Research On Prognostic Factors And Safety Of High Intensity Focused Ultrasound And Gemcitabine For The Treatment Of Advanced Pancreatic Cancer

IntroductionPancreatic cancer is a common abdominal malignant tumor, there is a trend that the incidence is increasing gradually in recent ten years. Pancreatic cancer is divided into pancreatic head carcinoma and body and tail carcinoma of pancreas. In pathology, The major fungus is catheter cell adenocarcinomas. In recent years, more and more researches argue that smoking is a major risk factor for pancreatic cancer. Surgical resection is the most effective treatment method, but the problem is that80%of the patients with pancreatic cancer have lost the operative option. Palliative treatment has became the major treatment of unresectable pancreatic cancer. Scholars in many countries have been exploring and practicing constantly in this aspect. Chemotherapy is the main treatment for advanced pancreatic cancer and gemcitabine has been approved by the FDA as firs-line agents for the treatment of pancreatic cancer. High intensity focused ultrasound is also a kind of physical palliative treatment, the effectiveness in the treatment of the medium-term and advanced pancreatic cancer has been generally recognized. Both of them can increase the survival time of patients and disease control rates. The life quality of patients is also can be improved. Domestic and international research shows that there is chemotherapy sensitization effect. Therefore, trying to combine the high intensity focused ultrasound with gemcitabine in the treatment of the medium-term and advanced unresectable pancreatic cancer in recent years has been researched in the multi-center clinical trial. But relevant clinical researches mainly focuses on the effectiveness assessment, there are much less systematical corresponding researches on prognostic factors of advanced pancreatic cancer. The security of high intensity focused ultrasound have also been studied, most of them stop proceeding at the clinic observation, especially in the field of abdominal ultrasound channel tissues and organs injury. Whether effectiveness or security still needs to be studied further.ObjectiveThe purpose of this study is to evaluate effectiveness, prognostic factors and application value of HIFU joint gemcitabine in the treatment of the medium-term and advanced pancreatic cancer,and to make further evaluation on safety of HIFU channel tissues and organs injury in vivo and in clinical research.Methods:1. Clinical analysis of prognostic factors and efficacy on High intensity focused ultrasound and gemcitabine for the treatment of advanced pancreatic cancerSince the the foundation of ultrasonic waves tumor center in July2009, already191advanced pancreatic cancer patients have accepted HIFU, and76of them also accepted chemotherapy after HIFU. Sixty-one patients met the inclusion criteria.5patients with liver metastasis received HIFU at the same time both in hepatic metastases and pancreatic tumors. All61patients were received chemotherapy(gemcitabine) in3days after HIFU. Pain relief, local tumor control rate and complications were observed after HIFU treatment. Survival was estimated from the date of initiation of treatment by Kaplan-Meier method.2. The histopathological observation of abdominal ultrasound channel and target area on the pancreatic cancer by High Intensity Focused UltrasoundA total of11advanced unresectbale patients were in spected in The second artillery force general hospital from Mar,2010to Nov,2011. According to the2002International Union Against Cancer (UICC),there were10patients with stage Ⅲ, and1patient of primary hilar cholangio-carcinoma (HCCA) with metastasis to head of pancreas. All patients were diagnosed as the medium-term and advanced unresectbale pancreatic cancer by our department and other famous hospital in Beijing. HIFU ablation therapy was done at first, and all patients would receive safety assessment of HIFU though CT and MRI findings in them and clinical presentation after HIFU. All the patients would undergo operation (whipple procedure) in7to10days after HIFU. The ultrasound channel tissues and organs(the skin、abdominal muscle tissue、gastrointestinal tract、the tumor and its adjacent organs) by adopting general and light microscopy. Evaluate the effects and safety of HIFU in the treatment of pancreatic cancer by combining with observing histopathological changes of surgical resection, including distal gastric tissue, distal bile duct, duodenum, jejunum, gall bladder, pancreas.Results:1. Clinical analysis of prognostic factors and efficacy on High intensity focused ultrasound and gemcitabine for the treatment of advanced pancreatic cancerThere were no severe complications or adverse events related to HIFU therapy in any of the patients treated. The median survival time was6.68months, six months and one year survival rates were50.8%and3.3%. In this study the cancer related pain was relieved in65.5%patients(40/61)after HIFU (complete remission (CR) in17cases, part remission (PR) in23cases); Recent effect assessment:complete remission (CR)0cases, part remission (PR)6patients (9.8%), stable (SD)34cases, progressive disease (PD)21cases (34.4%); KPS score and liver metastasis were identified as independent predictors for overall survival by Cox proportional regression analysis. HIFU-related postoperative common complications were skin mild thermal damage and the adverse reactions of chemotherapy did not increase significantly.2. The histopathological observation of abdominal ultrasound channel and target area on the pancreatic cancer by High Intensity Focused UltrasoundThe gross examination after HIFU indicates that there were7patients appeared mild skin damage and1patient appeared moderate skin damage. No severe cases appear in this study. The subcutaneous nodule also could be touched in7patients. The subcutaneous nodule and the changes of skin exterior are nonexistent immanent inevitable connection. The fibrosis of Ultrasound channel subcutaneous deep fascia and partial abdominal wall muscle could be observed and hemorrhagic change happened in1case. There were no obvious visible changes about the tissues and the organs could be seen during the operation. And no significant pathological changes of surgical resection (the skin、abdominal muscle tissue、gastrointestinal tract and adjacent tissues or organs) could be observed by light microscope.Conclusion:1. The mode of high intensity focused ultrasound combined with gemcitabine is effective in the treatment of advanced pancreatic cancer. This treatment model for advanced pancreatic cancer did not increase the adverse reactions of chemotherapy. Part of these patients with pancreatic cancer can obtain long-term survival through this treatment model.2. KPS score and patients with liver metastasis were identify as independent prognostic factors. There were no significant difference of age, sex, tumor size, the location of the tumor, TNM stage, the ratio and chemotherapy times for the survival period.3. It indicated that the mild skin damage is common complication after HIFU and subcutaneous nodule could also be inspected. The thermal injury of the subcutaneous adipose tissues, superficial temporal fascia and deep temporal fascia may play multiple roles,4. Coagulation necrosis could be found in the target region during operation and Light microscope also showed that coagulated necrosis occurred. The experimental results demonstrate the validity of HIFU.5. No obvious visible changes about the tissues and the organs could be seen during the operation and no significant pathological changes of surgical resection (the skin, abdominal muscle tissue、gastrointestinal tract and adjacent tissues or organs) could be observed by light microscope. The injury of HIFU to the Ultrasound Channel Tissues and Organs of Human is limited. The safety of HIFU in the treatment of pancreatic cancer is confirmed.