基于《金匮要略》正邪理论观中医对癌病防治特色

《金匮要略》作为我国颇具代表性的杂病治疗论著,其关于癌病防治相关理论观点自成体系且对后世中医影响深远,至今仍具有较高的研究与应用价值。从正邪理论角度来讲,正邪对疾病的发生以及发展具有决定作用,从中医正邪理论分析癌症预防与治疗可为癌症防治打开新思路。本文从《金匮要略》正邪理论角度对癌病中医防治特色进行论述,重点从病机、预防以及治疗这几个角度展开探讨,期望能为中医癌症防治工作提供些许助益。

Hepatocellular carcinoma: Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Mechanisms of action of leptin in preventing gastric ulcer

To investigate the effects of leptin （1-20μg/kg） on acidified ethanol （AE）- and indomethacin （Indo）-induced gastric lesions in rats and compare it with ranitidine, lansoprazole, and omeprazole and to determine its mechanisms of actions.METHODS： Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors （PPIs） lansoprazole and omeprazole, or H2-receptor antagonist ranitidine 30 min before AE or Indo was evaluated.A radioimmunoassay was used to determine the PGE2 concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content.RESULTS： Subcutaneous administration of leptin, two PPI slansoprazole and omeprazole or H2-receptor antagonist ranitidine 30 min before AE or Indo produced a dosedependent and reproducible inhibition of gastric ulcers （GUs）. This inhibition was found to be more potent than other antagonists used. In N^G-nitro L-arginine methyl ester （L-NAME）-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced,compared to rats without L-NAME pretreatment. However,the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE2 level in the gastric glandular tissues. Leptin also increased mucus secretion.CONCLUSION： The results of the present study show that leptin inhibits GU formation by AE or Indo in a dosedependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.

Prognostic factors of young patients with colon cancer after surgery

AIM： To investigate the prognostic factors of 96 young patients with colon cancer within a cancer center by univariate and multivariate analysis. METHODS： A total of 723 patients with colon cancer were treated surgically during a period of 10 years. Ninty six of them were 40 years old or younger. R0, R1 and R2 operations were performed in 69 （71.9%）, 4 （4.1%） and 23 patients （24%）, respectively. Left hemicolectomy was performed in 43 patients, right hemicolectomy in 37 patients, transverse colon resection in 9 patients and low anterior resection in 7 patients. Cox multivariate regression analysis was performed to identify predictors of survival. RESULTS： The operation mortality was 0%, 54 patients died within 111 mo after operation due to occurrence or metastases of the tumor. Liver, lung and bone metastases occurred in 3, 1 and 5 patients, respectively. The mean survival time for all patients was 77.9 ± 5.01 mo and the overall 3-, 5- and 10- year survival rates were 66.68%, 58.14% and 46.54%, respectively. In the univariate survival analysis, patient age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastases, liver metastases and TNM stage were found to be predictors of survival in young patients with colon cancer. In the Cox-regression analysis, blood transfusion and lymphatic invasion were determined as independent prognostic factors of survival. CONCLUSIONS： Age, type of operation, radical resection, blood transfusion, histological type, diameter of tumor, depth of tumor invasion, lymphatic invasion, distant metastasis and TNM stage are the predictors of survival in young patients with colon cancer after surgery.

Prognostic value of lateral lymph node metastasis for advanced low rectal cancer

AIM： To evaluate the risk factors for lateral lymph node metastasis in patients with advanced low rectal cancer, in order to make the effective selection of patients who could benefit from lateral lymph node dissection, as well as the relationship of lateral lymph node metastasis with local recurrence and survival of patients with advanced low rectal cancer. METHODS： A total of 96 consecutive patients who underwent curative surgery with lateral pelvic lymphadenectomy for advanced lower rectal cancer were retrospectively analyzed. The relation of lateral lymph node metastasis with clinicopathologic characteristics, local recurrence and survival of patients was identified. RESULTS： Lateral lymph node metastasis was observed in 14.6% （14/96） of patients with advanced low rectal cancer. Lateral lymph node metastasis was detected in 10 （25.0%） of 40 patients with tumor diameter ≥ 5 cm and in 4 （7.1%） of 56 patients with tumor diameter 〈 5 cm. The difference between the significant （X^2 = 5.973, P = two groups was statistically 0.015）. Lateral lymph node metastasis was more frequent in patients with 4/4 diameter of tumor infiltration （7 of 10 cases, 70.0%）, compared with patients with 3/4, 2/4 and 1/4 diameter of tumor infiltration （3 of 25 cases, 12.0%; 3 of 45 cases, 6.7%; 1 of 16 cases, 6.3%） （X^2 = 27.944, P = 0.0001）. The lateral lymph node metastasis rate was 30.0% （9 of 30 cases）, 9.1% （4 of 44 cases） and 4.5% （1 of 22cases） for poorly, moderately and well-differentiated carcinoma, respectively. The difference between the three groups was statistically significant （X^2 = 8.569, P = 0.014）. Local recurrence was 18.8% （18 of 96 cases）, 64.3% （9 of 14 cases）, and 11.0% （9 of 82 cases） in patients with advanced low rectal cancer, in those with and without lateral lymph node metastasis, respectively. The difference between the two groups was statistically significant （X^2 = 22.308, P = 0.0001）. Kaplan-Meier survival analysis showed significant improvements in median survival （80.9 ± 2.1 m, 95% CI： 76.7-85.1 m vs 38 ± 6.7 m, 95% CI： 24.8-51.2 m） of patients without lateral lymph node metastasis compared with those with lateral lymph node metastasis （log-rank, P = 0.0001）. CONCLUSION： Tumor diameter, infiltration and differentiation are significant risk factors for lateral lymph node metastasis. Lateral pelvic lymphadenectomy should be performed following surgery for patients with tumor diameter ≥ 5 cm. Lateral lymph node metastasis is an important predictor for local recurrence and survival in patients with advanced low rectal cancer.

Prognosis following transcatheter arterial embolization for 121 patients with unresectable hepatocellular carcinoma with or without a history of treatment

AIM： To retrospectively evaluate the prognosis of patients with hepatocellular carcinoma （HCC） with or without a history of therapy for HCC following transcatheter arterial embolization （TAE）. METHODS： One hundred and twenty-one patients with HCC treated with TAE from 1992 to 2004 in our hospital were enrolled in this study. Eighty-four patients had a history of treatment for HCC, while 37 did not. At the time of entry, patients with extra-hepatic metastasis, portal vein tumor thrombosis, or Child-Pugh class C were excluded. TAE was repeated when recurrence of HCC was diagnosed by elevated tumor markers, or ultrasonography or dynamic computed tomography findings. RESULTS： Tumor size was larger and the number of tumors was fewer in patients without past treatment （P〈0.01）. However, there were no differences in tumor node metastasis （TNM） stage or survival rate between the 2 groups. A bilobular tumor and high level of α-fetoprotein （AFP） （〉100 ng/mL） were factors related to a poor prognosis in patients with a history of HCC. CONCLUSION： The prognosis following TAE is similar between HCC patients with and without past treatment. Early diagnosis of HCC or recurrent HCC and obtaining good local control against HCC before entry to a repeated TAE course can improve prognosis.

Prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and micronucleus assay

AIM： To investigate the prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and rnicronucleus assay. METHODS： Clonogenic assay, flow cytometry, and CB micronuclei assay were used to survey the cell survival rate, radiation-induced apoptosis and rnicronucleus frequency of hepatocarcinorna cell lines SMMC-7721, HL-7702, and HepG2 after being irradiated by X-ray at the dosage ranging 0-8 Gy. RESULTS： After irradiation, there was a dose-effect relationship between rnicronucleus frequency and radiation dosage among the three cell lines （P〈0.05）. A positive relationship was observed between apoptosis and radiation dosage among the three cell lines. The HepG2 cells had a significant correlation （P〈0.05） but apoptosis incidence had a negative relationship with rnicronucleus frequency. There was a positive relationship between apoptosis and radiation dosage and the correlation between 5MMC-7721 and HL-7702 cell lines had a significant difference （P〈0.01）. After irradiation, a negative relationship between cell survival rate and radiation dosages was found among the three cell lines （P〈0.01）. There was a positive relationship between cell survival rate and rnicronucleus frequency （P〈0.01）. No correlation was observed between apoptosis and cell survival rate. CONCLUSION： The radiosensiUvity of hepatocarcinoma cells can be reflected by apoptosis and rnicronuclei. Detection of apoptosis and rnicronuclei could enhance the accuracy for predicting radiosensitivity.

Hepatocellular carcinoma prevention:A worldwide emergence between the opulence of developed countries and the economic constraints of developing nations

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm, the major cause of death in patients with liver cirrhosis, and the third most common cause of cancer-related death in the world. The geographic distribution of HCC varies significantly and 80% of cases occur in developing countries (Far East and South Asia) where the prevalence of viral hepatitis is higher. The treatment of HCC is difficult because most patients are diagnosed when the tumour is in an advanced stage and is not amenable to potential curative therapy, thus prevention is the key to reducing HCC and its related morbidity and mortality. HCC is unique among cancers, occurring mostly in patients with a known risk factor. Ninety percent of HCCs develop in the context of chronic liver diseases and mainly in patients with cirrhosis. Viral hepatitis is the most common cause of HCC worldwide, followed by alcoholic liver disease (ALD) and other causes such as non-alcoholic fatty liver disease (NAFLD), genetic haemocromatosis (GH) and primary biliary cirrhosis in an advanced stage (Ⅲ- Ⅴ). In certain areas of the People’s Republic of China, exposure to aflatoxin and HBV infection are thought to be responsible for the extraordinary high risk of HCC. Substantial progresses in the prevention of virusl-related hepatitis (screening of blood units, use of disposable sanitary tools, HBV vaccination) have been achieved in developed countries, but in the same areas, alcohol- and dysmetabolism-related HCCs are emerging problems which require specific interventions in terms of public health measures. In developing countries, economic constraints limit the development of any program for the prevention of viral hepatitis transmission (including health education campaigns, healthcare politics, primary prevention and the improvement of hygienic and sanitary conditions). When viral liver disease is established, only a minority of patients are treated worldwide and benefit a possible preventive effect of medical treatment onHCC development. Thus the real contribution of medical treatment to HCC prevention in patients with chronic viral hepatitis is small. Great efforts are needed to identify more effective medical measures for primary and secondary prevention of HCC.

Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

To study the inhibitory effect of Huqi San （Qi- protecting powder） on rat prehepatocarcinoma induced by diethylinitrosamine （DEN） by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes. METHODS： A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene （AAF） to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. T-glutamy-transpeptidase-isoenzyme （T-GTase） was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine （OHdG） formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods. RESULTS： The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before （1 wk） and after DEN exposure （4 wk）. Huqi San- treated rats showed a significant decrease in number of T-GT positive foci （P 〈 0.001, prevention group： 4.96-0.72 vs 29.46-2.17; large dose therapeutic group： 7.53-0.88 vs 29.46-2.17）. On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats. CONCLUSION： Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesions induced by DEN.

Prognostic factors in patients with stage IV non-small cell lung cancer

Objective： To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer （NSCLC） with distant metastasis and establish a reliable model of clinical prognostic index. Methods： From January 1990 to April 2005, 313 primary NSCLC patients with metastasis, who had been treated in Shanghai Chest Hospital, were reviewed. Survival time was estimated according to the Kaplan-Meier method. Cox proportional hazard regression model was used for multivariate analysis. Results：Among the 313 cases of non-small cell lung cancer （NSCLC） at stage Ⅳ, there were 218 and 95 patients with metastasis to single and different organs, respectively. The overall median survival time for all 313 cases of NSCLC patients was 10.8 （9.00, 12.30） months and the overall 1-, 2-, 3-, 4- and 5-year survival rate was 45%, 18%, 12%, 4% and 0%. There were 63, 174, 127, 36, 18, 11 and 5 patients with metastasis to brain （20.13%）, bone （55.59%）, lung （40.58%）, liver （11.50%）, adrenal gland （5.75%）, subcutaneous （3.51%） and others, respectively. The survival time was shortest in subcutaneous metastasis （4.6 months）, and liver 7.0 months, brain 8.0 months, adrenal gland 8.6 months, bone 10.6 months, lung 11.8 months. Kaplan-Meier estimation showed that patients anatomic typing, KPS, numbers of organ with metastasis, appetite, liver, adrenal gland and subcutaneous metastasis, body weight loss, smoking, index of smoking, chemotherapy, cycles of chemotherapy were the predictors of survival. Multivariate analysis showed survival statistically significant correlation with anatomic typing, KPS, appetite, liver and subcutaneous metastasis, body weight loss, cycles of chemotherapy. The relative risk （RR） was 1.51, 1.97, 1.55, 1.67, 2.56, and 2.56 respectively. Conclusion： Survival time decreases distinctly in patients who had distant metastasis to more than two different organs （P〈0.01）. Bone is the commonest organ for distant metastasis in lung cancer. The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis. Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis, anatomic typing, KPS, appetite, body weight loss, cycles of chemotherapy.

Adenocarcinoma of gastric cardia in the elderly: Surgical problems and prognostic factors

AIM： To analyze retrospectively, our results about patients who underwent surgical treatment for adenocarcinoma of the cardia in relation to age, in order to evaluate surgical problems and prognostic factors. METHODS： From January 1987 to March 2003, 140 patients with adenocarcinoma of the cardia underwent resection in the authors＇ institution. They were divided into three groups with regard to age. Patients 〈70 and 〉 60 year old （31） were excluded; we also excluded 18 out of 109 patients with poor general status or systemic metastases. So, we compared 51 elderly （≥ 70 year old） and 58 younger patients （≤ 60 year old）. The treatment was esophagectomy for type I tumors, and extended gastrectomy and distal esophagectomy for type Ⅱ and Ⅲ lesions. RESULTS： Laparotomy was carried out in 91 patients （83.4%）, 38 in the elderly （74.5%） and 53 in younger patients （91.3%, P〈0.05）. Primary resection was performed in 81 cases （89%） without significant differences between the two groups. Postoperative death was higher in the elderly （12.1%） than the other group （4.1%, P〈0.05）, while morbidity was similar in both groups. A curative resection （R0） was performed in 59 patients （72.8%）, 69.6% in the elderly and 75% in the younger group （P〉0.05）. The overall 3- and 5-year survival rates were 26.7% and 17.8% respectively for the elderly and 40.7% and 35.1% respectively for younger patients （P = 0.1544）. Survival rates were significantly associated with R0 resection, pathological node-poskive category and tumor differentiation in both groups.CONCLUSION： As the age of the general population increases, more elderly patients with gastric cardia cancer will be candidates for surgical resection. Age alone should not preclude surgical treatment in elderly patients with gastric cardia cancer and a tumor resection can be carried out safely. Certainly, we should take care in defining the surgical treatment in elderly patients, particularly as regarding the surgical approach; although the surgical approach does not influence the survival rate, the transhiatal way still remains the best one due, to the lower incidence of respiratory morbidity and thoracic pain.

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 published 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 T2- T4, 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.

The Use of Postoperative Serum HS-AFP and GGTⅡfor Judgment of the Prognosis for Hepatocellular Carcinoma patients

OBJECTIVE To investigate the clinical value of hepatoma-specific alpha-fetoprotein （HS-AFP） and gamma-glutamyltransferase Ⅱ （GGT Ⅱ） for judgment of postoperative prognosis of patients with hepatocellular carcinoma （HCC）. METHODS HS-AFP was separated and determined using native polyacrylamide electrophoresis with a discontinuous buffer system and Western blots. GGT Ⅱ was separated with native polyacrylamide electrophoresis with a discontinuous buffer system and detected by enzyme staining. Forty cases with HCC underwent serial determination of HS-AFP and GGT Ⅱ before and after radical excision. The correlations were analyzed between the two indices and survival time. RESULTS In the 40 cases with HCC, before radical excision the positive rates of HS-AFP and GGT II were 57.5% and 67.5% respectively, with the positive rate of combined HS-AFP and GGT Ⅱ reaching 80.0%. After operation, the recurrence and metastasis rate in the groups with positive HS-AFP and GGT Ⅱ were 90.9% and 58.8% respectively, while in the groups with negative HS-AFP and GGT Ⅱ the rates were 20.7% and 26.1% respectively. Recurrence and metastasis occurred in all cases with both postoperative positive HS-AFP and GGT Ⅱ but only in 9.5% of the cases in whom both postoperative HS-AFP and GGT Ⅱ were negative. Univariate analysis revealed that postoperative HS-AFP and GGT Ⅱ were related to the prognosis in HCC. CONCLUSION Postoperative serum HS-AFP and GGT Ⅱ are very useful in predicting the prognosis of HCC patients.

Expression of E-Cadherin in Oral Squamous Cell Carcinoma is Associated with Clinical Prognosis

OBJECTIVE To investigate the correlation of E-cadherin expression with clinicopathological parameters and prognosis of patients with oral squa- mous cell carcinoma. METHODS We examined the expression of the protein E-cadherin in 43 oral squamous cell carcinoma (SCC) surgical speciments by SABC im- munohistochemistry. RESULTS There was a significant correlation between the level of E- cadherin expression and tumor stage (P=0.024), invasive pattern (P= 0.009) and lymph node metastasis (P=0.023). No relation was found with age (P=0.084), sex (P= 1.356) and differentiation (P=0.877). Using the Kaplan-Meier method we demonstrated that those cases which showed E-cadherin expression (-) or (+) had a significantly poorer prognosis compared those cases which showed expression (++) or (+++) (P= 0.0146). CONCLUSION E -cadherin, is an important indicator of clinical diag- noses and prognositic marker for oral SCC patients.