BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognos...BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.展开更多
BACKGROUND Poorly differentiated thyroid carcinoma(PDTC)is a rare and aggressive form of thyroid cancer.Distant metastasis occurs frequently in PDTC.AIM To determine factors associated with distant metastasis and the ...BACKGROUND Poorly differentiated thyroid carcinoma(PDTC)is a rare and aggressive form of thyroid cancer.Distant metastasis occurs frequently in PDTC.AIM To determine factors associated with distant metastasis and the effects of metastasis,either diagnosed on initial presentation or developing during follow-up,on mortality in PDTC patients.METHODS Patients with PDTC diagnosed between January 1,1985 and July 31,2022 were identified using a thyroid cancer database at a medical center in Taiwan.Factors associated with distant metastasis and cancer-specific survival(CSS)were analyzed using binary logistic analysis and Cox regression,respectively.Survival analysis was conducted using the Kaplan–Meier method.RESULTS The study cohort included 39 patients with PDTC,including 16 with distant metastasis on initial presentation,5 with metastasis during the follow-up period,and 18 with no evidence of metastasis.Older age(≥45 years)was significantly associated with a higher risk of distant metastasis(odds ratio:5.31;95%confi-dence interval:1.27–22.2;P=0.018),while sex,tumor size,T stage,and N stage were not associated with distant metastasis.Patients with metastatic PDTC,either diagnosed at presentation or developing during follow-up,had poorer 5-year CSS rates(55.0%and 40.0%,respectively)than those without metastasis(5-year CSS,93.8%)(P=0.001 for both comparisons).CONCLUSION Older patients with PDTC have an increased risk of distant metastasis.Patients with metastatic PDTC,both diagnosed at presentation and developing during follow-up,have a dismal prognosis.展开更多
BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE ca...BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.展开更多
While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effecti...While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.展开更多
Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissol...Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissolution velocity and adhesiveness to surface/cell membranes.Several strategies are applied for nanocrystals production including precipitation,milling,high pressure homogenization and combination methods such as Nano-Edge^(TM),SmartCrystal and Precipitation-lyophilization-homogenization(PLH)technology.For oral administration,many publications reported useful advantages of nanocrystals to improve in vivo performances i.e.pharmacokinetics,pharmacodynamics,safety and targeted delivery which were discussed in this review.Additionally,transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.展开更多
AIM:To identify the predictive clinicopathological factors for lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to further expand the possibility of using endoscopic mucosal resectio...AIM:To identify the predictive clinicopathological factors for lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to further expand the possibility of using endoscopic mucosal resection (EMR) for the treatment of poorly differentiated EGC. METHODS: Data were collected from 85 poorly- differentiated EGC patients who were surgically treated. Association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size (OR = 5.814, 95% CI = 1.050 - 32.172, P = 0.044), depth of invasion (OR = 10.763, 95% CI = 1.259 - 92.026, P = 0.030) and lymphatic vessel involvement (OR = 61.697, 95% CI = 2.144 - 175.485, P = 0.007) were the significant and independent risk factors for LNM. The LNM rate was 5.4%, 42.9% and 50%, respectively, in poorly differentiated EGC patients with one, two and three of the risk factors, respectively. No LNM was found in 25 patients without the three risk factors. Forty-four lymph nodes were found tohave metastasis, 29 (65.9%) and 15 (34.1%) of the lymph nodes involved were within N1 and beyond N1, respectively, in 12 patients with LNM. CONCLUSION: Endoscopic mucosal resection alone may be sufficient to treat poorly differentiated intramucosal EGC (≤ 2.0 cm in diameter) with no histologically-confirmed lymphatic vessel involvement. When lymphatic vessels are involved, lymph node dissection beyond limited (D1) dissection or D1+ lymph node dissection should be performed depending on the tumor location.展开更多
While the incidence of gastric cancer(GC)in general has decreased worldwide in recent decades,the incidence of diffuse cancer historically comprising poorly cohesive cells-GC(PCC-GC)and including signet ring cell canc...While the incidence of gastric cancer(GC)in general has decreased worldwide in recent decades,the incidence of diffuse cancer historically comprising poorly cohesive cells-GC(PCC-GC)and including signet ring cell cancer is rising.Literature concerning PCC-GC is scarce and unclear,mostly due to a large variety of historically used definitions and classifications.Compared to other histological subtypes of GC,PCC-GC is nevertheless characterized by a distinct set of epidemiological,histological and clinical features which require a specific diagnostic and therapeutic approach.The aim of this review was to provide an update on the definition,classification and therapeutic strategies of PCC-GC.We focus on the updated histological definition of PCC-GC,along with its implications on future treatment strategies and study design.Also,specific considerations in the diagnostic management are discussed.Finally,the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens(5-Fluorouracil,leucovorin,oxaliplatin and docetaxel),the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.展开更多
BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incid...BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.展开更多
AIM:To investigate the predictive factors of lymph node metastasis(LNM) in poorly differentiated early gastric cancer(EGC),and enlarge the possibility of using laparoscopic wedge resection(LWR).METHODS:We retrospectiv...AIM:To investigate the predictive factors of lymph node metastasis(LNM) in poorly differentiated early gastric cancer(EGC),and enlarge the possibility of using laparoscopic wedge resection(LWR).METHODS:We retrospectively analyzed 85 patients with poorly differentiated EGC who underwent surgical resection between January 1992 and December 2010.The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses.Odds ratios(OR) with 95%CI were calculated.We further examined the relationship between the positive number of the three significant predictive factors and the LNM rate.RESULTS:In the univariate analysis,tumor size(P = 0.011),depth of invasion(P = 0.007) and lymphatic vessel involvement(P < 0.001) were significantly associated with a higher rate of LNM.In the multivariate model,tumor size(OR = 7.125,95%CI:1.251-38.218,P = 0.041),depth of invasion(OR = 16.624,95%CI:1.571-82.134,P = 0.036) and lymphatic vessel involvement(OR = 39.112,95%CI:1.745-123.671,P = 0.011) were found to be independently risk clinicopathological factors for LNM.Of the 85 patients diagnosed with poorly differentiated EGC,12(14.1%) had LNM.The LNM rates were 5.7%,42.9% and 57.1%,respectively in cases with one,two and three of the risk factors respectively in poorly differentiated EGC.There was no LNM in 29 patients without the three risk clinicopathological factors.CONCLUSION:LWR alone may be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size,and when lymphatic vessel involvement is absent at postoperative histological examination.展开更多
AIM To investigate the predictive factors of lymph node metastasis(LNM)in poorly differentiated early gastric cancer(EGC);to guide the individual application of a combination of endoscopic submucosal dissection(ESD)an...AIM To investigate the predictive factors of lymph node metastasis(LNM)in poorly differentiated early gastric cancer(EGC);to guide the individual application of a combination of endoscopic submucosal dissection(ESD)and laparoscopic lymph node dissection(LLND)in a suitable subgroup of patients with poorly differentiated EGC.METHODS We retrospectively analyzed 138 patients with poorly differentiated EGC who underwent gastrectomy with lymphadenectomy between January 1990 and December 2015.The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses.Odds ratios(OR)with 95%confidence interval(95%CI)were calculated.We further examined the relationship between the positive number of the significant predictive factors and the LNM rate.RESULTS The tumor diameter(OR=13.438,95%CI:1.773-25.673,P=0.029),lymphatic vessel involvement(LVI)(OR=38.521,95%CI:1.975-68.212,P=0.015)and depth of invasion(OR=14.981,95%CI:1.617-52.844,P=0.024)were found to be independent risk factors for LNM by multivariate analysis.For the 138 patients diagnosed with poorly differentiated EGC,21(15.2%)had LNM.For patients with one,two and three of the risk factors,the LNM rates were 7.7%,47.6%and 64.3%,respectively.LNM was not found in 77 patients that did not have one or more of the three risk factors.CONCLUSION ESD might be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to2 cm in size and when LVI is absent upon postoperative histological examination.ESD with LLND may lead to the elimination of unnecessary gastrectomy in poorly differentiated EGC.展开更多
AIM: To identify clinicopathological factors predictive of lymph node metastasis(LNM) in intramucosal poorly differentiated early gastric cancer(EGC), and further to expand the possibility of using endoscopic submucos...AIM: To identify clinicopathological factors predictive of lymph node metastasis(LNM) in intramucosal poorly differentiated early gastric cancer(EGC), and further to expand the possibility of using endoscopic submucosal dissection(ESD) for the treatment of intramucosal poorly differentiated EGC.METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios(ORs) with 95% confidence intervals(CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component.RESULTS: Tumor size(OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement(OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component(OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7(8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors.CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.展开更多
We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble ...We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.展开更多
BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux(VUR). There is a lack of evidence in literature tho...BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux(VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning.AIM To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR.METHODS Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid(DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months.Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection(UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations.RESULTS During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males(n = 26/31, 83.8%). Patient’s age(mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade Ⅱ(1patient), grade Ⅲ(8 patients), grade Ⅳ(10 patients), and grade Ⅴ(12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same(statistically equal, paired-samples t-test: P = 0.873). The median(range) follow-up duration was 82(60-120)mo. One patient had persistent reflux after surgery(preoperative: grade Ⅳ, postoperative: grade Ⅲ), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17%(22% to 05%) while in another patient, the DRF increased by 12%(25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria(> 150 mg/d) during the follow-up period.CONCLUSION Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.展开更多
Iron overload increases the risk of diabetes via mechanisms of abnormal glucose metabolism: insulin deficiency, insulin resistance, and/or hepatic dysfunction. Iron reduction upregulates glucose uptake and improves he...Iron overload increases the risk of diabetes via mechanisms of abnormal glucose metabolism: insulin deficiency, insulin resistance, and/or hepatic dysfunction. Iron reduction upregulates glucose uptake and improves hepatocytes insulin receptor activity. This study was conducted to examine the effects of iron depletion—via controlled phlebotomy—on the hypoglycemic treatment in poorly controlled type 2 diabetes mellitus (T2DM) patients with non-genetic iron overload. Forty three patients with poorly controlled T2DM and iron overload were divided into 2 groups: iron depletion group and control group. Regular phlebotomy was performed for iron depletion group on monthly basis until serum ferritin reached 20 μg/L or less. Both groups were examined and compared for blood pressure, serum ferritin, lipid profile, HFE-gene, HbA1c, HOMA-IR and number of medicines used for diabetic control. The results had revealed that group differences of HbA1c (-2.64, 95% CI -3.23 to 2.04, p < 0.001) and HOMA-IR (-0.68, 95% CI -0.98 to -0.37, p < 0.001) showed significant decreases in iron depletion group at end of study. Significant decrease in the numbers of hypoglycemic medicines in iron depletion group was shown at end of study (p < 0.001);66.7% of iron depletion group patients were receiving 1 or 2 medicines at end of studyversus none of the control group. Diastolic blood pressure (DBP), triglycerides and LDL-C decreased significantly while HDL-C levels showed significant rise after iron depletion. It can be concluded from the present study that iron depletion therapy is beneficial for improving the efficiency of glycemic control, DBP, and dyslipidemia in poorly controlled type 2 diabetics with iron over load.展开更多
Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further t...Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as thirdline chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partialtumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.展开更多
Objective The aim of this study was to identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possib...Objective The aim of this study was to identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using laparoscopic surgery for the treatment of intramucosal poorly differentiated EGC.展开更多
Objective： Patients with poorly controlled diabetes have more medical complications and are more difficult to manage. The objective of the present study was to evaluate the clinical outcomes of successful implementat...Objective： Patients with poorly controlled diabetes have more medical complications and are more difficult to manage. The objective of the present study was to evaluate the clinical outcomes of successful implementation of an employer initiated community pharmacist-based disease management program for diabetic patients with poorly controlled diabetes. Methods： Employees with poorly controlled diabetes （glycosylated hemoglobin （A1 C） level 〉 7.5%） were identified fi＇om a large diabetes disease management program, in a rural setting in Texas, US. A longitudinal retrospective study was conducted, analyzing clinical indicators in the diabetes patients following the community pharmacist-based disease management program. The program involved a comprehensive drug therapy assessment and individualized disease management education. Primary outcome measured in the present study was A1C levels, assessed at the baseline visit and at the end of the intervention. Results： A total of 64 patients with poorly controlled diabetes were identified. Significant improvement in mean clinical outcome scores was achieved for A1C levels （p = 0.0011）. At the end of the 1 year longitudinal intervention, targeted body mass index and A1C goals were attained by 35.9% （p 〈 0.001） and 15.6% patients, respectively. The 10 patients reaching goal levels post intervention were in the group that had baseline A1C of 7.5 to 9%. However, patients with 〉 9% A1C levels at baseline had a significant reduction （mean 2.1, p 〈 0.001） post intervention. Conclusion： The community pharmacist-based diabetes disease management program improved A1C levels of patients with poorly controlled diabetes.展开更多
About 40%of approved drugs and nearly 90%of drug candidates are poorly water-soluble drugs.Low solubility reduces the drugability.Effectively improving the solubility and bioavailability of poorly water-soluble drugs ...About 40%of approved drugs and nearly 90%of drug candidates are poorly water-soluble drugs.Low solubility reduces the drugability.Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application.This review briefly introduces the conventional solubilization techniques such as solubili-zers,hydrotropes,cosolvents,prodrugs,salt modification,micronization,cyclodextrin inclusion,solid dispersions,and details the crystallization strategies,ionic liquids,and polymer-based,lipid-based,and inorganic-based carriers in improving solubility and bioavailability.Some of the most commonly used approved carrier materials for solubilization techniques are presented.Several approved poorly water-soluble drugs using solubilization techniques are summarized.Furthermore,this review summa-rizes the solubilization mechanism of each solubilization technique,reviews the latest research advances and challenges,and evaluates the potential for clinical translation.This review could guide the selection of a solubilization approach,dosage form,and administration route for poorly water-soluble drugs.Moreover,we discuss several promising solubilization techniques attracting increasing attention worldwide.展开更多
BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly di...BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.展开更多
Aluminum hydroxide adjuvant exhibits a poorly crystalline boehmite(PCB)structure,which demonstrates instability during prolonged storage.In the present study,we systematically investigated the quality alterations of t...Aluminum hydroxide adjuvant exhibits a poorly crystalline boehmite(PCB)structure,which demonstrates instability during prolonged storage.In the present study,we systematically investigated the quality alterations of the adjuvant stored at roo m temperature by analyzing its crystal structure,particle size distribution,electron microscopic characteristics,pH,isoelectric point(pI),and adsorption capacity.These assessments aimed to ensure the effectiveness and safety of vaccine production.Three batches of adjuvants were stored at room temperature for 15 months,and their changes were monitored using X-ray diffraction patterns,transmission electron microscopy(TEM),pH measurements,pI determination,and adsorption capacity analysis.X-ray diffraction revealed that the crystalline phases of aluminum hydroxide initially exhibited a PCB structure,which became progressively more ordered during storage.Notably,after 12 months,a new diffraction peak emerged at 18.2°2θ,with its intensity increasing over time.This corresponded to the formation of highly crystalline gibbsite and bayerite,which compromised the stability of the adjuvant.Furthermore,the pH and pI values decreased during storage,reflecting a decline in the chemical stability of the adjuvant.Comprising nanoparticles with a mean diameter of 130 nm,the adjuvant maintained a high surface area and excellent adsorption capacity.The adsorption rate at 8 mg BSA/mg Al3+consistently exceeded 97%,with no statistically significant differences observed between the adsorption capacities at 1 and 15 months(P>0.05).This indicated that the nanoparticle aluminum hydroxide adjuvant sustained high adsorption efficiency throughout the storage period,underscoring its reliability as a vaccine adsorbent.However,in the later stages of storage,the emergence of highly crystalline gibbsite and bayerite,coupled with declines in pH and pI,negatively impacted the adjuvant’s stability.Based on these findings,we recommended that aluminum hydroxide adjuvants should not be stored at room temperature for longer than 12 months to preserve their quality and efficacy.展开更多
文摘BACKGROUND The prognosis of patients with poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)is dismal and related research is limited.AIM To investigate the prognostic factors,and validate a novel prognostic nomogram for PDGNEN patients.METHODS We conducted a retrospective study using clinical and pathological data from PDGNEN patients treated at the First Medical Center of the Chinese PLA General Hospital from January 2000 to June 2023.Overall survival(OS)differences were assessed with the Log-rank test and Kaplan-Meier survival curves.Cox regression analysis identified independent risk factors for prognosis.Model performance was evaluated using Harrell’s concordance index,receiver operating characteristic analysis,area under the curve,calibration curves,and decision curve analysis(UDC),including the area under the UDC.RESULTS The study included 336 patients(227 with neuroendocrine carcinoma and 109 with mixed adenoneuroendocrine carcinoma).The average age was 62.7 years.The cohort comprised 80(24.7%)patients in stage I,146(42.9%)in stage II,62(18.1%)in stage III,and 48(14.3%)in stage IV.Significant differences in OS were observed across tumor-node-metastasis stages(P<0.001).Multivariate analysis showed age,Ki-67 index,invasion depth,lymph node metastasis,distant metastasis,and platelet-to-lymphocyte ratio as independent risk factors.We developed a nomogram with a concordance index of 0.779(95%confidence interval:0.743-0.858).Receiver operating characteristic analysis showed area under the curves for 1-year,3-year,and 5-year OS predictions of 0.865,0.850,and 0.890,respectively.The calibration curve demonstrated good agreement with actual outcomes.The area under the UDC for the nomogram vs the 8th American Joint Committee on Cancer tumor-node-metastasis staging system were 0.047 vs 0.027,0.291 vs 0.179,and 0.376 vs 0.216 for 1-year,3-year,and 5-year OS,respectively.CONCLUSION PDGNENs are predominantly found in older men,often in advanced stages at diagnosis,resulting in poor prognosis.The established nomogram demonstrates strong predictive capability and clinical utility.
基金Supported by New Taipei Municipal TuCheng Hospital(Built and Operated by Chang Gung Medical Foundation),New Taipei City,Taiwan,No.CORPVVP0031the National Science and Technology Council of Taiwan,No.NSTC 112-2314-B-182A-111-MY3.
文摘BACKGROUND Poorly differentiated thyroid carcinoma(PDTC)is a rare and aggressive form of thyroid cancer.Distant metastasis occurs frequently in PDTC.AIM To determine factors associated with distant metastasis and the effects of metastasis,either diagnosed on initial presentation or developing during follow-up,on mortality in PDTC patients.METHODS Patients with PDTC diagnosed between January 1,1985 and July 31,2022 were identified using a thyroid cancer database at a medical center in Taiwan.Factors associated with distant metastasis and cancer-specific survival(CSS)were analyzed using binary logistic analysis and Cox regression,respectively.Survival analysis was conducted using the Kaplan–Meier method.RESULTS The study cohort included 39 patients with PDTC,including 16 with distant metastasis on initial presentation,5 with metastasis during the follow-up period,and 18 with no evidence of metastasis.Older age(≥45 years)was significantly associated with a higher risk of distant metastasis(odds ratio:5.31;95%confi-dence interval:1.27–22.2;P=0.018),while sex,tumor size,T stage,and N stage were not associated with distant metastasis.Patients with metastatic PDTC,either diagnosed at presentation or developing during follow-up,had poorer 5-year CSS rates(55.0%and 40.0%,respectively)than those without metastasis(5-year CSS,93.8%)(P=0.001 for both comparisons).CONCLUSION Older patients with PDTC have an increased risk of distant metastasis.Patients with metastatic PDTC,both diagnosed at presentation and developing during follow-up,have a dismal prognosis.
基金The Health Science and Technology Foundation of Inner Mongolia,No.202201436Science and Technology Innovation Foundation of Inner Mongolia,No.CXYD2022BT01.
文摘BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.
基金This work was supported by the National Research Foundation of South Korea(NRF)grants funded by the South Korean government(MEST)(No.2022R1A2C2004197,RS-2024-00407053 and RS-2023-00208448).
文摘While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.
基金the Thailand Research Fund through Thai Basic Research Grant(BRG5680020 to V.B.J.)the Royal Golden Jubilee Ph.D.Program and Mahidol。
文摘Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissolution velocity and adhesiveness to surface/cell membranes.Several strategies are applied for nanocrystals production including precipitation,milling,high pressure homogenization and combination methods such as Nano-Edge^(TM),SmartCrystal and Precipitation-lyophilization-homogenization(PLH)technology.For oral administration,many publications reported useful advantages of nanocrystals to improve in vivo performances i.e.pharmacokinetics,pharmacodynamics,safety and targeted delivery which were discussed in this review.Additionally,transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.
基金Gastric Cancer Laboratory of China Medical University,Shenyang,Liaoning Province,China
文摘AIM:To identify the predictive clinicopathological factors for lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC) and to further expand the possibility of using endoscopic mucosal resection (EMR) for the treatment of poorly differentiated EGC. METHODS: Data were collected from 85 poorly- differentiated EGC patients who were surgically treated. Association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis showed that tumor size (OR = 5.814, 95% CI = 1.050 - 32.172, P = 0.044), depth of invasion (OR = 10.763, 95% CI = 1.259 - 92.026, P = 0.030) and lymphatic vessel involvement (OR = 61.697, 95% CI = 2.144 - 175.485, P = 0.007) were the significant and independent risk factors for LNM. The LNM rate was 5.4%, 42.9% and 50%, respectively, in poorly differentiated EGC patients with one, two and three of the risk factors, respectively. No LNM was found in 25 patients without the three risk factors. Forty-four lymph nodes were found tohave metastasis, 29 (65.9%) and 15 (34.1%) of the lymph nodes involved were within N1 and beyond N1, respectively, in 12 patients with LNM. CONCLUSION: Endoscopic mucosal resection alone may be sufficient to treat poorly differentiated intramucosal EGC (≤ 2.0 cm in diameter) with no histologically-confirmed lymphatic vessel involvement. When lymphatic vessels are involved, lymph node dissection beyond limited (D1) dissection or D1+ lymph node dissection should be performed depending on the tumor location.
文摘While the incidence of gastric cancer(GC)in general has decreased worldwide in recent decades,the incidence of diffuse cancer historically comprising poorly cohesive cells-GC(PCC-GC)and including signet ring cell cancer is rising.Literature concerning PCC-GC is scarce and unclear,mostly due to a large variety of historically used definitions and classifications.Compared to other histological subtypes of GC,PCC-GC is nevertheless characterized by a distinct set of epidemiological,histological and clinical features which require a specific diagnostic and therapeutic approach.The aim of this review was to provide an update on the definition,classification and therapeutic strategies of PCC-GC.We focus on the updated histological definition of PCC-GC,along with its implications on future treatment strategies and study design.Also,specific considerations in the diagnostic management are discussed.Finally,the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens(5-Fluorouracil,leucovorin,oxaliplatin and docetaxel),the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.
基金National Key R&D Program of China,No.2019YFB1309704。
文摘BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.
文摘AIM:To investigate the predictive factors of lymph node metastasis(LNM) in poorly differentiated early gastric cancer(EGC),and enlarge the possibility of using laparoscopic wedge resection(LWR).METHODS:We retrospectively analyzed 85 patients with poorly differentiated EGC who underwent surgical resection between January 1992 and December 2010.The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses.Odds ratios(OR) with 95%CI were calculated.We further examined the relationship between the positive number of the three significant predictive factors and the LNM rate.RESULTS:In the univariate analysis,tumor size(P = 0.011),depth of invasion(P = 0.007) and lymphatic vessel involvement(P < 0.001) were significantly associated with a higher rate of LNM.In the multivariate model,tumor size(OR = 7.125,95%CI:1.251-38.218,P = 0.041),depth of invasion(OR = 16.624,95%CI:1.571-82.134,P = 0.036) and lymphatic vessel involvement(OR = 39.112,95%CI:1.745-123.671,P = 0.011) were found to be independently risk clinicopathological factors for LNM.Of the 85 patients diagnosed with poorly differentiated EGC,12(14.1%) had LNM.The LNM rates were 5.7%,42.9% and 57.1%,respectively in cases with one,two and three of the risk factors respectively in poorly differentiated EGC.There was no LNM in 29 patients without the three risk clinicopathological factors.CONCLUSION:LWR alone may be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2.0 cm in size,and when lymphatic vessel involvement is absent at postoperative histological examination.
文摘AIM To investigate the predictive factors of lymph node metastasis(LNM)in poorly differentiated early gastric cancer(EGC);to guide the individual application of a combination of endoscopic submucosal dissection(ESD)and laparoscopic lymph node dissection(LLND)in a suitable subgroup of patients with poorly differentiated EGC.METHODS We retrospectively analyzed 138 patients with poorly differentiated EGC who underwent gastrectomy with lymphadenectomy between January 1990 and December 2015.The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses.Odds ratios(OR)with 95%confidence interval(95%CI)were calculated.We further examined the relationship between the positive number of the significant predictive factors and the LNM rate.RESULTS The tumor diameter(OR=13.438,95%CI:1.773-25.673,P=0.029),lymphatic vessel involvement(LVI)(OR=38.521,95%CI:1.975-68.212,P=0.015)and depth of invasion(OR=14.981,95%CI:1.617-52.844,P=0.024)were found to be independent risk factors for LNM by multivariate analysis.For the 138 patients diagnosed with poorly differentiated EGC,21(15.2%)had LNM.For patients with one,two and three of the risk factors,the LNM rates were 7.7%,47.6%and 64.3%,respectively.LNM was not found in 77 patients that did not have one or more of the three risk factors.CONCLUSION ESD might be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to2 cm in size and when LVI is absent upon postoperative histological examination.ESD with LLND may lead to the elimination of unnecessary gastrectomy in poorly differentiated EGC.
文摘AIM: To identify clinicopathological factors predictive of lymph node metastasis(LNM) in intramucosal poorly differentiated early gastric cancer(EGC), and further to expand the possibility of using endoscopic submucosal dissection(ESD) for the treatment of intramucosal poorly differentiated EGC.METHODS: Data for 81 surgically treated patients with intramucosal poorly differentiated EGC were collected, and the association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios(ORs) with 95% confidence intervals(CIs) were calculated. Several clinicopathologic factors were investigated to identify predictive factors for lymph nodes metastasis, including gender, age, family history of gastric cancer, number of tumors, tumor location, ulceration, tumor size, macroscopic type, lymphatic vessel involvement, and signet-ring-cell component.RESULTS: Tumor size(OR = 7.273, 95%CI: 1.246-29.918, P = 0.042), lymphatic vessel involvement(OR = 42.219, 95%CI: 1.923-97.052, P = 0.018) and signet-ring-cell component(OR = 17.513, 95%CI: 1.647-77.469, P = 0.034) that were significantly associated with LNM by univariate analysis, were found to be significant and independent risk factors for LNM by multivariate analysis. However, gender, age, family history of gastric cancer, number, location, ulceration and macroscopic type of tumor were found not to be associated with LNM. Of these 81 patients diagnosed with intramucosal poorly differentiated EGC, 7(8.6%) had LNM. The LNM rates were 9.1%, 22.2% and 57.1%, respectively, in cases with one, two and three of the risk factors. There was no LNM in 54 patients without the three risk clinicopathological factors.CONCLUSION: Tumor size, lymphatic vessel involvement and signet-ring-cell component are independently associated with the presence of LNM in intramucosal poorly differentiated EGC. Thus, these three risk factors may be used as a simple criterion to expand the possibility of using ESD for the treatment of intramucosal poorly differentiated EGC.
基金This work was supported by National Basic Research Program of China(973 Program)(2009CB930300)National Natural Science Foundation of China(81072605)Shenyang Special Fund for Exploration of Intellectual Resources.
文摘We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.
文摘BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux(VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning.AIM To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR.METHODS Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid(DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months.Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection(UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations.RESULTS During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males(n = 26/31, 83.8%). Patient’s age(mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade Ⅱ(1patient), grade Ⅲ(8 patients), grade Ⅳ(10 patients), and grade Ⅴ(12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same(statistically equal, paired-samples t-test: P = 0.873). The median(range) follow-up duration was 82(60-120)mo. One patient had persistent reflux after surgery(preoperative: grade Ⅳ, postoperative: grade Ⅲ), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17%(22% to 05%) while in another patient, the DRF increased by 12%(25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria(> 150 mg/d) during the follow-up period.CONCLUSION Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.
文摘Iron overload increases the risk of diabetes via mechanisms of abnormal glucose metabolism: insulin deficiency, insulin resistance, and/or hepatic dysfunction. Iron reduction upregulates glucose uptake and improves hepatocytes insulin receptor activity. This study was conducted to examine the effects of iron depletion—via controlled phlebotomy—on the hypoglycemic treatment in poorly controlled type 2 diabetes mellitus (T2DM) patients with non-genetic iron overload. Forty three patients with poorly controlled T2DM and iron overload were divided into 2 groups: iron depletion group and control group. Regular phlebotomy was performed for iron depletion group on monthly basis until serum ferritin reached 20 μg/L or less. Both groups were examined and compared for blood pressure, serum ferritin, lipid profile, HFE-gene, HbA1c, HOMA-IR and number of medicines used for diabetic control. The results had revealed that group differences of HbA1c (-2.64, 95% CI -3.23 to 2.04, p < 0.001) and HOMA-IR (-0.68, 95% CI -0.98 to -0.37, p < 0.001) showed significant decreases in iron depletion group at end of study. Significant decrease in the numbers of hypoglycemic medicines in iron depletion group was shown at end of study (p < 0.001);66.7% of iron depletion group patients were receiving 1 or 2 medicines at end of studyversus none of the control group. Diastolic blood pressure (DBP), triglycerides and LDL-C decreased significantly while HDL-C levels showed significant rise after iron depletion. It can be concluded from the present study that iron depletion therapy is beneficial for improving the efficiency of glycemic control, DBP, and dyslipidemia in poorly controlled type 2 diabetics with iron over load.
文摘Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as thirdline chemotherapy. After two cycles of gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 wk), a partialtumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.
基金Supported by a grant from the Science Foundation of Xingtai City (No.20102025-2)
文摘Objective The aim of this study was to identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using laparoscopic surgery for the treatment of intramucosal poorly differentiated EGC.
文摘Objective： Patients with poorly controlled diabetes have more medical complications and are more difficult to manage. The objective of the present study was to evaluate the clinical outcomes of successful implementation of an employer initiated community pharmacist-based disease management program for diabetic patients with poorly controlled diabetes. Methods： Employees with poorly controlled diabetes （glycosylated hemoglobin （A1 C） level 〉 7.5%） were identified fi＇om a large diabetes disease management program, in a rural setting in Texas, US. A longitudinal retrospective study was conducted, analyzing clinical indicators in the diabetes patients following the community pharmacist-based disease management program. The program involved a comprehensive drug therapy assessment and individualized disease management education. Primary outcome measured in the present study was A1C levels, assessed at the baseline visit and at the end of the intervention. Results： A total of 64 patients with poorly controlled diabetes were identified. Significant improvement in mean clinical outcome scores was achieved for A1C levels （p = 0.0011）. At the end of the 1 year longitudinal intervention, targeted body mass index and A1C goals were attained by 35.9% （p 〈 0.001） and 15.6% patients, respectively. The 10 patients reaching goal levels post intervention were in the group that had baseline A1C of 7.5 to 9%. However, patients with 〉 9% A1C levels at baseline had a significant reduction （mean 2.1, p 〈 0.001） post intervention. Conclusion： The community pharmacist-based diabetes disease management program improved A1C levels of patients with poorly controlled diabetes.
基金National Natural Science Foundation of China(Nos.82073782 and 82241002).
文摘About 40%of approved drugs and nearly 90%of drug candidates are poorly water-soluble drugs.Low solubility reduces the drugability.Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application.This review briefly introduces the conventional solubilization techniques such as solubili-zers,hydrotropes,cosolvents,prodrugs,salt modification,micronization,cyclodextrin inclusion,solid dispersions,and details the crystallization strategies,ionic liquids,and polymer-based,lipid-based,and inorganic-based carriers in improving solubility and bioavailability.Some of the most commonly used approved carrier materials for solubilization techniques are presented.Several approved poorly water-soluble drugs using solubilization techniques are summarized.Furthermore,this review summa-rizes the solubilization mechanism of each solubilization technique,reviews the latest research advances and challenges,and evaluates the potential for clinical translation.This review could guide the selection of a solubilization approach,dosage form,and administration route for poorly water-soluble drugs.Moreover,we discuss several promising solubilization techniques attracting increasing attention worldwide.
文摘BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.
文摘Aluminum hydroxide adjuvant exhibits a poorly crystalline boehmite(PCB)structure,which demonstrates instability during prolonged storage.In the present study,we systematically investigated the quality alterations of the adjuvant stored at roo m temperature by analyzing its crystal structure,particle size distribution,electron microscopic characteristics,pH,isoelectric point(pI),and adsorption capacity.These assessments aimed to ensure the effectiveness and safety of vaccine production.Three batches of adjuvants were stored at room temperature for 15 months,and their changes were monitored using X-ray diffraction patterns,transmission electron microscopy(TEM),pH measurements,pI determination,and adsorption capacity analysis.X-ray diffraction revealed that the crystalline phases of aluminum hydroxide initially exhibited a PCB structure,which became progressively more ordered during storage.Notably,after 12 months,a new diffraction peak emerged at 18.2°2θ,with its intensity increasing over time.This corresponded to the formation of highly crystalline gibbsite and bayerite,which compromised the stability of the adjuvant.Furthermore,the pH and pI values decreased during storage,reflecting a decline in the chemical stability of the adjuvant.Comprising nanoparticles with a mean diameter of 130 nm,the adjuvant maintained a high surface area and excellent adsorption capacity.The adsorption rate at 8 mg BSA/mg Al3+consistently exceeded 97%,with no statistically significant differences observed between the adsorption capacities at 1 and 15 months(P>0.05).This indicated that the nanoparticle aluminum hydroxide adjuvant sustained high adsorption efficiency throughout the storage period,underscoring its reliability as a vaccine adsorbent.However,in the later stages of storage,the emergence of highly crystalline gibbsite and bayerite,coupled with declines in pH and pI,negatively impacted the adjuvant’s stability.Based on these findings,we recommended that aluminum hydroxide adjuvants should not be stored at room temperature for longer than 12 months to preserve their quality and efficacy.
