalation of budesonide and salbutamol for the first 7 days, then once a week for 20 weeks. In the noise group the mice were given noise only everyday for 20 weeks. In SAC group the mice were treated with SAC only everyday for 20 weeks. In the blank control group the mice were treated with placebo for 20 weeks. The mice in all the groups were stimulated with OVA once a day. The mice in the healthy control group were given PBS inhalation for 20 weeks. After 20 weeks therapy, the bronchoalveolar lavage fluid (BALF) was taken for eosinophils (EOS) counting. The spleens were taken to obtain CD4(+)T lymphocytes and the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7), IL-4, IFN-gamma and IL-17 were detected by flow cytometry. RESULTS: (1) The percent of EOS of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that of blank control (P < 0.01), and there was no significant difference among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). (2) The expression of nAChRalpha7, IL-4 and IL-17 of groups CIR(1), CIR(2), conventional therapy and healthy control was much lower than that in blank control group, IFN-gamma was much higher (P < 0.01), and no significant difference was found among groups CIR(1), CIR(2) and conventional therapy (P > 0.05). There was a positive correlation between nAChRalpha7 and IL-4 (r = 0.76, P < 0.01), nAChRalpha7 and IL-17 (r = 0.46, P < 0.01). There was a negative correlation between nAChRalpha7 and IFN-gamma (r = 0.69, P < 0.01). (3) In the groups treated with lower dose of conventional therapy, noise, SAC and blank control, the epithelial tissue of airway were much thicker, the lumens were much narrower, and inflammatory cells and collagen fibers were much more than in the healthy control group, and after therapy, the inflammation in groups CIR(1), CIR(2) and conventional therapy was significantly improved. CONCLUSION: The conditioned immune response models established by both noise and SAC as CS and budesonide and salbutamol as UCS can downregulate nAChRalpha7 on CD4(+)T lymphocytes, regulate the function of CD4(+)T lymphocytes, and achieve the same therapeutic efficacy in treatment of asthma.