EPIDEMIOLOGICAL FEATURES FOR LUNG CANCER IN BEIJING

The epidemioiogical features of lung cancer in Beijing during 1977 ?1986 were analysed. The data collected showed that lung cancer ncidence and mortality rates ranks first among all other malignant tumor and had been on the increase from year to year. The mortality rate in urban area was higher than that in its suburbs. While the male incidence was higher than that of the female. The sex ratio of the male to female incidence rates was 1.56. The incidence rate rises with age. The lung cancer is one of the lesser prevised cancer and the five-year relative survival rate is 6.5% for both sexes in 19S2 ?1983. The lung cancer mortality rate in Beijing urban area is compared in this report with other countries in the world, and it is found that the female mortality rate of lung cancer in Beijing is among the highest.

MUTAGENICITY AND CARCINOGENICITY OF FISH SAUCE FROM A COUNTY WITH THE HIGH RISK FOR GASTRIC CANCER IN CHINA

The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.

Laparoscopy-assisted transanal total mesorectal excision for lower rectal cancer:A feasible and innovative technique

BACKGROUND Transanal total mesorectal excision(taTME)is a new technique with many potential technical advantages.Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery taTME.Laparoscopy-assisted taTME is a combination of techniques such as minimally invasive surgery,intersphincter-assisted resection,natural orifice extraction,ta minimally invasive surgery,and ultralow-level preservation of the anus.AIM To verify the feasibility and safety of an innovative technique of taTME for treatment of cancer located in the lower rectum.METHODS From January 2016 to March 2018,we attempted to perform laparoscopy-assisted taTME surgery in 24 patients with lower rectal cancer.RESULTS The new technique of laparoscopy-assisted taTME was successfully performed in all 24 patients.Mean operating time was 310.0 min and mean intraoperative blood loss was 69.1 mL.The mean time to passing of first flatus was 3.1 d,and mean postoperative hospital stay was 9.2 d.Two patients were given postoperative analgesics due to anal pain.Twenty-three patients were able to walk in first 2 d,and five patients had postoperative complications.CONCLUSION Laparoscopy-assisted taTME is suitable for selected patients with lower rectal cancer,and this technique is worthy of further recommendation.

Palliative Endoscopic Therapy for Cancer Patients with Esophageal Fistula

Objective： To find an effective treatment for advanced cancer patients with esophageal fistula. Methods： From 1998 to 2006, we studied 42 patients with advanced esophageal cancer and 5 lung cancer patients with carcinomatous esophageal fistula （3 females, 44 males, aged 29-92 years）. Ten patients with both esophageal cancer stricture and fistula were first dilated under endoscope, then a memory stent with a membrane was placed in the esophageal lumen. Others were treated only with a memory stent with a membrane, three of them with a large fistula （diameter 〉1.5 cm） were treated with bio-protein glue after placement of an esophageal metal stent. Results： The fistulas were covered by a stent and the patients could eat and drink immediately. Their quality of life was improved and their survival was prolonged, 44 out of 47 patients survived for 〉3 mo. Conclusion： Placement of esophageal stent with membrane or in combination with bio-protein glue through endoscope is an effective method for treating the bronchoesophageal fistula.

PROGNOSTIC FACTORS ANALYSIS FOR STAGEⅠ RECTAL CANCER

Objective: To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors including age, gender, tumor size, circumferential occupation, gross type, pathological type, depth of tumor invasion, surgical procedure, adjuvant chemotherapy and postoperative complication were chosen for cox multivariate analysis (forward procedure) using Spss software (10.0 version). Results: multivariate analysis demonstrated that muscular invasion was an independent negative prognostic factor for stageⅠrectal cancer patients (P=0.003). Conclusion: Muscular invasion is a negative prognostic factor for stage I rectal cancer patients.

TUMOR UPTAKE AND THERAPEUTIC EFFECT OF ASTATINATED INTACT McAb 3H11 AND ITS Fab FRAGMENT FOR HUMAN GASTRIC CANCER XENOGRAFT IN NUDE MICE

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Analysis of the Indicence and Survival of Female Breast Cancer Patients in Beijing Over a 20-Year Period

OBJECTIVE To provide evidence for breast cancer prevention and control through epidemiological analysis of the incidence, mortality and survival rate of female breast cancer patients in Beijing. METHODS The female registration data in the Beijing urban area from 1982 to 2001 were retrospectively reviewed. The incidence, mortality and survival rate of female breast cancer patients were analyzed using routine and life-table statistical methods. RESULTS During the period of 1982 to 2001, there was a trend of an average annual increase of female breast cancer incidence of 4.6% in urban Beijing, and of 4,9% in the world-population standardized incidence. The epidemiological features of urban Beijing female breast cancer showed：（1）The incidence distribution of different age groups from 25 to 80 years elevated with two peaks at ages of 45- and 70- years; （2）There was an elevation in each age group over the last 20 years; （3）The incidence rate at ages of 35 to 64 reached 95.3/10^5, causing breast cancer to become the number one cancer in females. The changes in the survival rate showed the following： the 5-year observed survival rate （OSR） increased from 62.0% in 1982～1983 to 68.7% in 1987-1988, and the relative-survival rate （RSR） increased from 6613% to 74.2%. The 10-year OSR and RSR in 1987～1988 were 60.3% and 65.1%, and at 15 years 57.5% and 61.3%, respectively. The mortality rate of breast cancer patients fluctuated from 8 to 10 per 105 population over the 20 years of study. CONCLUSION There is a trend of an annual increase in female breast cancer in Beijing. The 5-year survival is being improved gradually while the mortality remains stable. The results demonstrate that the principles of ＂early prevention, diagnosis and treatment＂ for breast cancer are effective in Beijing.

Changing patterns of colorectal cancer in China over a period of 20 years

AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients＇age at diagnosis, sex, the site of the tumor, stage, and the pathology. RESULTS： From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer （induding transverse and ascending colon） increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades. CONCLUSION： These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.

RELATIONSHIP AMONG CEA EXPRESSION IN TUMOR, CEA SERUM LEVEL AND RADIOIMMUNOGUIDED SURGERY IN COLORECTAL CANCER

Objective: To research the relationship among CEA expression in tumor, CEA serum level and Radioimmunoguided Surgery (RIGS) in Colorectal Cancer. Methods: twenty-nine patients with colorectal cancer wer administered radiolabeled McAb CL58 submucosally via endoscope, and all underwent surgical intervention 3 to 14 days later. Intraoperative radioimmunodetection was performed using a portable gamma-detecting probe (GDP). The counts of tumors were obtained, and tumor-to-normal tissue (T/NT) ratio was calculated. The T/NT ratio of 3:1 was taken as the lowest threshold value of positiveness. Anti-CEA immunohistochemical for all the samples were performed. The CEA serum levels of all the patients before operations were also recorded. Results: The sensitivity for RIGS in detecting primary lesions was 93.1% (27/29). 28 patients (96.6%) had CEA expressions to a greater or less extent. 5 patients (17.2%) had elevated CEA serum. There was no correlation between the CEA serum levels and results of RIGS (P>0.5), and no correlation between the CEA serum levels and CEA expression in tumor (P>0.5). The CEA expression in tumor correlated significantly with the RIGS results (P<0.05). Conclusion: This study indicates that immunostaining can be used to select the patients as candidates who will benefit most from RIGS.

THE CLINICAL SIGNIFICANCE OF TUMOR ANGIOGENESIS AND INVASIVENESS-RELATED GENE EXPRESSIONS IN GASTRIC CANCER

Objective: To investigate the correlation among tumor angiogenesis, expressions of p53, nm23-I1, CD44v6, c-erbB-2 proteins and biological behavior and clinical outcome of gastric cancer. Methods: The intratumoral microvessel density (MVD) and expressions of p53, nm23-H1, CD44v6, c-erbB-2 were analyzed semiquantitively by immunohistochemical staining (S-P) of 59 paraffin-embedded gastric tumor specimens that were radically resected at the Department of surgery, Beijing Institute for Cancer Research, between January 1990 and December 1992. The median follow-up period was 75 month (range: 60~96 months). The significdance of these indicators was analyzed retrospectively. Results: MVD for tumors with lymph node metastasis and vascular invasion was significantly higher than those without (P=0.0168 and 0.0176, respectively). The levels of p53, CD44v6, c-erbB-2 expression were significantly higher in the groups of lymph node metastasis, serosal infiltration and vascular invasion than in those without. All differences reached the statistically significant levels (P<0.01~<0.05). The low expression of nm23-H1 was negatively correlated with lymph node metastasis, serosal infiltration and vascular invasion (P<0.01; <0.05 and <0.01, respectively). Univariate analysis showed that the overall survival of patients with higher MVD, or overexpressions of p53, CD44v6, c-erbB-2, or low expression of nm23-H1 were significantly worse than those with opposite conditions (P=0.0214, 0.0062, 0.0045, 0.0159, and 0.0162, respectively). Multivariate analysis showed that expression of p53 in this series was an independent prognostic indicator. Conclusion: The data suggested that the above-mentioned factors might be helpful in evaluating the metastatic potential of gastric cancer and making more effective assessment of prognosis for individual patient. Further study with larger samples and prospective investigation of these results would be worthwhile.

THE SPECIFIC PHOTODYNAMIC EFFECTS OF MONOCLONAL ANTIBODIES CONJUGATED WITH HEMATOPORPHYRIN DERIVATIVE ON GASTRIC CANCER IN VITRO AND IN VIVO

Murine monoclonal antibody (MoAb) BB4.3, raised against the human gastric cancer cell line BGC823, was puriffied with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. It was then conjugated with a hematoporphyrin derivative (HPD) by using carbodiimide. The qualitative analysis of this conjugate showed that the amount of free HPD was negligible and there were no IgG aggregates among the conjugates. The conjugate retained both the antibody and photochemical activity of HPD.In vitro, the phototoxic effect of this HPD-BB4.3 conjugate on target cells was about 15 times higher than that of free HPD. The quality of selective photocytotoxicity was proven by the greater cytotoxi-city this conjugate showed than that of corresponding normal mouse IgG (NIgG) conjugated with HPD. It showed less cytotoxicity to colon cancer cell line B-80 (negative reaction to MoAb BB4.3) than to BGC825. Moreover, its cytotoxicity to BGC823 cells could be blocked specifically by excess BB4.3 antibody, but not by another MoAb 3G9, which combines with BGC823 at different binding sites from MoAb BB4.3.Nude mice inoculated with 2 × 10- BGC823 cells were given HPD-BB4.3, HPD, HPD-NIgG, HPD plus BB4.3 and PBS, respectively then exposed to light. Four out of six animals treated with the HPD-BB4.3 conjugate remained tumor-free for a long period. Although two developed tumors, there was a significant difference between the HPD-BB4.3-treated group and all the control groups in tumor induction time, tumor growth rate, and survival time (p<0.001). The HPD-BB4.3 conjugate inhibited the growth of established tumors by more than 40% in comparison with control groups (p<0.05).

THE UNILATERAL BIG HOCKEY STICK INCISION FOR NECK DISSECTION IN THYROID CARCINOMA

Objective: To investigate the feasibility and advantages of the unilateral big hockey stick incision in thyroid carcinoma. Method: Neck dissection using the unilateral big hockey stick incision was performed on 23 patients with thyroid carcinoma. Results: The big hockey stick incision results in a cosmetic scar which is barely visible and easily covered by hair or clothing, while it provides sufficient exposure of the operation field. A small area of marginal necrosis is occasionally seen at the apex of the skin flap due to preoperative radiotherapy. Conclusion: The unilateral big hockey stick incision has adequate surgical access, good healing of skin flaps, and a good cosmetic result.

HIGH INTENSITY FOCUSED ULTRASOUND FOR TREATMENT UNRESECTABLE MALIGNANT TUMORS IN 75 PATIENTS

Objective: To study preliminary experience of high intensity focused ultrasound (HIFU) for unresectable malignant tumors in 75 patients. Methods: The clinical data of 75 patients with unresectable tumor was analyzed retrospectively. Results: Among 75 patients, ten out of 57 cases achieved good local control in short-term, 5 patients liver tumor, 4 patients with tumor in the chest wall and one patient with bone matestics. Seven patients had skin burn and 2 patients developed intestinal perforations. Conclusion: HIFU is a novel tool for local tumor treatment. HIFU treatment for patients with unresectable tumor in the chest wall is effective.

MONOCLONAL ANTIBODIES AGAINST HUMAN GASTRIC CANCER

Spleen cells from Balb/c mice immunized with five human gastric cancer cell lines in sequence were fused with murine myeloma cell line SP2/0, and hybridomas 3F4, 3G9 and 3H11, secreting monoclonal antibodiees (MoAbs) against gastric cancer, were obtained through selective culture and screening. These MoAbs have both good selectivity and a high positive rate of reaction for gastric cancer, reaching 5/5 and 84.8% to 93.5% for gastric cancer cells and tissues respectively. The reaction of MoAbs with normal cells and tissues was neglible.The corresponding antigens of the MoAbs were sensitive to digestion by trypsin and pronase and resistant to treatment with sodium periodate, indicating their nature as proteins. The antigen 3G9 could be visualized with Western blotting as two bands with molecular weights of 100KD and 70KD, however no band was found for antigens 3F4 and 3H11. There was a high expression of antigens in the majority of gastric cancer cells and tissues independent of his-topathological type of gastric cancer. A low expression of antigens was seen with other tumors and fetal gastrointestinal tissues. These could be considered as gastric cancer-associated antigens or on-cofetal antigens with a quite extensive distribution.

HIGH-INTENSITY FOCUSED ULTRASOUND FOR TREATMENT OF UNRESECTABLE TUMORS LOCATED IN THE WALLS OF CHEST AND ABDOMEN IN 10 PATIENTS

Objective: To present our results of high-intensity focused ultrasound (HIFU) treatment in 10 patients with unresectable tumors involved in the walls of chest and abdomen. Methods: Tumors located in the walls of the chest and abdomen in 10 patients were treated by HIFU, including local recurrence of fibrosarcoma in 1 case and local invasion or metastases in 9 cases. All of the 10 patients had received anti-cancer treatments before HIFU, 3 patients were complicated with intercostal neuralgia. Results: Partial responses were obtained in 2 patients, minor response in 1 patient, stable disease in 4, progressive disease in 2 after HIFU treatments. All the intercostal neuralgia in 3 patients was disappeared after HIFU. Bone scan showed that site of rib metastasis before HIFU became normal after HIFU in one patient. Conclusion: Our preliminary results showed that HIFU could get good results for patients with malignant tumors located in the walls of chest and abdomen if they are focal tumors, even if they are complicated with rib metastasis.

PREOPERATIVE CHEMOTHERAPY OF CONTINUOUS INFUSION OF 5-FLUOROURACIL, EPIRUBICIN OR PIRARUBICIN AND CYCLO- PHOSPHAMINE IN OPERABLE PRIMARY BREAST CANCER

Objective: To evaluate the feasibility and activity of continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine as neoadjuvant regimen in patients with primary breast cancer. Methods: A total of 111 (including 114 breasts) were entered into the study. Chemotherapy consisted of two to six cycles of epirubicin 50 mg/(m2穌) and cyclophosphamide 500 mg/(m2穌) on day 1 and 8, and continuous intravenous administration of 5-fluorouracil 200 mg/(m2穌) from day 1 to 28 with a microinfusional elastomer (CEFci) or pirarubicin 35 mg/(m2穌) on day 1 and 8 instead of epirubicin (CTFci). Results: The overall response rate was 87.7%. Forty-five patients (39.5%) attained a complete clinical response and 27 (23.7%) attained a pathological complete response. CTFci regimen was superior to CEFci regimen in response rate,the pathological complete response rate (pCR) of former regimen was significantly higher than that of latter regimen (34.8% vs. 16.2%) (P=0.022). The pCR rate in ER/PgR negative tumor was significantly higher than that of ER/PgR positive tumor, achieving 33.3% and 7.5% respectively (P=0.001, x2=11.043). There was no relationship between HER-2 expression and tumor response. The toxicity of two regimens was well tolerated. Alopecia was mild in CTFci regimen comparing with CEFci regimen but neutropenia in CTFci regimen was higher than CEFci regimen. Conclusion: Continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine is effective regimens as neoadjuvant chemotherapy for primary breast cancer and the toxicity is well tolerated. Pirarubicin regimen was superior to epirubicin regimen in response rate.

EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

Objeetive： To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer （NSCLC）. Methods： Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results： Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion： Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

CARDIAC TOXICITY AFTER RADIATION THERAPY FOR 52 PATIENTS WITH MALIGNANT THYMIC TUMORS

Objective: To analyze the influencing factors for radiation-induced heart disease (RIHD) in a panel of cases with malignant thymic tumors treated by radiotherapy. Methods: 52 consecutive patients were treated by radiotherapy for malignant thymic tumor (14 at Masaoka stage II, 23 at stage III and 15 at stage IV). Treatment included radical (in 20), postoperative (in 14), preoperative (in 2) and palliative (in 16) radiotherapy. The conventional two-dimension (2D) radiation therapy was performed in forty-seven patients and three-dimension (3D) conformal radiation therapy has been used in 5 patients since October 2000. The total tumor dose ranged from 10 Gy to 84.5 Gy (median of 55 Gy). Chemotherapy was given in twenty-five patients before or after radiotherapy. The results of following-up could be obtained from the database and updated where appropriated. The dose volume histogram (DVH) of heart in radiotherapy for all patients was analyzed for the effective volume dose of heart. Result: The median following-up was 14 months (ranged from 0.6 to 111.3 months) in the study. RIHD was observed in seven patients. Cardiac toxicity of these seven patients were evaluated as SOMA grade 1-3. The median two-third effective volume dose of heart was 47.2 Gy (ranged from 8.3 Gy to 70.1 Gy) for conventional 2D radiotherapy, which correlated with thymic tumor dose (P<0.0001). The median two-third effective volume dose of heart was 35.3 Gy (ranged from 13 Gy to 38.7 Gy) for 3D conformal radiotherapy. The effective volume doses of heart were decreased by using 3D conformal radiotherapy (P=0.048). A significant association between cardiac toxicity and effective volume dose of heart was found in this study (P<0.0001). Cardiac toxicity accounted for 10.4% and 4.1% of patients receiving and not receiving adjuvant chemotherapy, respectively, and occurred earlier in radiochemotherapy group (P=0.0528). Multivariate analysis suggested that cardiac toxicity was significantly influenced by the effective volume dose of heart and chemotherapy. Conclusion: the results indicate that decreasing the effective volume dose of heart and carefully using chemotherapy drugs that have significant cardiotoxicity may reduce the probability of radiation-induced heart disease.

DETECTION OF p53 GENE MUTATION IN PLASMA OF PATIENTS WITH GASTRIC CANCER

Objective: To investigated p53 gene mutation in plasma of gastric cancer patients. Methods: DNA extracted from plasma and matched tumor and tumor-adjacent non-cancerous tissues of 96 gastric cancer patients, and DNA from 20 healthy volunteers were studied. Exon 5, 6, 7, and 8 of p53 were amplified by Polymerase Chain Reaction (PCR). The mutation status was analyzed by denaturing high-performance liquid chromatography (DHPLC), followed by direct sequencing of cases with aberrant chromatographic patterns. Results: Heterozygous mutations of p53 gene were detected in 19.9% (19/96) of primary tumor tissues and 5.2% (5/96) of corresponding plasma. All p53 gene mutations detected in plasma DNA consisted with mutations in the matched primary tumor samples. Neither the tumor-adjacent gastric mucosa tissues nor control plasma from healthy volunteers showed p53 gene mutation. No correlation was found between p53 mutation status and clinicopathological features of gastric cancer patients. Conclusion: p53 gene mutation in plasma can be detected in tissues and plasma of gastric cancer patients, which could be applied in screening and surveillance of this disease.

A study on the activation of 8 oncogenes and inactivation of 2 oncosuppressor genes in human gastric cancer

The changes of 8 oncogenes and 2 oncosuppressor genes in the specimens of cancer-ous and juxtacancerous tissues of 42 cases of gastric cancer were studied with southern blot hy-bridization and PCR-RFLP method.The probes used were c-Ha-ras,K-ras,N-ras,N-myc,c-myc,hst,EGFR,c-erbB-2,p53 and Rb.Amplification,rearrangement and deletion of c-Ha-ras were detected in 8/33 (24.2%) cases of gastric cancer,amplification or rearrangement ofhst and c-erbB-2 in 11/42 (26.2%) and 12/41 (29.2%) cases respectively,amplification ofEGFR in 9/42 (21.4%) cases,and deletion or rearrangement of p53 and Rb in 9/30 (30.0%)and 2/15 (13.3%) cases respectively.Amplification or rearrangement of N-ras (0/33),K-ras(1/26),N-myc (1/26),and c-myc (1/35)was rarely encountered.These findings suggest thatc-Ha-ras,hst,c-erbB-2,EGFR and p53 may be important genes involved in the pathogenesisof gastric cancer.