基于核磁共振的癌症非侵入式诊断理论与技术研究

分析了核磁共振技术在癌症临床诊断领域的应用现状、相关理论与技术的发展趋势,概述了对核磁共振设备产生的FID信号、MRI和MRS的数据分析技术,并以MRS为重点,研究了FID信号和波谱数据的特点,提出了利用小波变换和模式识别技术对FID信号和波谱数据进行分析的技术方案,并对信号的小波阈值去噪、小波基函数的选择、MRS特征识别与提取等问题进行了探索性研究,对核磁共振为基础的相关技术在癌症临床诊断领域内应用的进一步发展提示了方向。

Inhibition of lymphangiogenesis,nodal and lung metastasis by dihydroartemisinin in mice bearing Lewis lung carcinoma

Objective:To investigate the activity of anti-malarial dihydroartemisinin (DHA) on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma (LLC). Methods: The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups: control group, DHA group, DHA+ferrous sulfate (FS) group and FS group, with 25 mice in each group. Tumor volumes and weights, nodal and lung metastasis, and survival were monitored. Tumor lymphatic microvessel density (LMVD) was determined by lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) immnohistochemistry. After LLC cells were treated with DHA or DHA+FS, protein and mRNA levels of vascular endothelial growth factor (VEGF) -C were evaluated by Western blotting and real time quantitative RT-PCR, respectively. Results: Oral administration of DHA or DHA+FS inhibited lymph node and lung metastasis, and prolonged survival. However, no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions, but not in the intratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion: DHA effectively inhibits LLC transplantation tumor lymphangiogenesis, nodal and lung metastasis, and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.

Unsuspected Gallbladder Cancer During or After Laparoscopic Cholecystectomy

Objective To summarize the clinical features and outcomes of unsuspected gallbladder carcinoma （HGC） detected during or after laparoscopic cholecystectomy. Methods Medical records of 8005 patients, who underwent laparoscopic cholecystectomy in Peking Hnion Medical College Hospital between June 1993 and June 2011, were reviewed. Patients that pathologically diagnosed as HGC were retrospectively studied in terms of clinical features, preoperative and postoperative diagnosis, surviving period, and complications. Results In the 8005 patients who received laparoscopic cholecystectomy, 36 （0.45%） were diagnosed as LIGC during （25 patients） or after （11 patients） laparoscopic cholecystectomy. The gallbladder cancer was staged as T1 in 16 patients, T2 in 11 patients, and T3 in 9 patients. The 1-, 3-, and 5-year survival rates of all the patients were 88.9% （32/36）, 63.9% （23/36）, and 58.3% （21/36）. The 5-year survival rates in T1 stage, T2 stage, and T3 stage patients were 100%, 75.0%, and 0.0%, respectively. Conclusions The survival rate of HGC is associated with tumor stage, not with operation approaches. Laparoscopic cholecystectomy is appropriate for T 1 patients.

Factors influencing the presence of circulating differentiated thyroid cancer cells in the thyroidectomy perioperative period

Objective The aim of the study was to detect circulating differentiated thyroid cancer （DTC） micrometas-tasis and to investigate the factors influencing their presence in the perioperative thyroiclectomy period. Methods DTC micrometastases in the peripheral blood were detected with flow cytometry, and patient clinical and pathological factors were analyzed in 327 DTC patients. Results Circulating blood micrometastases were present in the peripheral circulation at a higher rate 1 week postoperatively than preoperatively and at 4 weeks postoperatively （P 〈 0.05）. The preoperative pres- ence of circulating micrometastasis was associated with the size of the tumor and the presence of lymph node metastasis （P 〈 0.05）, but was not related to the degree of tumor differentiation （P 〉 0.05）. At 4 weeks postoperatively, the presence of circulating micrometastasis was not associated with tumor size or lymph node stage （P 〉 0.05）, but was associated with poorly differentiated tumors （P 〈 0.05）. Conclusion The presence of circulating DTC micrometastases correlates to tumor size, lymph node stage, and operative manipulation. The differentiation degree of the tumors were associated with the persistent presence of micrometastasis in the circulating blood.

Systemic chemotherapy for metastatic breast cancer

Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer （MBC）. Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metasta- sis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combi- nation agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel- bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and catuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall sur- vival with maintenance chemotherapy according to a Korean phase III clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy （X-based X） appears favorable based on a series of domestic studies.

Abnormal expression of VEGF and its gene transcription status as diagnostic indicators in patients with non-small cell lung cancer

Objective Angiogenesis is known to be essential for the survival,growth,invasion,and metastasis of lung cancer cells. Vascular endothelial growth factor(VEGF) is an important factor regulating angiogenesis of non-small cell lung cancer(NSCLC); however,its pathologic features and significance are unclear. In this study,the tissue VEGF expression levels and its gene transcriptional status,as well as circulating VEGF levels,were investigated in patients with lung disease. Methods VEGF protein and m RNA expression levels in 38 lung tissue samples were analyzed by immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR),respectively. Circulating VEGF levels were detected quantitatively by an enzyme linked immuno-sorbent assay. Results The level of VEGF expression was significantly higher in lung cancer tissue than in the corresponding paracancerous or non-cancerous tissues. The average level of VEGF-positive staining was 76% in tissue samples from NSCLC patients; the levels were 89% in tissue samples from stage III patients and 92% in stage IV patients. High VEGF expression was also evident in cases with lymph node metastasis(84%),distant metastasis(90%),and lower differentiation degree(89%). VEGF m RNA in cancerous tissues was represented predominantly by the VEGF121 and VEGF165 isoforms. Circulating VEGF levels were significantly higher in NSCLC patients [(840 ± 324) pg/m L] than in patients with benign lung diseases [(308 ± 96) pg/m L] or in healthy individuals serving as controls [(252 ± 108) pg/m L]. Conclusion The over-expression of lung VEGF and its gene transcription status should be useful molecular indicators for NSCLC diagnosis.

Diagnosis and treatment of peripherally inserted central catheters(PICC)-related sepsis in breast cancer patients carrying PICC catheter for chemotherapy

Objective:The aim of our research was to study the incidence,clinical diagnosis and treatment of peripherally inserted central catheters(PICC)-related sepsis in breast cancer patients carrying PICC catheter for chemotherapy.Methods:The data of the incidence,diagnosis and treatment of PICC-related sepsis in 215 cases of breast cancer patients carrying PICC catheter for chemotherapy in our hospital from August,2009 to September,2011 were analyzed retrospectively.Results:216 PICCs had been successfully applied in 215 cases of breast cancer patients and followed for a total of 19,109 catheter days,(median catheterization duration,88.9 days,range 1-212 days).Among those,3(1.39%) PICCs were removed respectively as a result of PICC-related sepsis in 29,73 and 108 catheter-days(median 70 d),with a rate of 0.16 per 1000 catheter-days.Conclusion:Chemotherapeutic treatment via PICC for breast cancer patients is one of the most secure and effective measures but there exists small number of cases in which PICC catheter related sepsis is possible.Careful observation of relevant symptoms and signs,early diagnosis and treatment,not relying completely on blood culture tests and timely removal of PICC catheter can be very effective in treating PICC-related sepsis in these patients.

Improving patient care and accuracy of given doses in radiation therapy using in vivo dosimetry verification

Objective This work aims to verify and improve the dose given for cancer patients in radiation therapy by using diodes to enhance patient in vivo dosimetry on a routine basis. Some characteristics of two available semi-conductor diode dosimetry systems were evaluated. Methods The diodes had been calibrated to read the dose at Dmax below the surface. Correction factors of clinical relevance were quantified to convert the diode readings into patient dose. The diode was irradiated at various gantry angles （increments of 45~）, various Field Sizes and various Source to Surface Distances （SSDs）. Results The maximal response variation in the angular response with respect to an arbitrary angle of 0~ was 1.9%, and the minimum variation was 0.5%. The response of the diode with respect to various field siz- es showed the minimum and the maximum variations in the measured dose from the diode; the calculated doses were -1.6% （for 5 cm x 5 cm field size） and 6.6% （for 40 cm x 40 cm field size）. The diode exhibited a significant perturbation in the response, which decreased with increasing SSD. No discrepancies larger than 5% were detected between the expected dose and the measured dose. Conclusion The results indicate that the diodes exhibit excellent linearity, dose reproducibility and minimal anisotropy; that they can be used with confidence for patient dose verification. Furthermore, diodes render real time verification of the dose delivered to patients.

Dosimetric consequences of tumor volume changes after kilovoltage cone-beam computed tomography for non-operative lung cancer during adaptive intensity-modulated radiotherapy or fractionated stereotactic radiotherapy

Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.

Clinicopathological characteristics and treatment of carcinosarcoma of the female genital tract

Carcinosarcomas of the female genital tract are highly aggressive and rare tumors,differing from other malignant gynecological tumors in that they contain both malignant carcinomatous and sarcomatous elements. Because carcinosarcomas are rapidly progressive,less sensitive to chemotherapy or radiotherapy,and have a high probability of recurrence,patients with advanced uterine and ovarian carcinosarcomas have poorer survival than those with endometrial or high-grade serous carcinomas. Although the treatment strategies are controversial,a comprehensive management approach is recommended,which involves complete debulking surgery followed by adjuvant chemotherapy and/or radiotherapy. Molecular-targeted therapies are promising for the management and improvement in the overall survival of patients with carcinosarcomas.

Novel patterns of cancer genome evolution

Cells usually undergo a long journey of evolution during the progression from normal to precancerous cells and finally to full-fledged cancer cells. Multiple genomic aberrations are acquired during this journey that could either act as drivers to confer significant growth advantages or act as passengers with little effect on the tumor growth. Recent advances in sequencing technology have made it feasible to decipher the evolutionary course of a cancer cell on a genome-wide level by evaluating the relative number of mutated alleles. Novel terms such as chromothripsis and chromoplexy have been introduced to describe the newly identified patterns of cancer genome evolution. These new insights have greatly expanded our understanding of the initiation and progression of cancers,which should aid in improving the efficiency of cancer management and treatment.

Clinical and pathological observations of retroperitoneal paraganglioma in 32 cases

Objective The aim of the study was to investigate the clinical manifestations, pathologic features, dif- ferentiation, and diagnosis of retroperitoneal paraganglioma. Methods The clinical manifestations, histopathologic morphology, immunohistologic features, treatment, and prognosis were analyzed in 32 cases of retroperitoneal paraganglioma, and the literature was re- viewed. Results Low back pain was the main symptom of retroperitoneal paraganglioma, and patients often presented with increased blood pressure. Blood vessels were abundant in the neoplasm of retroperitoneal paraganglioma, and pathologic diagnosis showed that the cells of tumors were rich in cytoplasm, and some were basophilic. Immunohistochemical study showed that CgA, Syn, S-100, and Ki-67 （2%-30%） were expressed, while Melan-A and CK were not. The patients were treated with surgical resection. Thirteen cases were followed up, and no recurrence or metastases have been observed. Conclusion The diagnosis of retroperitoneal paraganglioma should be confirmed by morphologic features and immunophenotype. Patients should be followed-up due to the potential for malignancy.