Effect of Pelvic Bone Marrow Sparing Intensity Modulated Radiation Therapy on Acute Hematologic Toxicity in Rectal Cancer Patients Undergoing Chemo-Radiotherapy.

BACKGROUND: While chemo-radiotherapy improves local control in patients with locally advanced rectal cancer, it can also increase acute hematological toxicity (HT), which leads to poor outcomes. Patients receiving bone marrow radiation have been shown to develop acute HT. However, the safety and efficacy of bone marrow sparing is undetermined. The aim of our study was to explore the feasible dosimetric constraints for pelvic bone marrow (PBM) that can be widely used in rectal cancer patients undergoing chemo-radiotherapy. METHODS: 112 rectal cancer patients were selected and divided into the PBM sparing IMRT group (60 cases) and the non-PBM sparing IMRT group (52 cases). All patients underwent pelvic radiotherapy with concurrent capecitabine-based chemotherapy. The PBM dosimetric constraints in the PBM sparing IMRT group were set to:V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%. An independent sample t test was applied for the dose-volume parameters, and Chi-squared analysis was applied for clinical parameters and adverse events. RESULTS: The radiation dose to PBM (V5~V45, Dmean, P<0.05), PBM sub-regions (V10~V35, Dmean, P<0.05) and both femoral heads (V5~V40, Dmean, P<0.05) decreased significantly in the PBM sparing IMRT group compared with that of the non-PBM sparing IMRT group (P<0.05). There was no significant difference in any dose-volume parameters of the bladder and small bowel in either groups, and none in the planning target volume (PTV) dose homogeneity and conformity (P>0.05). For acute HT observation, the incidence of grade 3 acute HT (χ2 = 7.094, P=0.008) was significantly reduced in patients treated with PBM sparing IMRT compared with patients treated with non-PBM sparing IMRT. There was no statistical difference in the incidence of vomiting, diarrhea, fatigue, anorexia, nausea, hand-foot syndrome, cystitis, perianal pain and perianal dermatitis in patients of both groups (P >0.05). CONCLUSIONS: Applying PBM dosimetric constraints (V10 ≤ 85%, V20 ≤ 65% and V30 ≤ 45%) can significantly reduce the radiation dose to PBM. The patients treated with PBM sparing IMRT had a lower incidence of acute HT compared with those treated with non-PBM sparing IMRT. Applying the PBM dosimetric constraints proposed by our study can benefits the patients with rectal cancer undergoing capecitabine-based chemo-radiotherapy.

A comprehensive and clinical-oriented evaluation criteria based on DVH information and gamma passing rates analysis for IMRT plan 3D verification.

PURPOSE: To accomplish the 3D dose verification to IMRT plan by incorporating DVH information and gamma passing rates (GPs) (DVH_GPs) so as to better correlate the patient-specific quality assurance (QA) results with clinically relevant metrics. MATERIALS AND METHODS: DVH_GPs analysis was performed to specific structures of 51 intensity-modulated radiotherapy (IMRT) treatment plans (17 plans each for oropharyngeal neoplasm, esophageal neoplasm, and cervical neoplasm) with Delta4 3D dose verification system. Based on the DVH action levels of 5% and GPs action levels of 90% (3%/2 mm), the evaluation results of DVH_GPs analysis were categorized into four regions as follows: the true positive (TP) (%DE> 5%, GPs < 90%), the false positive (FP) (%DE ≤ 5%, GPs < 90%), the false negative (FN) (%DE> 5%, GPs ≥ 90%), and the true negative (TN) (%DE ≤ 5%, GPs ≥ 90%). Considering the actual situation, the final patient-specific QA determination was made based on the DVH_GPs evaluation results. In order to exclude the impact of Delta4 phantom on the DVH_GPs evaluation results, 5 cm phantom shift verification was carried out to structures with abnormal results (femoral heads, lung, heart). RESULTS: In DVH_GPs evaluation, 58 cases with FN, 5 cases with FP, and 2 cases with TP were observed. After the phantom shift verification, the extremely abnormal FN of both lung (%DE = 21.52%±8.20%) and heart (%DE = 19.76%) in the oropharyngeal neoplasm plans and of the bilateral formal heads (%DE = 26.41%±13.45%) in cervical neoplasm plans disappeared dramatically. DVH_GPs analysis was performed to all evaluation results in combination with clinical treatment criteria. Finally, only one TP case from the oropharyngeal neoplasm plans and one FN case from the esophageal neoplasm plans did not meet the treatment requirements, so they needed to be replanned. CONCLUSION: The proposed DVH_GPs evaluation method first make up the deficiency of conventional gamma analysis regarding intensity information and space information. Moreover, it improves the correlation between the patient-specific QA results and clinically relevant metrics. Finally, it can distinguish the TP, TN, FP, and FN in the evaluation results. They are affected by many factors such as the action levels of DVH and GPs, the feature of the specific structure, the QA device, etc. Therefore, medical physicist should make final patient-specific QA decision not only by taking into account the information of DVH and GPs, but also the practical situation.

Appleby operation for carcinoma of the body and tail of the pancreas.

AIMS: The aim of this study is to evaluate the therapeutic efficacy of Appleby operation for carcinoma of the body and tail of pancreas. MATERIALS AND METHODS: From March 2010 to February 2015, Appleby operation was performed in 17 patients with carcinoma of the body and tail of pancreas. The values of fasting plasma blood, body weight (BW), visual analog pain intensity scale (VAS score), and the quality of life indices were evaluated before and 1 day, 1, 2, 6 weeks after surgery. Survival time, tumor recurrence time, hospitalization time, and treatment-related complications were analyzed. RESULTS: There was no hospital mortality. Pancreatic fistula and diarrhea were major and most frequent. The rate of morbidity in general was 47.1%. After operation, all of the patients were completely pain-free. The VAS score decreased more after surgery comparing with before (83.2 ± 8.5 vs. 1.9 ± 3.6, P < 0.05). After operation, patients gained more than their preoperative BW with a mean increment of (4.1 ± 1.3 kg) (68.1 ± 4.3 vs. 64.0 ± 6.7, P < 0.05). A significant rise of the overall quality of life index was observed after surgery (93.8 ± 9.7 vs. 68.6 ± 6.7, P < 0.05). The 1-, 2-, 3-, and 5-year recurrence rates were 22.9%, 58.9%, 72.6%, and 72.6%, respectively. The 1-, 2-, 3-, and 5-year survival rates after operation were 80.4%, 54.2%, 32.5%, and 16.3%, respectively. CONCLUSIONS: Appleby operation is both safe and effective with regard to pain relief and improvement of overall quality of life. Appleby operation can also achieve a high survival rate and a long overall survival time.

Design of amphiphilic PCL-PEG-PCL block copolymers as vehicles of Ginkgolide B and their brain-targeting studies.

The amphiphilic PEG-b-PCL block copolymers were synthesized by ring-opening polymerization. The specific and selective antagonists of platelet activating factor, Ginkgolide B (GB), was successfully encapsulated in the synthesized PEG-PCL nanoparticles (NPs) with high Encapsulation Efficiency and Drug Loading. The synthesis of different PEG-PCL copolymers were confirmed with FTIR and 1H NMR spectra. The morphology and particles size distribution of cargo-free PEG-PCL NPs were studied by transmission electron microscope (TEM) analysis and Malvern laser particle analyzer. The bio-distribution and pharmacodynamics studies of GB were studied with Wistar mice as the animal models via tail injecting of GB-PEG-PCL NPs. Results from Malvern laser particle analyzer and TEM analysis illustrated that the cargo-free NPs showed narrow distribution and well separated particles size of about 60 nm in diameter. The in vitro experiment of GB-PEG-PCL NPs exhibited an extended release behavior. The bio-distribution data suggested that Tween-80 covered GB-PEG-PCL NPs showed a brain-targeting behavior. The pharmacodynamics results confirmed that the GB-PEG-PCL NPs had an obvious cerebral protection effect.

Decreased levels of miR-34a and miR-217 act as predictor biomarkers of aggressive progression and poor prognosis in hepatocellular carcinoma.

BACKGROUND: MicroRNAs (miRNAs) play key roles in tumor development and progression. The aim of this study was to explore the expression levels of miR-34a and miR-217 in hepatocellular carcinoma (HCC) and to further investigate the clinicopathological and prognostic value of miR-34a and miR-217. METHODS: The expression levels of miR-34a and miR-217 were evaluated using quantitative real-time PCR (qRT-PCR). Associations between these miRNAs expression and clinicopathological features were analyzed. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. RESULTS: We found that miR-34a expression was significantly downregulated in HCC tissues (P<0.05). Reduced expression of miR-34a was associated with vascular invasion, and advanced TNM stage (P<0.05). Kaplan-Meier revealed that reduced expression of miR-34a was associated with poor overall survival (log-rank test, P<0.05). We found that miR-217 was downregulated in HCC tissues. Decreased expression of miR-217 was remarkably correlated vascular invasion, and advanced TNM stage (P<0.05). Kaplan-Meier analysis and log-rank test showed that HCC patients with low expression of miR-217 was associated with shorter overall survival than patients with high expression (log-rank test, P<0.05). CONCLUSIONS: Our data showed that downregulation of miR-34a and miR-217 was associated with HCC progression and both of them may act as tumor suppressor in HCC.

SENP2 regulated the stability of ß-catenin through WWOX in hepatocellular carcinoma cell.

SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. SENP2 has been reported to play a critical role in the control of hepatocellular carcinoma (HCC) cell growth by modulating the stability of ß-catenin. However, the underlying mechanism remains largely unknown. Here, we show that the WW domain-containing oxidoreductase (WWOX), a novel inhibitor of the Wnt/ß-catenin pathway, is required for stabilization of ß-catenin regulated by SENP2 in HCC cells. The transcriptional level of WWOX is tightly regulated by SENP2. Moreover, knockdown of WWOX by siRNA attuned SENP2-induced ß-catenin degradation and decreased SENP2-mediated HCC cell proliferation arrest. Taken together, our data suggested that WWOX is a key downstream modulator of the SENP2 tumor suppressor function in HCC cell.

Clinical and pathological features and surgical treatment of Budd-Chiari syndrome-associated hepatocellular carcinoma.

BACKGROUND: Budd-Chiari syndrome (BCS) is characterized by liver sinusoidal congestion, ischemic liver cell damage, and liver portal hypertension caused by hepatic venous outflow constriction. The aim of this research was to investigate the clinicopathological features of BCS-associated hepatocellular carcinoma (HCC) and explore its surgical treatment and prognosis. METHODS: Clinical data from 38 patients with BCS-associated HCC who were surgically treated in our hospital from July 1998 to August 2010 were retrospectively analyzed. The clinicopathological features and prognosis of patients with BCSassociated HCC and surgical treatment for BCS-associated HCC were investigated. RESULTS: Compared to the patients with hepatitis B virus (HBV)-associated HCC, the patients with BCS-associated HCC showed a female predominance, and had significantly higher cirrhosis rate, higher incidence of solitary tumors, lower incidence of infiltrative growth, higher proportion of marginal or exogenous growth, lower rate of portal vein invasion, and higher degree of differentiation. Median survival was longer in patients with BCS-associated HCC (76 months) than in those with HBV associated HCC (38 months). Of 38 patients with BCS-associated HCC, 22 patients who received combined surgery mainly by liver resection plus cavoatrial shunts exhibited hepatic venous outflow constriction relief, while the other 16 patients only underwent liver resection. The combined surgery group had significantly longer survival and lower incidences of post-operative lethal complications (P < 0.05). Multivariate analysis showed that relief of hepatic venous outflow obstruction was a protective factor for survival of patients with BCS-associated HCC, whereas portal vein invasion was a risk factor. CONCLUSIONS: BCS-associated HCC has a more favorable biological behavior and prognosis than HBV-associated HCC. For patients with BCS-associated HCC, tumor resection accompanied with relief of hepatic venous outflow obstruction can reduce the incidence of complications and extend survival.

Surgical operation and re-operation for hepatocellular carcinoma with bile duct thrombosis.

BACKGROUND: Few reports have evaluated the efficacy of re-operation for relapse after initial surgery for hepatocellular carcinoma (HCC) with bile duct thrombosis (BDT). The aim of this study was to investigate the efficacy of initial surgery and subsequent re-operation for HCC with BDT, and their effects on prognosis. METHODS: The clinical data of 880 patients with HCC, including 28 patients with BDT, who underwent radical hepatectomy between 1998 and 2008 in our hospital, were reviewed. The effects of BDT and re-operation on prognosis were retrospectively analyzed. RESULTS: The 1-, 3- and 5-year survival rates were 89.3%, 46.4% and 21.4%, respectively, in 28 patients with BDT versus 91.4%, 52.9% and 20.9% in 852 patients without BDT (P>0.05). Six patients with BDT underwent re-operation after disease relapse, and their survival time was significantly longer than those who did not undergo re-operation (P<0.05). Multivariate analysis indicated that portal vein invasion and tumor size were independently associated with tumor relapse and prognosis (P<0.05). Univariate analysis and multivariate analyses showed that obstructive jaundice was not significantly correlated with tumor relapse or prognosis (P>0.05). CONCLUSIONS: Hepatectomy plus BDT removal is an effective treatment option for HCC with BDT. Obstructive jaundice is not a contraindication for surgery. Re-operation after relapse can provide good outcomes if the cases are appropriately selected.

[Duodenum-preserving pancreatic head resection in treating patients with chronic pancreatitis].

OBJECTIVE: To evaluate the therapeutic efficacy of duodenum-preserving pancreatic head resection (DPPHR) for severe chronic pancreatitis (CP). METHODS: From February 2004 to March 2010, duodenum-preserving resection of pancreatic head was performed in 21 patients with severe CP. A "modified-DPPHR" was carried out in 14 patients of them and a "Frey's DPPHR" in the other 7 patients. The values of fasting plasma blood (FPB), oral glucose tolerance test (OGTT), body weight (BW), visual analogue pain intensity scale (VAS score) and the quality of life indices were evaluated before and 6(th) month after surgery. RESULTS: There was no hospital mortality. The complications from adjacent organs were resolved definitively. Pancreatic fistula was the major and the most frequent morbidity occurring in 23.8% of the patients. After operation 85.7% of the patients were completely pain-free and 14.3% had continuing abdominal pain. The VAS score decreased more after surgery comparing with before and there was a significant difference (81.1 ± 5.6 vs 7.8 ± 3.6, P < 0.05). The value of FPB in post-operative patients was similar to that in pre-operative ones and there was no significant difference [(5.3 ± 0.4) mmol/L vs (5.4 ± 0.4) mmol/L, P > 0.05]. The value of 2 h-OGGT in post-operative patients was also similar to that in pre-operative ones and it did not differ significantly [(8.0 ± 0.6) mmol/L vs (7.9 ± 0.6) mmol/L, P > 0.05]. After operation 77.8% of patients gained more than 5% of their pre-operative body weight with a mean increment of (4.8 ± 0.7) kg (58.8 ± 1.8 vs 53.9 ± 2.0, P < 0.05). A significant rise of the overall quality of life index was observed after surgery (78.1 ± 7.3 vs 61.0 ± 6.2, P < 0.05). CONCLUSION: DPPHR is both safe and effective with regard to pain relief, a definitive control of complications affecting adjacent organs and an improvement of overall quality of life. It leads to no further deterioration of pancreatic functions.

[Volumetric and geometric changes of parotids occurring during IMRT for nasopharyngeal carcinoma (NPC) using daily CBCT].

OBJECTIVE: To study the volumetric and geometric changes of parotids occurring during IMRT treatment for NPC. METHODS: The pre-treatment CBCT images of 10 patients were obtained using kV-CBCT and transmitted back to TPS. The gross tumor volumes (GTVs) and volumes of parotids were manually drawn slice by slice on the CBCT images by the same person using image analysis software system Tomcon 3.0. For position changes, the center-of-mass (COM) were calculated using Pinnacle 8.0 software. Then the distance from the parotid to the atlas was assessed. RESULTS: The volumetric changes of GTVs and parotids were correlated with the days of treatment. The volumes of GTVs decreased with a mean total loss of 9.85 cm3 (5.10-21.40 cm3) and a median change rate of 0.20 cm3/d (0.10-0.46 cm3/d). The volumes of left parotids decreased with a median total loss of 5.70 cm3 (3.20-12.00 cm3) and a median change rate of 0.13 cm3/d (0.07-0.27 cm3/d). The volumes of right parotids decreased with a median total loss of 8.05 cm3 (3.00-13.40 cm3) and a median change rate of 0.18 cm3/d (0.06-0.29 cm3/d). The distance between the left parotid and the atlas decreased with a median total loss of 3.45 mm (0.70-7.60 mm) and a median change rate of 0.07 mm/d (0.01-0.11 mm/d). The distance between the right parotids and the atlas decreased with a median total loss of 2.60 mm (1.50-4.40 mm) and a median change rate of 0.05 mm/d (0.03-0.12 mm/d). CONCLUSION: Significant reductions of GTVs occur after the third or forth week of IMRT treatment for NPC, which indicates that a second plan of CT scanning or treatment replanning might be necessary after 3-4 weeks of treatment to minimize radiations to vital organs.

[Treatment of Budd-Chiari syndrome with occlusion of both inferior vena cava and hepatic veins lesions by interposition of graft meso-caval-atrial shunt].

OBJECTIVE: To evaluate the therapeutic efficacy of interposition of graft meso-cavo-atri shunt (MCAS) for the treatment of Budd-Chiari syndrome (BCS) with occlusion of both inferior cava vena (ICV) and hepatic veins (HVs). METHODS: 51 BCS patients with combined occlusion of ICV and HVs, 30 males and 20 females, aged 18-45, underwent MCAS. A 16-18 mm ring-reinforced graft (main graft) was anastomosed firstly to the side of ICV with continuous 5/0 vascular suture, then to the side of the right atrium with continuous 5/0 vascular suture. A 10-12 mm graft (secondary graft) was anastomosed to the side of the superior mesenteric vein (SMV) with continuous 5/0 vascular suture, then to the side of the main graft with continuous 5/0 vascular suture. The pressure and blood flow of ICV and portal vein (PV) were examined before and after operation. The patients were followed up for 6 months to 16 years. RESULTS: There was no perioperative death. During the follow-up no thrombosis of the main graft was found but thrombosis of the secondary graft occurred in two cases. The patency rates of the main and secondary grafts were 100% and 96.1% respectively. The total patency rate of graft was 96.1%. After operation the pressure of IVC and PV decreased by 17.4 +/- 5.7 cm HO2O and 17.0 +/- 7.0 cm H2O respectively compared with those before operation. CONCLUSION: MCAS is very effective in decompression of PC and IVC. MCAS may be a valuable surgical procedure for treatment of BCS with occlusion of both ICV and HVs.

[Preparation of 10-hydroxycamptothecin semisolid lipid nanoparticles and investigation of its stability].

OBJECTIVE: To prepare 10-hydroxycamptothecin-semisolid lipid nanoparticles (HCPT-SSLN) and investigate its stability. METHODS: HCPT-SSLN was prepared by the method of "emulsion evaporation at a high temperature and solidification at a low temperature"; The morphology was examined by transmission electron microscope; The particle size and xi potential were determined by laser granularity equipment; The physical stability of both suspl and freeze drying powder of HCPT-SSLN were investigated. RESULTS: The mean particle size of the prepared HCPT-SSLN was 130.5 nm, drug loading was 2.51%, entrapment efficiency was 79.19%, xi potential was -33.1 mV; Placed at room temperature and 4 degrees C for 6 months, the appearance, particle size and entrapment efficiency of HCPT-SSLN were all stable. Moreover, the freeze drying powder was more stable than the suspl. CONCLUSION: The HCPT-SSLN has high entrapment efficiency and drug loading, uniform particle size, good stability, which initially indicates that HCPT is fit for being incorporated into SSLN.

[Preparation and surface modification of the magnetic fluid as a targeted drug carrier].

Magnetic fluid containing Fe(3)O(4) as mother nucleus was prepared by chemical coprecipitation and treated with dextran-70 for surface modification. The dextran-70-modified magnetic fluid was reacted with 6-bromohexanoic acid and their chemical stability was studied, with the structure characterized by using laser granulometer, X-ray diffraction, Fourier-transform infrared analysis and transmission electron microscopy. The results showed that the magnetic fluid with surface modification by dextran-70 exhibited high stability in the presence strong alkali or acid. No chemical changes occurred in the magnetic Fe(3)O(4) nucleus surrounded by alkali-treated dextran-70 and the organic chain linked to the surface dextran rendered the reaction to the anti-cancer drug such as mitomycin C possible, suggesting the potential of the preparation as a drug carrier.