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。     

Treatment of medulloblastoma in children: Long-term results following surgery,radiotherapy and chemotherapy

Summary Forty-seven children with histologically confirmed medulloblastoma are considered. Forty-five cases were surgically treated by direct approach to the tumour, while two cases were treated only with a shunt. A shunt was inserted preoperatively in 14 cases, postoperatively in 4 cases. Surgical resection was total or subtotal in 52% of cases, partial in 35%, and limited to a biopsy in 13%. Radiation treatment to the entire neuraxis was done in 37 cases: 10 of these cases received additional chemotherapy—mostly with CCNU—as primary treatment for medulloblastoma.Ten patients died within 30 days after surgery. Twenty-two patients died months after treatment, mainly from tumour recurrence (19 cases). One patient was lost to follow-up. Thirteen patients are survivors from 10 months to 20 years after treatment. As a whole, the one year survival rate has been 67%, 3 year survival 43%, and 5 year survival 27%. Complications affecting prognosis have been presented by tumour recurrence and metastases. CSF shunting and lack of prophylactic irradiation to the cerebral hemispheres have been considered responsible for the high incidence of supratentorial metastases in our series.Factors influencing prognosis have been the extent of tumour resection and association of primary chemotherapy with radiotherapy. Within 3 years after surgery survival has been 52% in cases with total resection against 31% in cases with partial resection of tumour. As regards chemotherapy, 3 year survival has been 60% for patients with combined treatment (chemo- and radiotherapy) against 37% in patients with radiotherapy alone. It is concluded that the best results in children with medulloblastoma are achieved by a radical resection, associated with a combined primary treatment of radiotherapy and chemotherapy.     

Prognostic Factors in Gastric Carcinoma with Peritoneal Dissemination

Objective: The prognosis for gastric carcinoma patients with peritoneal dissemination is very poor. We evaluated the survival benefit of resection and intravenous chemotherapy in these patients.

Material and methods: We reviewed the hospital records of 348 gastric carcinoma patients with peritoneal dissemination seen during the period from 1986 to 2000.

Results: Based on the grade of anaplasia, 76 (21.8%) were differentiated and 272 (78.2%) were undifferentiated. In the univariate analyses, the factors influencing the 5-year survival rate were histologic type, resection, and intravenous chemotherapy. Using Cox’s proportional hazard regression model, two factors were independent, statistically significant prognostic parameters: resection (risk ratio, 1.48; 95% confidence interval, 0.90-2.46; p<0.05) and intravenous chemotherapy (risk ratio, 1.68; 95% confidence interval 1.15-2.47; p < 0.01). The 5-year survival rate was higher for patients who had intravenous chemotherapy (3.6%) than for patients who did not (2.4%), and also higher for patients who underwent resection (4.8%) than for patients who did not (0%; p < 0.001).

Conclusion: The results highlight the improved survivorship of gastric carcinoma patients with peritoneal dissemination who had resection and received intravenous chemotherapy, compared with those who did not. Although curative resection cannot be performed in this group of patients, we recommend performing resection and subsequent intravenous chemotherapy.     

肝动脉化疗栓塞治疗胃癌肝转移的临床疗效

目的评价肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE）治疗胃癌肝转移的临床疗效、毒副反应及生活质量的改善情况。方法收集31例同时性胃癌伴肝转移患者的临床资料,行TACE治疗。结果全组患者完全缓解（CR）4例,占12.9%;部分缓解（PR）17例,占54.8%;病变稳定（SD）6例,占19.4%;病变进展（PD）4例,占12.9%,总有效率（CR＋PR）为67.7%。结论针对胃癌肝转移患者,TACE治疗是有效的。     

结直肠癌肝转移手术切除及全身、区域化疗

结直肠癌肝转移发病率高,是结直肠癌的常见死亡原因。其主要治疗方法有手术切除和全身化疗与区域化疗,而手术切除是提高存活率的关键。目前,结直肠癌肝转移以手术治疗为核心的综合治疗体系已经形成,然而,手术切除与全身、区域化疗的科学选择是进一步提高该类病人存活率和使病人获得最大收益的关键。     

结直肠癌肝转移术前药物治疗进展

正肝脏是结直肠癌转移最常见的靶器官,50%的结直肠癌病人会在其病程中出现肝脏转移,2/3的结直肠癌病人因为肝脏转移而死亡。手术仍是结直肠癌肝转移(colorectal cancer liver metastases,CRLM)病人获得治愈的惟一方法~[1],5年存活率50%,且有20%的病人存活10年。但是80%的CRLM病人初诊时为不可切除,且肝切除术后1年内复发率为30%~47%~[2-3]。多学科综合治疗协作组(multidis-     

Chirurgische therapie von lebermetastasen therapieverfahren,ergebnisse und prognosefaktoren

Zusammenfassung In einem Zeitraum von 7 Jahren wurden 151 Patienten mit Lebermetastasen verschiedener Primartumoren durch Leberresektion and/oder regionale Chemotherapie behandelt. Aufgrund der Heterogenität and geringen Zahl der übrigen Primartumoren wurden Patienten mit kolorektalem Karzinom gesondert betrachtet. Die beste Prognose wurde durch eine potentiell kurative Resektion mit einer 5-Jahres-Überlebensrate von 17% erzielt. Einziger signifikanter and unabhängiger Prognoseparameter war neben der Radikalität das Intervall zwischen Primärtumoroperation and Auftreten der Metastasierung. Durch eine adjuvante regionale Chemotherapie konme kein zusätzlicher Prognosegewinn nach kurativer Resektion erzielt werden. Die alleinige regionale Chemotherapie bei diffuser hepatischer Metastasierung führte ebenso wie die additive regionale oder systemdsche Chemotherapie nach palliativer Leberresektion zu keiner signifikanten Verlängerung der Überlebenszeiten.

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Surgical treatment of liver metastases Treatment methods, results and prognostic factors

In a period of 7 years, 151 patients were treated by resection and/or regional chemotherapy after liver metastases from various primary tumours. The subgroup of patients with colorectal liver metastases was evaluated separately from the heterogeneous group with any other primaries. Radical resection of colorectal liver metastases was followed by a 5-year survival of 17%. The time from resection of the primary to development of the metastatic lesions was shown by univariate and multivariate analysis to be the most important prognostic factor. Adjuvant regional chemotherapy failed to improve outcome after curative resection of liver metastases. Neither palliative regional chemotherapy in cases of diffuse hepatic metastases nor the combination of palliative resection with regional or systemic chemotherapy significantly prolonged survival.

     

Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration

Study Type – Therapy (multi‐insititutional cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Neoadjuvant chemotherapy offers survival benefits for patients with urothelial carcinoma of the bladder. However, it is still underutilized in the ‘biologically similar’ upper tract urothelial carcinoma. Systemic chemotherapy in a neoadjuvant setting is a more attractive option, as loss of renal function after nephrectomy can complicate the administration of adjuvant chemotherapy. We found that preoperative systemic therapy followed by aggressive surgical debulking is a promising treatment strategy for upper tract urothelial carcinoma patients with known or at risk of loco‐regional nodal metastasis.

OBJECTIVE

? To describe a multicentre experience with preoperative platinum‐based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco‐regional nodal metastases.

PATIENTS AND METHODS

? We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. ? Group 1 comprised patients who received chemotherapy before RNU because of biopsy‐proven loco‐regional nodal metastases. ? Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node‐positive). ? Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node‐negative (N0) UTUC.

RESULTS

? Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5‐year disease‐free survival rates were 49%, 30% and 64%, whereas the 5‐year cancer‐specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. ? In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan–Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). ? Meanwhile, group 2 had significantly lower disease‐free and cancer‐specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively).

CONCLUSIONS

? Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco‐regional nodal metastases. ? These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.     

The Role and Limitations of 18-Fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

Background Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. Methods Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. Results Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). Conclusions FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory. The abstract was presented before the 58th Cancer Symposium of the Society of Surgical Oncology, Atlanta, GA, USA, 2005, and before the 2005 Congress of the American Hepato-Pancreato-Biliary Association, Fort-Lauderdale, FL, USA.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

Background: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. Methods: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. Results: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P<.05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. Conclusions: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–28, 1998.     

Resection of liver metastases from colorectal cancer – how can we improve results?

Resection of liver metastases due to large bowel cancer has become an important part of treatment. In recent years, there have been advances in technique and the selection of patients has been extended. Surgery is the only modality which currently offers the possibility of long‐term survival. Resection combined with chemotherapy may offer improved survival, but more data are needed. Chemotherapy may cause regression of metastases to permit resection where initially they were considered unresectable. The data available from such studies are presented.     

Results of surgical treatment for multiple (≥5 nodules) bi-lobar hepatic metastases from colorectal cancer

Background The surgery for the treatment of multiple (5) bi-lobar hepatic metastases from colorectal cancer is controversial. This retrospective study presents our experience in an attempt to develop reasonable treatment guidelines.Method One hundred sixty-one consecutive patients who underwent liver resection with curative intent were classified into three groups: H1 (unilateral), H2 (bilateral, 4 nodules), or H3 (bilateral, 5 nodules).Results The overall cumulative 5-year survival rate was 46.7%. Survival was similar among patients with H1, H2, and H3 disease. Thirty-two patients with H3 disease underwent hepatectomy: straightforward hepatectomy in 12, portal vein embolization (PVE) prior to hepatectomy in eight, two-stage hepatectomy in two, and two-stage hepatectomy combined with PVE in ten. Two-stage hepatectomy with or without PVE was the standard approach in patients with synchronous liver metastases. The operating mortality in hepatectomy for H3 disease was 0%, and the morbidity was 15.2%. The overall response rate to neoadjuvant chemotherapy (NAC) was 41.7% (5/12). Patients who responded to NAC (n=5) had a better prognosis than non-responders (n=7) (P<0.05).Conclusions Extended hepatectomy, including preoperative PVE and multi-step hepatectomy, combined with NAC, may result in a favourable prognosis, especially in patients who respond to NAC, but further studies with more patients are needed to confirm this.     

同时性结直肠癌肝转移治疗策略

正同时性结直肠癌肝转移(colorectal cancer with synchronous liver metastases,s CRLM)的治疗,涉及化疗、手术、射频、介入等,对于直肠癌还涉及放疗,化疗又有新辅助、转化、辅助之分,手术也涉及胃肠道及肝脏,有同期切除、分期切除、切除顺序等问题,可以说s CRLM是整个外科中最为复杂的疾病。相比于其他伴有同时性转移的肿瘤来说,s CRLM的发病率高、预后好,手术后5年存活率可达到     

Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: Interim results of a phase I trial

Background: Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensity therapy without associated toxicity. Methods: The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC. Results: In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients. Conclusions: This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.Results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

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.     

Hepatic Arterial Infusion and Systemic Chemotherapy for Breast Cancer Liver Metastases

Hepatic failure from breast cancer liver metastases (BCLM) is a major cause of morbidity and mortality. We reviewed the treatment histories and outcomes of nine patients with heavily treated BCLM, who received hepatic arterial infusion (HAI) of floxuridine (FUDR)/dexamethasone (Dex) and systemic chemotherapy at our institution. Patients received a median of five (range 1–15) HAI treatments. There were seven (78%) objective responses. Four patients had grade 3 elevations in liver enzymes attributable to HAI. There were no treatment‐related deaths. Median hepatic and extrahepatic time to progression on HAI were both 6 months. Median survival after starting HAI was 17 months (range 1–115). Median overall survival from the original breast cancer diagnosis was 110 months (range 52–248). One patient is alive with stable disease on systemic therapy alone. HAI and systemic chemotherapy is feasible and can benefit selected patients with BCLM, who have progressed on prior therapies. Patients require close monitoring for treatment‐limiting toxicities.     

The enhanced therapeutic efficacy of intra-arterialCis-diamminedichloroplatinum (II) chemotherapy in combination with aortic clamping on metastatic hepatic tumors in the rat

The efficacy of intrahepaticcis-diamminedichloroplatinum (II), cisplatin, administered via the hepatic artery in combination with concomitant clamping of the abdominal aorta beneath the diaphragm against metastatic liver tumors in rats was evaluated. When 2.5 or 5 mg/kg of cisplatin was injected intra-arterially (i.a.) over 5 min, the antitumor activities in the rats with aortic clamping, evaluated by the number of tumor nodules and survival days after treatment, were found to be superior to those in the rats without aortic clamping. Side effects, evaluated in terms of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels, changes in body weight, and the number of leukocytes, did not differ significantly among the rats with or without aortic clamping. The blood urea nitrogen levels observed in the rats with aortic clamping were lower than in those without aortic clamping. Immediately after the injection of cisplatin 5 mg/kg i.a., the platinum concentrations in the livers of rats with aortic clamp-platinum concentrations in the livers of rats with aortic clamping were approximately 2.1 times higher than in those without aortic clamping, and 1.4 times higher even 60 min after the injection. These increased platinum concentrations in the liver explain the enhanced antitumor activities of the rats given cisplatin with aortic clamping.     

Relevance of neoadjuvant and adjuvant treatment for patients with resectable liver metastases of colorectal carcinoma

Background: Excellent results after resection of colorectal liver metastases are associated with a high rate of recurrence. Influenced by positive results of palliative and adjuvant treatment in advanced cancer, various chemotherapy regimens were evaluated to improve long-term results. Methods: The databases Medline and Cancerlit (1982–1998) gave information about 675 patients who were treated either by means of systemic, intra-arterial, intraportal or intraperitoneal administration before or after liver resection. Results: In general, the feasibility of an adjuvant treatment was tested. Proof has been furnished for the practicability of systemic and arterial therapy and for immunotherapy after liver resection whereas, for peritoneal and portal treatment, further studies are necessary. In a few non-randomised trials, it has been possible to discern a trend towards an improvement due to adjuvant postoperative therapy using historical or matched-pair control groups. Until now, only one of five randomised studies has been published. Six months of postoperative adjuvant intra-arterial treatment using 5-fluorouracil (1000 mg/m² for 5 days every 28 days) and folinic acid (200 mg/m² for 5 days every 28 days) was compared with observation only. Neither in the intention-to-treat nor in the as-treated analysis was median survival time (34.5 months versus 40.8 months and 39.7 months versus 44.8 months, respectively) significantly increased. As neoadjuvant treatment was successful in primary non-resectable patients, this approach is now being tested in resectable patients. Conclusion: Despite several theoretical reasons for post- or preoperative treatment in resectable patients, every approach should be tested using of controlled studies. Received: 2 March 1999 Accepted: 28 June 1999