Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma.

To compare intensity-modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II-IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II-IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well-balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3-year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco-regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4-4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related-skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP-IMRT combination for maximizing survival for patients with stage II-IVb NPC.

Impact of Laparoscopic Versus Open Hepatectomy on Perioperative Clinical Outcomes of Patients with Primary Hepatic Carcinoma.

OBJECTIVE: To compare the perioperative outcomes of patients with primary hepatic carcinoma treated with laparoscopic hepatectomy (LH) with those treated with open hepatectomy (OH). METHODS: From January 2010 to August 2014, 100 patients with primary hepatic carcinoma were randomly divided into the LH group and OH group respectively, 50 patients in each group. And the incision length, blood loss, operative time, postoperative liver function, anus exhaust time, complications, length of postoperative hospital stay, and cost measures were compared. RESULTS: LH could achieve shorter incision length, less blood loss, more rapid recovery in liver function and gastrointestinal function, and shorter postoperative hospital stay length compared with OH for primary hepatic carcinoma patients (all P<0.05). However, LH could not significantly shorten operative time, and reduce postoperative complications and hospitalization cost (all P>0.05). CONCLUSION: Compared with OH, LH could improve perioperative outcomes of primary hepatic carcinoma patients.

Influence of Photodynamic Therapy on Apoptosis and Invasion of Human Cholangiocarcinoma QBC939 Cell Line.

OBJECTIVE: To investigate the effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines. METHODS: In vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 µg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells. RESULTS: Exposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 µg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells. CONCLUSION: PDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.

Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.

This study was designed to explore the effects of exosomal miR-421 secreted by cancer-associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF-derived exos (CAF-exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR-421, sirtuin-3 (SIRT3), and hypoxia duciblefactors-1 alpha (HIF-1α) levels. Cell counting kit-8 (CCK-8), wound-healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual-luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR-421 and SIRT3. Chromatin immunoprecipitation (f)-verified H3K9Ac enrichment in the HIF-1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR-421 from CAFs on PC. CAFs and exos were successfully isolated. CAF-exo-treated PC cells highly expressed miR-421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR-421 increased the expression of SIRT3. SIRT3 is a target of miR-421, and inhibiting the expression of SIRT3 reversed the negative effects of miR-421 knockdown on PC cell. Knocking down miR-421 in CAF-exo inhibited the expression of HIF-1α in PC cells. Moreover, SIRT3-mediated HIF-1α expression by regulating H3K9Ac. HIF-1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR-421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR-421 attenuated CAF-exo induced tumor growth. Exosomal miR-421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF-1α axis. This study provided insights into the molecular mechanism of PC.

LINC00960 regulates cell proliferation and glycolysis in pancreatic cancer through the miR-326-3p/TUFT1/AKT-mTOR axis.

Pancreatic cancer (PC) is a common malignant cancer characterized by high mortality and poor prognosis. LINC00690 was involved in the occurrence and progression of PC, but the underlying mechanisms require further investigation. The goal of this study was to figure out how LINC00960 mediates glycolysis in PC. LINC00960, miR-326-3p, and Tuftelin 1 (TUFT1) expression levels were detected in PC cell lines. LINC00960 and TUFT1 expression levels were increased in PC cells when compared with normal pancreatic cells, whereas miR-326-3p expression levels were decreased. The expression levels of LINC00690 affected glycolysis in PC, and inhibition of LINC00960 inhibited tumor growth in vivo. LINC00690 targeted and suppressed the expression of miR-326-3p. MiR-326-3p bound to TUFT1, and miR-326-3p inhibited AKT-mTOR pathway activation via TUFT1. In conclusion, the depletion of LINC00960 repressed cell proliferation and glycolysis in PC by mediating the miR-326-3p/TUFT1/AKT-mTOR axis. Thus, we present a novel mechanism underlying the progression of PC that suggests LINC00960 is a potential therapeutic target for this cancer.

[Evaluation on short term after hepatectomy for the patients with primary hepatocellular carcinoma].

OBJECTIVE: To analyze the high risk factors for tumor recurrence in short term after hepatectomy for the patients with primary hepatocellular carcinoma (HCC). METHODS: Five hundreds and two patients with primary HCC underwent hepatectomy were included from January 1997 to December 2008. Among these patients, males were 419 cases and females were 83 cases. The age was 14 to 82 years (average age 54 years). The results of evaluation on 2 months after resection and tumor recurrence and survival were analyzed. RESULTS: According to the operative and pathologic findings and the evaluation on 2 months after hepatectomy, the patients with vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher after resection or(and) positive TACE (tumor dyeing on TACE within 1 month and a deposit of lipiodol on CT scan) were high risk factors (high-risk group, 106 cases, 21.1%), the recurrence-free survival was 22%, 9% and 3% (1, 2 and 5 year) and overall survival was 52%, 25% and 8%. On the non-high risk group patients, the recurrence-free survival was 84%, 67%, 42% and 31% (1, 2, and 5 year) and overall survival was 97%, 85%, 56% and 35%. The bigger tumor, poor differentiation, tumor invading to liver capsule, satellite focus and TNM III-IV stage in high-risk groups were more significantly than that in non-high-risk groups. CONCLUSION: The vascular invasion, palliation resection, cutting edge pathologic residual tumor, lymph notes metastasis, serum AFP level continuing higher or (and) positive TACE within 2 months after resection are high risk factors for HCC patients in short term after hepatectomy, which mean tumor remnant.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.

Importance: The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective: To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants: Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions: The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures: The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results: Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance: In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02111460.

Laparoscopic splenectomy for littoral cell angioma of the spleen: A case report.

RATIONALE: Littoral cell angioma (LCA) is a rare primary vascular neoplasm of the spleen. It can be benign or malignant. Pathology and immunohistochemistry are the gold standards for the diagnosis of LCA. Therefore, splenectomy is recommended for the purpose of diagnosis and treatment, and subsequent follow-up is necessary. There are limited reports about LCA. Here, we present a case of a female patient with LCA undergoing laparoscopic splenectomy in order to provide clinical experience in LCA treatment. PATIENT CONCERNS: A 32-year-old female attended the outpatient Department of Hepatobiliary Surgery for follow-up of hepatic hemangiomas. The patient presented with intermittent abdominal distension, which was slightly under no obvious inducement. DIAGNOSIS: Physical examination found no signs of abdominal tenderness and rebound tenderness, and liver and spleen were impalpable. The contrast-enhanced computed tomography (CT) showed multiple space-occupying lesions in the spleen, mottled low-density lesions, multiple hypoattenuating nodules with no contrast enhancement on the arterious phase. Delayed contrast-enhanced helical CT scan displayed incomplete filling of hypodense splenic lesions. INTERVENTIONS: Given that it was uncertain whether it was a benign or a malignant tumor, a laparoscopic total splenectomy was performed. OUTCOMES: The final pathological diagnosis was LCA. Her postsurgical course was uneventful, and no surgery-related complications were found. No signs of recurrence were observed in the 16 months after the operation. LESSONS: LCA was a rare primary vascular neoplasm of the spleen, and laparoscopic splenectomy for LCA was safe and feasible, and postoperative course was uneventful. However, regular follow-up and long-time monitoring after splenectomy for LCA is recommended because of its potential malignant biological behavior.

A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal Carcinoma Patients at High Risk of Metastasis for Additional Induction Chemotherapy.

Purpose: Metastasis is one of the most important causes of treatment failure in nasopharyngeal carcinoma (NPC). In T4 or N2-3 patients at high-risk of metastasis, concurrent chemoradiotherapy (CCRT) is inadequate and additional induction chemotherapy (IC) is controversial. There is a critical need to develop a better patient stratification to efficiently identify patients at high-risk of metastasis for additional IC. Recently, Sequestosome 1 (SQSTM1)/p62, an autophagy adaptor protein, was identified as one of the metastasis-related proteins in NPC. However, the mechanism by which SQSTM1 is involved in NPC metastasis was not investigated.Experimental Design: The effect of SQSTM1 on cell migration and invasion was examined in vitro and in vivo SQSTM1 expression was analyzed in clinical NPC samples using IHC. Luciferase reporter analyses were conducted to identify the effects of SQSTM1 on NF-κB transcriptional activity. A prediction bio-model was constructed by Cox analysis. Retrospective and prospective randomized clinical data were adopted to build and test the model, respectively.Results: SQSTM1 mediated epithelial to mesenchymal transition (EMT) through the NF-κB pathway to promote NPC metastasis. Inhibiting SQSTM1 enhanced sensitivity to cisplatin in NPC cells. In NPC patients, high SQSTM1 expression was associated with increased risk of distant metastasis. Furthermore, we propose a prognostic bio-model based on SQSTM1 and N-stage to predict NPC metastasis. Most importantly, our prospective randomized study suggested that IC is beneficial for NPC patients with high metastasis risk.Conclusions: The prognostic bio-model identifies NPC patients at high-risk of metastasis for additional IC. Clin Cancer Res; 24(3); 648-58. ©2017 AACR.

Beneficial effects of anti-EGFR agents, Cetuximab or Nimotuzumab, in combination with concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) plus Cetuximab (CTX) or Nimotuzumab (NTZ) compared to those receiving induction chemotherapy (IC) plus CCRT. MATERIALS AND METHODS: From January 2008 to December 2013, 715 eligible patients were enrolled in the study. Using propensity scores to adjust for gender, age, Karnofsky performance status (KPS), tumor stage, node stage, and clinical stage, a well-balanced cohort was created by matching each patient who received CTX/NTZ plus CCRT (137 patients) with two patients who underwent IC plus CCRT (274 patients). The primary endpoint was overall survival (OS), and other outcome variables included disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional relapse-free survival (LRRFS). RESULTS AND CONCLUSION: The median follow-up was 57.0 months and 55.0 months for the CTX/NTZ plus CCRT group and IC plus CCRT group, respectively. No significant differences were found between the CTX/NTZ plus CCRT group and the IC plus CCRT group in 3-year OS (95.5% vs. 94.7%, P = 0.083), 3-year DFS (93.3% vs. 86.1%, P = 0.104), 3-year DMFS (96.2% vs. 92.5%, P = 0.243) and 3-year LRRFS (97.0% vs. 95.1%, P = 0.297). Patients undergoing IC plus CCRT suffered from severe hematologic toxicity and diarrhea compared with those treated with CTX/NTZ plus CCRT. The combination of CTX/NTZ with CCRT is comparable to IC plus CCRT treatment in survival outcomes for locoregionally advanced NPC patients but has a better safety profile than IC plus CCRT treatment.

Analogues of xanthones--Chalcones and bis-chalcones as α-glucosidase inhibitors and anti-diabetes candidates.

Two series of compounds (chalcones and bis-chalcones) were designed, synthesized, and evaluated as α-glucosidase inhibitors (AGIs) with 1-deoxynojirimycin as positive control in vitro. Most of the compounds with two or four hydroxyl groups showed better inhibitory activities than 1-deoxynojirimycin towards α-glucosidase with noncompetitive mechanism. Moreover, most of the hydroxy bis-chalcones exhibit good α-glucosidase inhibitory activities in enzyme test. Inspiringly, bis-chalcones 2g (at 1 µM concentration) has stronger effect than 1-deoxynojirimycin on reducing the glucose level in HepG-2 cells (human liver cancer cell line).

Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up.

We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was created by matching each patient who received CTX or NTZ plus CCRT with no more than four patients who received CCRT alone (1:4). Efficacy and safety were compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone, treatment with CTX/NTZ plus CCRT was associated with a significantly increased overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis-free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX related-skin reaction and mucositis was observed in the CTX plus CCRT arm. Multivariate analysis demonstrated the combination of CTX/NTZ was a significant protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our analysis suggests that the addition of CTX/NTZ to CCRT is more effective for maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.

Treatment of early duodenal fistula after orthotopic liver transplantation: a case report.

Gastrointestinal fistula as a serious complication could lead to imbalance of nutrition or death. Duodenal fistula after orthotopic liver transplantation is rare and its treatment is complicated. On April 28, 200, we performed orthotopic liver transplantation for a patient at our hospital. Eight days after operation duodenal fistula developed, but cured after 13-day treatment.