HEPATIC ARTERY CHEMOTHERAPY FOR COLORECTAL LIVER METASTASES

Fifty per cent of patients with colorectal cancer develop hepatic metastases but only a minority are candidates for potentially curative surgical resection. Hepatic artery chemotherapy (HAC) has been used to treat patients with non-resectable metastases confined to the liver. Although response rates to HAC have been shown to be higher thnn response rates to systemic chemotherapy. the advantage in ternis of survival has been dehated. Furthermore. HAC requires surgical catheter placement which adds to the cost and morbidity of treatment. There have now been eight prospective randomized trials of HAC vs intravenous chemotherapy and/or supportive therapy. The present paper analyses the results of these trials with particular reference to survival. Surgical morbidity. treatment-related toxicity and cost nre also discussed.     

PATTERNS OF SERUM CEA FALL AFTER HEPATIC ARTERIAL CHEMOTHERAPY AS SOLE THERAPY AND COMBINED WITH CRYOTHERAPY FOR COLORECTAL METASTASES

Background : Hepatic artery chemotherapy (HAC) and cryoablation are treatments for unresectable liver metastases from colorectal carcinomas. Our centre has previously published data that describe survival statistics of patients after each of these treatments. It has also been established that serial serum carcinoembryonic antigen (CEA) concentrations may be used to monitor disease progress, and that the magnitude of fall is prognostic for both treatments. The pattern of fall of CEA following cryotherapy and regional chemotherapy has not previously been compared. Methods : In this study, we examined 26 HAC patients and 24 cryotherapy patients. Results : The mean percentage of the pre-treatment CEA concentration for the HAC group was 60.5% at 50 days and 29.4% at 150 days, and for the cryotherapy group 24.9% at 50 days and 24.3% at 150 days. Calculating the difference between means revealed a significantly different mean fall in the cryotherapy group at 50 days (P < 0.001) and a difference in mean fall at 150 days (P > 0.1) which was not significant. In patients who responded to hepatic artery chemotherapy, the eventual CEA fall was very similar in magnitude. Conclusions: The pattern of fall of CEA differs in these two treatments.     

肝动脉、门静脉栓塞化疗治疗不可切除的原发性肝癌

目的：探讨肝动脉、门静脉双管栓塞化疗对不可切除的原发性肝癌的治疗作用。方法：对19例不可切除的原发性肝癌患者采用手术方法向肝动脉、门静脉植入皮下埋藏式投药泵,术中即开始经肝动脉投药泵栓塞化疗,术后7－10d在X线监测下经门静脉投药泵栓塞化疗,以后定期经两投药泵栓塞化疗,术后观AFP的变化、Bus或CT检查并与同期3次以上的32例HACE进行比较。结果：双栓化疗组17例术后1月AFP均下降、3月下降为正常8例,84．2％的肿瘤缩小,6月、9月、12月、24月生存率分别为89．5％、78．9％、68．4％、31．6％,中位生存期17．1月,其中2例进行了二期手术切除。HACE组术后1月AFP下降10例、3月后下降21例,46．9％的肿瘤缩小,6月、9月、12月、24月生存率分别为71．9％、53．1％、31．3％,中位生存期11．2月、12月、24月生存率组间比较P＜0．01;两组均无异位栓塞。结论：皮下埋藏式投药泵肝动脉、门静脉双插管栓塞化疗术后给药途径简单、方便、疗效好、并发症少,是治疗不可切除的肝癌有效方法之一。     

PRIMARY CEREBRAL LYMPHOMA: AN ARGUMENT FOR THE USE OF ADJUNCTIVE SYSTEMIC CHEMOTHERAPY

Eleven patients with primary cerebral lymphoma were treated at a single institution over a 5 year period. Patient characteristics were typical of this rare disease. One patient died prior to receiving treatment and of the remaining 10, all received cranial irradiation and in addition, five received systemic cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) chemotherapy. Of the six patients who are alive and disease-free, five received the combined modality therapy. The median survival for those patients receiving cranial irradiation alone was 18 months and for the combined modalities was 25+ months. Combination systemic chemotherapy, in addition to cerebral irradiation, may convey a survival benefit in patients with primary cerebral lymphoma but this requires further investigation with multicentre, prospective randomized trials.     

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). METHODS: Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m(2) on day 1; gemcitabine 1250 mg/m(2) on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m(2) on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. RESULTS: The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving > or = 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. CONCLUSIONS: Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC.     

选择性动脉化疗灌注联合微量泵输注治疗大肠癌

目的：对选择性动脉化疗灌注联合微量泵输注治疗大肠癌的价值进行探讨。方法：用Seldinger技术对31例大肠癌病例行选择性动脉灌注化疗药物（Mitomycin,Cisplatin)，保留导管，联合微量泵连续输注药物（Cisplatin Floxuridine)。结果：治疗后，患者临床症状改善明显，完全缓解1例，部分缓解23例，无变化6例，恶化1例，有效率77.4%,1,2,3年生存率分别为74.2%,54.8%与35.5%，其中9例于治疗2次后行根治性切除。结论：选择性动脉化疗灌注联合微量泵输注治疗大肠癌是一种安全有效的治疗方法。     

大肠癌术前动脉插管化疗与一般化疗的临床病理对比分析(附20例报告)

对２０例经病理确诊为大肠癌的病人行选择性动脉插管３种抗癌药一次性灌注治疗，其中１５例手术。切除标本用光镜观察癌细胞变性坏死的程度，并与病情相似、术前仅行一般化疗的１１例病人进行比较。结果显示：经本法治疗的病人除临床症状改善外，总有效率为１００％，而对照组有效率仅为１８．１８％，两组比较有高度显著性差异（Ｐ＜０．０１）。认为术前采用选择性动脉插管化疗可使癌灶缩小，提高手术切除率，减少术中医源性扩散及术后复发，对提高大肠癌病人的５年生存率有重要的临床意义。     

纯酒精与联合抗癌药治疗肝癌的疗效比较

选用纯酒精单用或联合抗癌药治疗原发性肝癌患者５３例，经２个疗程后，完全缓解１６例，部分缓解２１例，总有效率６９．８％，中位生存期１０．１个月。３种不同治疗方案中纯酒精联合阿霉素方案有效率较高（７８．６％），毒副反应主要为消化道反应及肝功能损害，但低于纯酒精联合多种抗癌药方案，故认为此方案在对不适合手术或不接受手术治疗的肝癌患者，可作为一种补救方法。     

PRE-OPERATIVE RADIOTHERAPY AND CHEMOTHERAPY FOR NON-RESECTABLE RECTAL CANCER

Background : The treatment results of combined pre-operative radiotherapy and chemotherapy followed by surgery for patients with initially non-resectable primary rectal cancer were reviewed. Methods : Thirteen patients with locally advanced non-resectable rectal cancer were treated with pre-operative irradiation consisting of 50.4–54 Gy plus concomitant 5-fluorouracil (5-Fu) delivered during the 1st and 5th weeks of radiotherapy. Results : Following pre-operative therapy, the resectability rate was 91%, with all but one patient undergoing complete resection. The pathologic complete response rate was 10%. The overall peri-operative and postoperative complication rate was 0.8 complications per patient. There was no postoperative mortality. Conclusions : This early experience indicates that high resectability rates are achievable with pre-operative radiotherapy and chemotherapy for non-resectable rectal cancer while maintaining acceptable postoperative morbidity.     

Long-term survival in locally advanced oral cavity cancer: an analysis of patients treated with neoadjuvant cisplatin-based chemotherapy followed by surgery

BACKGROUND: Neoadjuvant chemotherapy has been reported to be extremely active in head and neck cancer but has failed to give a statistically significant improvement in survival. METHODS: From 1981 to 1994, 33 operable patients with locally advanced oral cavity cancer received cisplatin-based chemotherapy before surgery. Postoperative radiotherapy was performed in high-risk patients. RESULTS: The overall clinical and pathologic complete response rates to neoadjuvant chemotherapy were 48% and 30%, respectively. At a median follow-up of 7.0 years (range, 0.3-15.3+ years), the 5-year and 10-year overall survival rates were 54.5% and 39.5%, and the disease-specific median survival was 6.6 years for all patients (8.3 and 2.3 years for stages III and IV, respectively). The univariate analysis showed a positive relationship between survival and male sex (p = .05), pathologic (p = .02), and clinical (p = .03) complete response. The Cox proportional hazard regression model confirmed the independent prognostic value of the clinical response with a 4.67 (95% CI, 1.70-12.86) hazard ratio. A second primary tumor occurred in six patients (18%), with a median of occurrence of 9 years (range, 7-11 years). CONCLUSIONS: This study confirms the prolonged survival expectancy largely exceeding 5 years for selected patients with stage IV and for most with stage III locally advanced oral cavity cancer achieving a clinical and/or pathologic complete response to chemotherapy.     

进展期胃肠道肿瘤术后联合化疗的临床疗效观察

目的:探讨进展期胃肠道肿瘤术后联合化疗的临床疗效。方法:自1994年1月至1999年12月我科对419例进展期胃肠道肿瘤根治术后的病例作了联合化疗。现就联合化疗对机体的耐受性、局部复发、腹腔种植转移、肝转移或其他远处转移和生存率的影响进行观察,并将之与同期行静脉化疗和腹腔化疗的病例进行分析比较。结果:联合化疗组病例的胃肠道反应、骨髓抑制和急性肾功能损害的发生率与腹腔化疗组相比无显著差异,但明显低于静脉化疗组(P<0.05)。静脉化疗组的肝转移和腹腔转移率(29.5%和32.8%)高于腹腔化疗组(14.2%和13.5%)和联合化疗组(12.8%和12.2%),而腹腔化疗组的其他远处转移率(18.4%)则远高于联合化疗组(11.5%)和静脉化疗组(9.8%)。联合化疗组病例的2、3、4及5年生存率分别为72.8%、65.1%、60.8%和55.2%,明显高于腹腔化疗组的59.2%、48.1%、43.8%和38.7%和静脉化疗组的58.9%、47.6%、42.9%和37.5%(P<0.05)。结论:进展期胃肠道肿瘤病人术后行联合化疗,降低了化疗的毒副反应,提高了病人的生活质量,有效地防止了病人术后的复发率和转移率,并延长了病人的生存期;是进展期胃肠道肿瘤根治术后较理想的化疗方式。     

Locally Advanced Breast Cancer: Is Surgery Necessary?

Abstract: A retrospective analysis of the treatment of locally advanced breast cancer (LABC) was undertaken at Stanford Medical Center to assess the outcome of patients who did not undergo surgical removal of their tumors. Between 1981 and 1998, 64 patients with locally advanced breast cancer were treated with induction chemotherapy, radiation with or without breast surgery, and additional chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was followed by local radiotherapy in 59 (92%) patients. Based on the clinical response to chemotherapy and patient preference, 44 (69%) patients received no local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin-containing chemotherapy in all patients. The mean age of patients was 49 years. Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph nodes only). Response to induction chemotherapy was seen in 59 patients (92%), with 29 (45%) achieving a complete clinical response and 30 (47%) a partial clinical response. With a mean follow-up of 51 months (range 7–187 months), 43 patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial 5-year survival is 75%, disease-free survival is 58%, and local control rate is 87.5%. These data indicate that the routine inclusion of breast surgery in a combined modality treatment program for LABC does not appear necessary for the majority of patients who experience a response to induction chemotherapy.     

Late results of postoperative long-term cancer chemotherapy for the gastric cancer patients subjected to curative resection

Postoperative long-term cancer chemotherapy (PLCC) with a combination of Mitomycin-C (MMC), FT-207 and PSK (an immunostimulant) was prescribed for gastric cancer patients subjected to curative resection. The 5 year survival rates for patients with stage III and stage IV cancer were 58.3 per cent and 50.0 per cent in the PLCC groups, 48.0 per cent and 15.4 per cent in MMC groups, and 46.3 per cent and 13.3 per cent in no chemotherapy groups, respectively. In stage IV, the survival rate in PLCC group was significantly higher than that in MMC or no chemotherapy group (p<0.05). In the PLCC group, there was a tendency toward a dose-dependent effect in each group, and 5 year survival rate of stage III group administered over 60 mg of MMC, 60 g of FT-207 and 270 g of PSK was 70 per cent, such being remarkably higher than 46.3 per cent in those given no chemotherapy (p<0.07). There was no drug related death and only a slight leukopenia and hepatotoxicity occurred in some patients.     

Histopathologic Evidence of Tumor Regression in the Axillary Lymph Nodes of Patients Treated With Preoperative Chemotherapy Correlates With Breast Cancer Outcome

Background: The benefits of primary tumor downstaging and assessment of chemoresponsiveness have resulted in expanded applications for induction chemotherapy. However, the pathologic evaluation and prognostic significance of response in preoperatively treated lymph nodes have not been defined.Methods: The axillary lymph nodes of 71 patients with locally advanced breast cancer treated with induction chemotherapy were evaluated for histological evidence of tumor regression as defined by the presence of nodal fibrosis, mucin pools, or aggregates of foamy histiocytes.Results: Complete pathologic response in the breast and axilla occurred in 10 patients (14%); 19 (26.8%) had evidence of tumor regression in 1 or more lymph nodes. Patients without nodal metastases and no evidence of tumor regression had the best outcome (median disease-free survival, 31.5 months; relapse rate, 27%). Patients with residual nodal metastases and no evidence of treatment effect had the worst outcome (median disease-free survival, 19.8 months; relapse rate, 55%). The median disease-free survival was 22.1 months, and the relapse rate was 32% for patients with histopathologic evidence of tumor regression in the axillary lymph nodes.Conclusions: Detection of treatment effect in axillary lymph nodes after induction chemotherapy identifies a subset of patients with an outcome intermediate between that of completely node-negative and node-positive patients. The axillary lymph nodes of patients receiving preoperative chemotherapy should be routinely analyzed for the presence of these features.     

Combination chemotherapy with ifosfamide, 5-fuluorouracil,etoposide and cisplatin for advanced urothelial cancer: the treatment results and significance of tumor marker evaluation in response assessment of chemotherapy

PURPOSE: We investigated treatment results of IFEPchemotherapy in patients with advanced urothelial cancer (N2-3, M1) and the usefulness of measuring serum CEA, CA19-9 and SCC to evaluate the treatment response of chemotherapy. PATIENTS AND METHODS: From March 1994 to May 2000, we treated 41 patients with IFEP therapy consisting of ifosfamide (2 g/m2), 5-fluorouracil (750 mg/m2), etoposide (100 mg/m2) and cisplatin (20 mg/m2), all of which were given daily for 3 consecutive days every 3 weeks. Before initiating the chemotherapy, serum CEA, CA19-9 and SCC were measured. And in patients with high pretreatment serum concentration, they were serially evaluated and compared with the tumor response assessed by imaging studies and the patients' clinical course. RESULTS: The response rate of the chemotherapy was 53.7% (CR + PR), with a median survival period being 10.8 months and a median duration of response for the 22 responders being 7.5 months. One and three-year survival rates of all the patients were 59.3% and 16.5%. Response rates of primary tumors and metastatic lesions to the lymph node, bone, lung and liver were in 54% and 57%, 56%, 50% and 40%, respectively. Bone marrow toxicity was significant with 1 drug-related death. Before chemotherapy, tumor marker was elevated in 19 patients: CEA in 7, CA19-9 in 13 and SCC in 10. Serum levels of the tumor markers were related neither to the primary and metastatic tumor sites nor to patient's survival time. However, decline of serum tumor markers after chemotherapy was well related to response of the tumor assessed by imaging studies. CONCLUSION: IFEP chemotherapy appears to be active in the treatment of advanced urothelial tumor and serial measurement of serum CEA, CA19-9 and SCC may be useful in judgement of tumor response to the chemotherapy.     

Results of Regional Chemotherapy Using the Aortic Stop-Flow Technique in Advanced Pancreatic Carcinoma

Purpose Systemic palliative chemotherapy provides only a disappointing response and almost no prolongation of the survival time in patients with pancreatic carcinoma. Isolated perfusion may lead to a higher concentration of cytostatics within the target tissue, which can be associated with a high response rate and longer survival in addition to a low rate of side effects. The aim of the study was to investigate the feasibility of the aortic stop-flow technique using commercially available tools in patients with advanced pancreatic carcinoma. Methods Seventeen patients with either unresectable or metastasized pancreatic carcinoma (diagnosed by histologic investigation) were enrolled in the study. In total, a 20-min hypoxic perfusion of the isolated abdominal compartment with 20 mg/m² of mitomycin C (Medac, Hamburg, Germany) was carried out 22 times. The cytostatic concentration was determined intrainterventionally within the systemic and regional compartment. The tumor response was assessed using computed tomography and a tumor marker (CA19-9) every 4 weeks. Results While 12 patients underwent one cycle, in 5 patients two complete perfusions were performed. Mitomycin C concentration was 10-fold higher within the regional compared with the systemic compartment at its maximum. The area under the curve (AUC) was 4.02 times larger. The degree of toxicity was considerable: World Health Organization grade I/II in 8/17, III/IV in 9/17 cases. Three treatment-related deaths were documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete remission [CR], 2 partial remissions [PR]). In 3 subjects, a stable disease (SD) and in 11 individuals tumor progression (PD) was registered. The median survival was 4.1 months. Conclusion The aortic stop-flow technique was associated with a high toxicity rate but no improvement in the tumor response and survival was seen in comparison to the systemic chemotherapy of the historical group. Despite detectable pharmacokinetic advantages, the aortic stop-flow technique is therefore not considered to be feasible for palliative chemotherapy in patients with pancreatic carcinoma for routine use.     

Postoperative long term chemotherapy for advanced gastric cancer

A postoperative long term chemotherapy was carried out against stage IV gastric cancer with Mitomycin-C, Futraful and a plant polysaccharide, PS-K. The 2-year survival rate was 15 per cent in patients who received an intraoperative Mitomycin-C alone, while it increased to 34 per cent in those receiving the anticancer agents for a prolonged period. The postoperative long term chemotherapy is assumed to be an effective means of improving the therapeutical results of gastric cancer.     

Prognostic factors for long-term survival in patients with locally invasive pancreatic cancer

Background/Purpose We aimed to investigate predictors of survival in patients with resectable locally invasive pancreatic cancer. Methods The patient cohort consisted of 55 patients with locally invasive pancreatic cancer (International Union Against Cancer [UICC] stage III in 36 patients and stage IV in 19) who had undergone resection. The patients were informed about the advantages and the adverse effects of postoperative chemotherapy, and prospectively selected either observation alone or postoperative chemotherapy. The postoperative chemotherapy regimen options were: (1) intraarterial chemotherapy alone, (2) systemic chemotherapy alone, or (3) intraarterial chemotherapy combined with systemic chemotherapy. Results Overall 1-year and 2-year survival rates after resection were 40.5% and 13.5%, respectively. Median survival time was 10.9 months. Twenty-nine patients (52.7%) received postoperative chemotherapy. On univariate analysis, only postoperative chemotherapy was associated with long-term survival (P < 0.01). In the patients with postoperative chemotherapy, the 1-year survival rate and MST were 61.7% and 16.3 months, compared with 20.1% and 7.9 months in the patients without postoperative chemotherapy. Multivariate analysis also showed that only postoperative chemotherapy was identified as an independent survival factor. Conclusions It was suggested that postoperative chemotherapy was essential for the improvement of survival in patients with locally invasive pancreatic cancer.     

胃癌术后腹腔化疗和静脉化疗的疗效比较

目的　比较进展期胃癌术后腹腔化疗和静脉化疗的临床疗效。方法　将 68例进展期胃癌术后化疗按前瞻、随机、对照的原则分为治疗组 (腹腔化疗 ) 3 3例及对照组 (静脉化疗 ) 3 5例 ,比较两组治疗的不良反应发生率、腹腔内复发率、肝转移率、3年生存率的差异。结果　治疗组胃肠反应率、骨髓抑制率、腹腔内复发率、肝转移率、3年无瘤生存率、3年生存率分别为 12 .1%、9.0 %、18.1%、12 .1%、2 3 .6%、5 4.5 %。对照组胃肠反应率、骨髓抑制率、腹腔内复发率、肝转移率、3年无瘤生存率、3年生存率分别为 91.3 %、85 .7%、60 .0 %、3 7.1%、12 .8%、3 4.3 %。结论　与静脉化疗比较 ,进展期胃癌术后腹腔化疗的不良反应发生率、腹腔内复发率、肝转移率、3年生存率率降低 ,差异有显著性 (P <0 .0 5 )。     

Resecting large numbers of hepatic colorectal metastases

Background : Despite the widespread use of surgical resection as a treatment for hepatic colorectal metastases, the value of resecting more than three metastases remains controversial. It was the objective of this study to determine if resection of larger numbers of metastases affects patient survival. Method : The survival of 123 consecutive patients who underwent curative hepatic resection for colorectal metastases between 1989 and 1999 by a single surgeon was analysed retrospectively. Kaplan–Meier survival statistics and Cox regression were used to determine the factors that affected survival, and logistic regression was used to determine the factors that affected the risk of recurrence of hepatic disease. Results : The median survival rate for the whole group of patients was 38 months, with 1, 3 and 5 year survival rates of 88%, 53% and 31% respectively. The survival rate of patients undergoing resection of four to seven metastases (n = 22; 5 year survival = 39%) was not significantly different to that of patients undergoing resection of one to three metastases (n = 91; 5 year survival = 30%), P = 0.9. Age, sex, primary cancer site, hepatic disease distribution, resection margins and adjuvant hepatic arterial chemotherapy (HAC) did not affect survival. Local invasion of the hepatic metastases (relative risk (RR) = 2.9; P = 0.001) and hepatic disease recurrence (RR = 2.1; P = 0.007) were the only factors that independently affected survival. Local invasion of the hepatic metastasis was the only factor associated with an increased risk of hepatic recurrence (RR = 2.8; P = 0.03). Adjuvant HAC did not affect the risk of hepatic recurrence (RR = 1.5, P = 0.4). Conclusion : Although there are no randomized trials that quantify any survival benefit from resection of liver metastases, the comparison of our results with well documented historical evidence indicates that surgical resection of up to seven colorectal liver metastases can result in a significant survival benefit.