Pancreatic cancer–Adjuvant therapy

Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.     

胰腺癌:辅助治疗

Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%-15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation （with or without maintenance chemotherapy） has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence （from the ESPAC-1 trial） is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.     

The relationship between the pathological changes and response rate (RR) in non-small cell lung cancer treated by neoadjuvant chemotherapy with mitomycin (MMC), vindesine (VDS) and cisplatin (DDP) combination

Lung cancer is the leading cause of male cancer death in the big cities in China. The mortality is growing recent years. It has been confirmed that the best treatment for non-small cell lung cancer is the surgery-based multimodality therapy. But only 20% of NSCLC patients present with stage I and II disease and can be resected completely when the diagnosis is established. It is a trend for stage II and IIIa patients to use adjuvant chemotherapy in order to improve the 5-year survival rat…     

胰腺癌:姑息性支架术治疗

Pancreatic cancer remains a common and very lethal malignancy with a median survival of approximately 6 months. Surgical resection offers the only potentially curative approach but many patients （80% or more） are ineligible for this kind of therapy, because of age, comorbidities, or locally advanced or metastatic disease that does not benefit from resection. Thus, for many patients with pancreatic cancer treatment remains palliative and endoscopic therapy to relieve bile duct or gastric outlet obstruction becomes of special importance. Although both surgical and non surgical palliative procedures can relieve biliary and duodenal obstruction particularly endoscopic treatment with plastic prostheses or self expanding metal stents was shown to be not only highly effective but also to be burdened with only few complications. The present article summarizes the palliative endoscopic treatment in patients with non resectable pancreatic cancer.     

Pancreatic cancer–Palliative therapy: stenting

Pancreatic cancer remains a common and very lethal malignancy with a median survival of approximately 6 months. Surgical resection offers the only potentially curative approach but many patients (80% or more) are ineligible for this kind of therapy, because of age, comorbidities, or locally advanced or metastatic disease that does not benefit from resection. Thus, for many patients with pancreatic cancer treatment remains palliative and endoscopic therapy to relieve bile duct or gastric outlet obstruction becomes of special importance. Although both surgical and non surgical palliative procedures can relieve biliary and duodenal obstruction particularly endoscopic treatment with plastic prostheses or self expanding metal stents was shown to be not only highly effective but also to be burdened with only few complications. The present article summarizes the palliative endoscopic treatment in patients with non resectable pancreatic cancer.     

NEOADJUVANT CHEMOTHERAPY AND OPERATION FOR INVASIVE MASAOKE STAGE Ⅲ AND Ⅳa THYMOMA

Operation combined with postoperativeradiotherapy have been used as primary treatments for patients with invasive thymoma, but the involvement of thoracic large vessels or other important viscera (Masaoke stage Ⅲ) and dissemination of pericardium or pleural(Masaoke stage Ⅳa) are difficult for radical resection and proved poor in prognosis. Although the use of neoadjuvant chemotherapy to invasive thymoma has been reported abroad since 1980s, only case report has been reported in China. From …     

Chemotherapy for cholangiocarcinoma:An update

Cholangiocarcinomas(bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic,perihilar and extrahepatic bile ducts.Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management.First of all,it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients.Overall,cholangiocarcinomas have a very poor prognosis.The 5 year survival rate is 5%-10%.In cases with a potentially curative surgery,5 year survival rates of 25%-30% are reported.Therefore,it is necessary to increase the cure rate from surgery,exploring the survival benefit of any adjuvant strategy.It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas.There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined.The most relevant studies in the adjuvant setting are one from Japan,the well known ESPAC-3 and BILCAP from the United Kingdom and a meta-analysis.We show the results of these trials.According to medical oncology guidelines,postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins,as well as for those with a complete resection but node-positive disease.Clinical trials are ongoing.The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients:(1) patients who have had surgery but with macroscopic residual disease;(2) patients with locally recurrent disease after potentially curative treatment;and(3) patients with locally unresectable disease at presentation.In these patients,surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local tumor effects.Nowadays,no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma.There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma.In systemic therapy,no single drug or combination has consistently increased median survival beyond the expected 8-12 mo.It is always recommended that patients enrol in clinical trials.Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin(or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone.Leucovorinmodulated 5-fluorouracil,capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status.After progression in patients with an adequate performance status,active regimens that could be considered include gemcitabine plus capecitabine,or erlotinib plus bevacizumab,for second line treatment.     

Complexity of molecular alterations impacts pancreatic cancer prognosis

Individualized cancer treatment(e.g.targeted therapy) based on molecular alterations has emerged as an important strategy to improve the current standardof-care chemotherapy.A large number of studies have demonstrated the importance of biomarkers not only in predicting prognosis but more importantly in predicting the response towards therapies.For example,amplification or mutation status of the two biomarkers HER2(human epidermal growth factor 2) and BRCA(breast cancer) can be used to decide on a specific targeted therapy in breast cancer.However,no biomarkers with a similar clinical impact have been identified in pancreatic ductal adenocarcinoma.Although many genome-wide and proteome-based high-throughput studies have identified candidate genes or proteins as promising biomarkers,none of them were eventually transferred into the clinical setting.Notably,the most reliable markers for predicting prognosis are still the tumor stage and grade and biomarkers for therapy response remain undefined.One reason lies in the lack of systemic approaches to analyze the complexity of dominating cancer pathways and the impact of such signal complexity on prognosis and therapy response.     

Rational Operation for Primary Gastric Carcinoma with Liver Metastasis

OBJECTIVE To investigate the prognosis of advanced gastric carcinoma patients with liver metastasis, and provide a foundation for rational operations. METHODS The operations and prognosis of 102 primary gastric carcinoma patients with liver metastasis were studied retrospectively. RESULTS In gastric carcinoma patients with H1 metastasis who underwent a resection operation, the 6-month, 1- and 2-year post-operative survival rates were 61%, 42% and 7%. There was a statistically significant difference in survival between resected and non-resected patients （P=0.000） in gastric carcinoma cases with H2 metastasis, resection operations resulted in 54%, 16% and 8% respective survival rates, with no significant difference compared to patients not receiving a resection （P=0.132）. Gastric carcinoma patients with H3 metastasis who received a resection operation showed 25%, 13% and 0% respective survivals with no significantly better prognosis compared to the non-resected cases （P=0.135）. There was no statistically significant difference in survival between the cases with or without peritoneal metastasis （P=0.152）. CONCLUSION A resection operation provides a better prognosis for gastric carcinoma patients with H1 metastasis independent of peritoneal metastasis, but resection has no benefit for gastric carcinoma cases with H2 or H3 metastasis. Peritoneal metastases are not the significant influencing factor for the prognosis of gastric cancer with liver metastasis.     

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective:No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC).This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive,completely resected thoracic ESCC patients.Methods:We conducted a prospective phase Ⅱ trial.Patents had pathologically node-positive thoracic ESCC with negative margins.Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort.The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d.Results:Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy.The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time.Of the 43 patients with adjuvant chemotherapy,37 (86.0％) patients completed 4 to 6 cycles of chemotherapy.The 3-year DFS rates were 56.3％ in the adjuvant group and 34.6％ in the control group (P=0.006).The 3-year OS rates were 55.0％ in the adjuvant group and 37.5％ in the control group (P=0.013).Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).Conclusions:Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive,curatively resected thoracic ESCC patients.These conclusions warrant further study in randomized phase Ⅲ clinical trials.     

Clinical importance and surgical decision-making regarding proximal resection margin for gastric cancer

Because of the intramural spread of gastric cancer,a sufficient length of a resection margin has to be attained to ensure complete excision of the tumor.There has been debate on an adequate length of proximal resection margin(PRM) and its related issues.Thus,the objective of this article is to review several studies on PRM and to summarize the current evidence on the subject.Although there is some discrepancy in the recommended values for PRM between authors,a PRM of more than 2-3 cm for early gastric cancer and 5-6 cm for advanced gastric cancer is thought to be acceptable.Once the margin is confirmed to be clear,however,the length of PRM measured in postoperative pathologic examination does not affect the patient’s survival,even when it is shorter than the recommended values.Hence,the recommendations for PRM length should be applied only to intraoperative decision-making to prevent positive margins on the final pathology.Given that a negative resection margin is the ultimate goal of determining an adequate PRM,development and improvement of reliable methods to confirm a negative resection margin intraoperatively would minimize the extent of surgery and offer a better quality of life to more patients.In the same context,special attention has to be paid to patients who have advanced stage or diffuse-type gastric cancer,because they are more likely to have a positive margin.Therefore,a wider excision with intraoperative frozen section(IFS) examination of the resection margin is necessary.Despite all the attempts to avoid positive margins,there is still a certain rate of positive-margin cases.Since the negative impact of a positive margin on prognosis is mostly obvious in low N stage patients,aggressive further management,such as extensive re-operation,is required for these patients.In conclusion,every possible preoperative and intraoperative evaluation should be thoroughly carried out to identify in advance the patients with a high risk of having positive margins;these patients need careful management with a wider excision or an IFS examination to confirm a negative margin during surgery.     

Operable Breast Cancer： a Clinical Analysis of 6,263 Cases

OBJECTIVE In Europe and America breast cancer commonly occurs in women of middle and old age, with a median age of about 57 years. Modified radical mastectomy now called standard radical mastectomy, has taken the place of traditional radical mastectomy. Patients with breast cancer at an early stage commonly receive BCT (breast conservative therapy). The TNM stage (especially the lymph node status) affects the prognosis, and adjuvant therapy can improve survival. In China, only a few reports have been pubIished studying large numbers of breast cancer patients. This study was designed to analyze the clinical features, surgical pattern and treatment outcome of resectable breast cancer, as well as to explore the prognostic factors and the effect of adjuvant therapy, with a goal to improve the level of diagnosis and treatment.METHODS Records of the 6,263 patients with resectable breast cancer who had been admitted into our hospital from June 1964 to June 2003 were analyzed retrospectively.RESULTS Of the 6,263 cases, 98.8% were female. Breast cancer occurred most frequently in patients of ages 40～49 years (41.0%), especially in patients 45～49 years old (25.2%). A breast lump, which occurred in 96.2% of the patients, was the main clinical manifestation. The overall 5- and 10-year survival rates were 75.16% and 40.44%. Of the patients in TNM stages 0-1,Ⅱ, and Ⅲ, the 5-year survival rates were 96.8%, 73.7% and 46.4% respectively and the 10-year survival rates were 78.7%, 64.6% and 33.5% respectively. The 5-, and 10-year survival rates were higher in the lymph node negative group than in the lymph node positive group (80.3% vs. 55.6%, and 59.2% vs. 31.9%, P＜0.01). Since the 1980s there was no significant difference in survival rates of patients who received a radical mastectomy compared to a modified radical mastectomy(P＞0.05). Of the 73 patients who underwent breast conservative therapy, no local recurrence or metastasis occurred during a maximal follow-up of 17 years. Of the patients in stage T2T4, the 5-, and 10-year survival rates were significantly higher in the group treated with adjuvant chemotherapy compared to the non-chemotherapy group (78.2% vs. 60.1%, and 48.9% vs. 30.7%, P＜0.01).CONCLUSION According to our data, breast cancer most frequently occurred in patients of ages 45～49 years. The TNM stage (especially the lymph node status) relates to breast cancer prognosis. The prognosis was worse in patients with positive lymph nodes compared to the patients with negative lymph nodes. The efficacy of a modified radical mastectomy is equal to that of a radical mastectomy, and breast conservative therapy can be applied to patients in an early stage. Adjuvant chemotherapy and endocrine therapy can improve the survival of resectable breast cancer patients.     

术前支气管动脉灌注化疗在肺癌手术中的临床研究

Objective： How to improve the postoperative 5-year survival rate for lung cancer and to give more patients a chance of surgery have become research hotspots. The aim of this research is to evaluate the clinical and pathohistological responses and effects of preoperative bronchial artery infusion （BAI） chemotherapy in patients with locally advanced （stage Ⅲ） non-small cell lung cancer （NSCLC）. Methods： A total of 92 patients with locally advanced NSCLC were randomly divided into two groups. BAI group received BAI chemotherapy for 2 cycles before surgical resection. Surgery group received operation only. The complete resection rate and clinical response were compared between the two groups. Results： In the BAI group, the clinical response rate and the pathohistological response rate were 68.3% and 51.3%, respectively. The complete resection rate in the BAI group was 89.7%, which was significantly higher than that in the surgery group （72.5%） （P 〈 0.05）. The 1- and 2-year survival rate was 100.0% and 80.6% in the BAI group, and 94.1% and 60.0% in the surgery group. Conclusion： BAI neoadjuvant chemotherapy is safe and effective, which has a good clinical and pathohistological response. It might increase the complete resection rate of the tumor and improve the long term survival rate of stage Ⅲ NSCLC patients.     

A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage III-N2 Non Small Cell Lung Cancer

Objective: To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage III-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m2, D1, D5)/paclitaxel (175 mg/m2, D1) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy. Twenty-five percent of the patients had grade 3?4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P<0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage II-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.     

Investigation of the Effect of Neoadjuvant Chemotherapy on Stage Ⅱ Breast Cancer

OBJECTIVE To investigate the effect of neoadjuvant chemotherapy in treatment of Stage Ⅱ breast cancer. METHODS The data from 113 patients with breast cancer of the same pathologic type in Stage Ⅱ,during the period of 1995 to 2001,were analyzed retrospectively.Among the patients,47 were treated with neoadjuvant chemotherapy,and 66 received no adjuvant therapy before surgery（control group）.After the patients of the neoadjuvant chemotherapy group had received 2 courses of chemotherapy with the CMF regimen,the surgical procedure was conducted. RESULTS Complete remission（CR）was attained in 9 of the 47 cases receiving neoadjuvant chemotherapy and partial remission（PR）was reached for 22 cases.The rate of breast-conserving surgery was enhanced from 22.73%to 46.81%（P〈0.05）in the neoadjuvant treatment group. There was no difference in the 5-year overall survival（OS）and disease-free survival（DFS）rate between the two groups（P〉0.05）,but the 5-year OS and DFS of the cases with clinical tumor remission was higher compared to the control group（P〈0.05）. CONCLUSION Neoadjuvant chemotherapy can enhance the rate of breast conservation for Stage Ⅱ breast cancer and may improve the prognosis of the cases with clinical remission.     

Primary malignant melanoma of uterine cervix： a suggestion of new scheme of treatment combination

Historically, the lack of melanocytes in the vaginal and cervical mucus membranes has deterred the findings of primary melanomas. Mainly due to its rarity, difficulty to diagnose, and poor prognosis, there has been no absolute agreement on comprehensive treatment so far. In this case report, we present a case of a 46-year-old woman with primary malignant melanoma of uterine cervix. She underwent neo-adjuvant chemotherapy initially followed by a radical hysterectomy. After adjuvant concurrent chemo-radiation, the patient has been followed up for 24 months. So far, she has not shown any symptoms or signs of recurrence. Further studies with more cases based on variable combinations of treatment regimen have been on the way.     

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer（NSCLC） patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.     

The correlation between increased apoptosis and decreased peripheral blood WBC in patients receiving chemotherapy for ovarian cancer

As it is known, chemotherapy is an important adjuvant therapy for patients with ovarian cancer after operation, for ovarian cancers are still difficult to be discovered and diagnosed at early stage. Furthermore, ovarian cancer cells are sensitivity to the platinum-based chemotherapy regimens, a positive effect can also be achieved even for the patients at late stage and the survival duration of the patients can be prolonged, therefore, chemotherapy has become a crucial treatment for patients wi…     

Outcome of surgical resection in Klatskin tumors

Cholangiocarcinomas are the second most frequent primary hepatic malignancy,and make up from 5% to 30% of malignant hepatic tumours.Hilar cholangiocarcinoma(HCC) is the most common type,and accounts for approximately 60% to 67% of all cholangiocarcinoma cases.There is not a staging system that permits us to compare all series and extract some conclusions to increase the long-survival rate in this dismal disease.Neither the extension of resection,according to the sort of HCC,is a closed topic.Some authors defend limited resection(mesohepatectomy with S1,S1 plus S4b-S5,local excision for papillary tumours,etc.) while others insist in the compulsoriness of an extended hepatic resection with portal vein bifurcation removed to reach cure.As there is not an ideal adjuvant therapy,R1 resection can be justified to prolong the survival rate.Morbidity and mortality rates changed along the last decade,but variability is the rule,with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%,respectively.Conclusion:Surgical resection continues to be the main treatment of HCC.Negative resection margins achieved with major hepatic resections are associated with improved outcome.Preresectional management with biliary drainage,portal vein embolization and staging laparoscopy should be considered in selected patients.Additional evidence is needed to fully define the role of orthotopic liver transplant.Portal and lymph node involvement worsen the prognosis and long-term survival,and surgery is the only option that can lengthen it.Improvements in adjuvant therapy are essential for improving long-term outcome.Furthermore,the lack of effective chemotherapy drugs and radiotherapy approaches leads us to can consider R1 resection as an option,because operated patients have a longer survival rate than those who not undergo surgery.     

REVERSAL EFFECTS OF MIFEPRISTONE ON MULTIDRUG RESISTANCE(MDR) IN DRUG-RESISTANT BREAST CANCER CELL LINE MCF7/ADR IN VITRO AND IN VIVO

Breast cancer is one of the most common malignant tumors among women. Surgery is effective in the majority of cases but adjuvant or neoadjuvant chemotherapy plays an important role in the management of the patients with advanced and relapsed breast cancer[1]. However, cross-resistance to structurally and functionally unrelated anticancer agents, termed multidrug resistance(MDR), is a major obstacle to successful chemotherapy for breast cancer [2-3]. Although tens of reversal drugs have been f…