Objective: To compare the safety and effectiveness of esophagojejunostomy (EJS) through extracorporeal and intracorporeal methods after laparoscopic total gastrectomy (LTG). Methods: A retrospective cohort study was carried out. Clinicopathological data of 261 gastric cancer patients who underwent LTG, D2 lymphadenectomy, and Roux-en-Y EJS with complete postoperative 6-month follow-up data at the General Surgery Department of Nanfang Hospital from October 2018 to June 2021 were collected. Among these 261 patients, 139 underwent EJS with a circular stapler via mini-laparotomy (extracorporeal group), while 122 underwent intracorporeal EJS (intracorporeal group), including 43 with OrVil(TM) anastomosis (OrVil(TM) subgroup) and 79 with Overlap anastomosis (Overlap subgroup). Compared with the extracorporeal group, the intracorporeal group had higher body mass index, smaller tumor size, earlier T stage and M stage (all P<0.05). Compared with the Overlap subgroup, the Orvil(TM) subgroup had higher proportions of upper gastrointestinal obstruction and esophagus involvement, and more advanced T stage (all P<0.05). No other significant differences in the baseline data were found (all P>0.05). The primary outcome was complications at postoperative 6-month. The secondary outcomes were operative status, intraoperative complication and postoperative recovery. Continuous variables with a skewed distribution are expressed as the median (interquartile range), and were compared using Mann-Whitney U test. Categorical variables are expressed as the number and percentage and were compared with the Pearson chi-square, continuity correction or Fisher's exact test. Results: Compared with the extracorporeal group, the intracorporeal group had smaller incision [5.0 (1.0) cm vs. 8.0 (1.0) cm, Z=-10.931, P=0.001], lower rate of combined organ resection [0.8% (1/122) vs. 7.9% (11/139), χ(2)=7.454, P=0.006] and higher rate of R0 resection [94.3% (115/122) vs. 84.9 (118/139), χ(2)=5.957, P=0.015]. The morbidity of intraoperative complication in the extracorporeal group and intracorporeal group was 2.9% (4/139) and 4.1% (5/122), respectively (χ(2)=0.040, P=0.842). In terms of postoperative recovery, the extracorporeal group had shorter time to liquid diet [(5.1±2.4) days vs. (5.9±3.6) days, t=-2.268, P=0.024] and soft diet [(7.3±3.7) days vs. (8.8±6.5) days, t=-2.227, P=0.027], and shorter postoperative hospital stay [(10.5±5.1) days vs. (12.2±7.7) days, t=-2.108, P=0.036]. The morbidity of postoperative complication within 6 months in the extracorporeal group and intracorporeal group was 25.9% (36/139) and 31.1%, (38/122) respectively (P=0.348). Furthermore, there was also no significant difference in the morbidity of postoperative EJS complications [extracorporeal group vs. intracorporeal group: 5.0% (7/139) vs. 82.% (10/122), P=0.302]. The severity of postoperative complications between the two groups was not statistically significant (P=0.289). In the intracorporeal group, the Orvil(TM) subgroup had more estimated blood loss [100.0 (100.0) ml vs.50.0 (50.0) ml, Z=-2.992, P=0.003] and larger incision [6.0 (1.0) cm vs. 5.0 (1.0) cm, Z=-3.428, P=0.001] than the Overlap subgroup, seemed to have higher morbidity of intraoperative complication [7.0% (3/43) vs. 2.5% (2/79),P=0.480] and postoperative complications [37.2% (16/43) vs. 27.8% (22/79), P=0.286], and more severe classification of complication (P=0.289). Conclusions: The intracorporeal EJS after LTG has similar safety to extracorporeal EJS. As for intracorporeal EJS, the Overlap method is safer and has more potential advantages than Orvil(TM) method, and is worthy of further exploration and optimization.
Anastomosis, Surgical/methods* ; Gastrectomy/methods* ; Humans ; Intraoperative Complications ; Laparoscopy/methods* ; Postoperative Complications/surgery* ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

PURPOSE: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. MATERIALS AND METHODS: In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary end-point was progress-free survival (PFS). RESULTS: The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the high-SAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. CONCLUSION: The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.
C-Reactive Protein* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Observational Study ; Prognosis ; Prospective Studies* ; Serum Amyloid A Protein* ; Survival Analysis

INTRODUCTIONPatients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients.

METHODSClinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS).

RESULTSUnivariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis.

CONCLUSIONWe identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Carcinoma ; Humans ; Lymphocyte Count ; Lymphocytes ; Monocytes ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; Prognosis ; ROC Curve

Introduction:Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients. Methods:Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS). Results:Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390 × 109/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665 × 109/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95%confidence interval [CI]=0.41–0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95%CI=0.64–0.93, P=0.007), and monocyte count (HR=1.98, 95%CI=1.63–2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis. Conclusion:We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Dose Fractionation ; Drug Chronotherapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; adverse effects ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Neutropenia ; chemically induced ; Radiotherapy, High-Energy ; Stomatitis ; etiology ; Survival Rate ; Young Adult

Postradiation nasopharyngeal necrosis is an important late effect of radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma. In the present study, we reviewed the clinical and imaging features of 67 patients with pathologically diagnosed postradiation nasopharyngeal necrosis who were treated at Sun Yat-sen University Cancer Center between June 2006 and January 2010. Their clinical manifestations, endoscopic findings, and imaging features were analyzed. Early nasopharyngeal necrosis was limited to a local site in the nasopharyngeal region, and the tissue defect was not obvious, whereas deep parapharyngeal ulcer or signs of osteoradionecrosis in the basilar region was observed in serious cases. Those with osteoradionecrosis and/or exposed carotid artery had a high mortality. In conclusion, Postradiation nasopharyngeal necrosis has characteristic magnetic resonance imaging appearances, which associate well with clinical findings, but pathologic examination is essential to make the diagnosis.
Adult ; Aged ; Carcinoma ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Nasopharynx ; pathology ; radiation effects ; Necrosis ; Osteoradionecrosis ; diagnosis ; etiology ; Radiation Injuries ; diagnosis ; etiology ; Radiotherapy, Intensity-Modulated ; adverse effects

BACKGROUNDInfantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.

METHODSStem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction (PCR), immunofluorescent staining and injection into BALB/c-nu mice.

RESULTSHemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC). Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days. After 1 - 2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P < 0.05).

CONCLUSIONSHemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.

AC133 Antigen ; Animals ; Antigens, CD ; analysis ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Collagen ; Disease Models, Animal ; Drug Combinations ; Glycoproteins ; analysis ; Hemangioma ; pathology ; Humans ; Laminin ; Male ; Mice ; Mice, Inbred BALB C ; Neoplastic Stem Cells ; chemistry ; pathology ; Peptides ; analysis ; Proteoglycans ; Vascular Endothelial Growth Factor A ; physiology

BACKGROUND/AIMS: To investigate the beneficial effect of N-Acetylcysteine (NAC) on pancreatic microvascular perfusion in acute necrotizing pancreatitis (ANP). METHODS: Fifty-four rats were divided into a control group, an ANP group and an NAC-treated group. The ANP model was established by a retrograde injection of 3% sodium taurocholate into the pancreatic duct. The NAC-treated group received an intravenous infusion of NAC just 2 hours before and 30 minutes after the induction of ANP. The pancreatic microvascular perfusion was measured with laser Doppler flowmetry and pancreatic samples were collected for histological examination. RESULTS: The microvascular perfusion in the NAC-treated group decreased slightly and exhibited a significant increase compared to the ANP group (p<0.01). A pathological examination revealed that edema and inflammatory infiltration decreased, and the hemorrhaging and necrosis of the pancreas were significantly reduced. CONCLUSIONS: NAC could improve pancreatic microvascular perfusion and alleviate the severity of sodium taurocholate-induced ANP, possibly representing a new therapeutic approach to prevent the progression of ANP.
Acetylcysteine ; Animals ; Atrial Natriuretic Factor ; Edema ; Infusions, Intravenous ; Laser-Doppler Flowmetry ; Microcirculation ; Necrosis ; Pancreas ; Pancreatic Ducts ; Pancreatitis, Acute Necrotizing ; Perfusion ; Rats ; Sodium ; Taurocholic Acid

Background Infantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck.Various treatment options including oral propranolol have been described for IH,but the mechanism of drugs remains enigmatic.The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.Methods Stem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads.Their phenotype and angiogenic property were investigated by flow cytometry,culturing on Matrigel,real-time polymerase chain reaction (PCR),immunofluorescent staining and injection into BALB/c-nu mice.Results HemSCs had robust ability of proliferating and cloning.The time of cells doubling in proliferative phase was 16 hours.Flow cytometry showed that HemSCs expressed mesenchymal markers CD29,CD44,but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45.The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC).Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs).After HemSCs were cultured on Matrigel in vitro,they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days.After 1-2 weeks of implantation into immunodeficient mice,HemSCs generated glucose transporter 1 positive blood vessels.When co-injected with HUVECs,the vascularization of HemSCs was greatly enhanced.However,the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P ＜0.05).Conclusions HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability,which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.

BACKGROUNDAttention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

METHODSThis 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

RESULTSA total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

CONCLUSIONThis open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Delayed-Action Preparations ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Prospective Studies ; Treatment Outcome