Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases. Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis. Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients; metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous and metachronous cases. Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases. Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining candidates for surgery and in selecting surgical procedure.     

Validity of observation interval for synchronous hepatic metastases of colorectal cancer: changes in hepatic and extrahepatic metastatic foci

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer maintains a strong influence on the metastases, so the possibility of occult hepatic and extrahepatic metastases must be kept in mind. Our treatment policy has been to reevaluate the metastases at an interval of 3 months after colorectal resection and determine treatment strategy. We examined the validity of observation interval for synchronous hepatic metastases. Materials and methods The treatment course was investigated for 36 patients with no extrahepatic lesion remnants at colorectal surgery and a simultaneously resectable liver (H1 group). Results In the H1 group, eight patients underwent simultaneous colorectal and hepatic resections, while the treatment course for 28 patients was decided after an interval. Hepatic resection was not indicated in nine of the 28 patients during the interval. New lesions appeared during the interval in seven of 19 interval hepatic resection patients. In 16 (57%) of 28 interval patients, there was a change in the hepatic resection procedure or surgical indications. Conclusion Reevaluation after an observation interval allows accurate understanding of the number and location of hepatic metastases and is beneficial in determining candidates for surgery and in selecting treatment plan.     

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.     

Repeat hepatic cryotherapy for metastatic colorectal cancer

This study evaluated the risks and benefits of repeat hepatic cryotherapy for recurrent, unresectable hepatic metastases from colorectal carcinoma. Review of a prospective database identified 195 patients who underwent hepatic cryotherapy for metastatic colorectal carcinoma during a 7-year period. Of the 14 patients who underwent successful repeat cryotherapy for recurrences confined to the liver, 86% had Duke’s stage D colorectal carcinoma at initial diagnosis. The median age of the 14 patients was 58 years (range 41 to 77 years). The median number of hepatic metastases was three at the first cryotherapy and two at the second cryotherapy. At a median follow-up of 71 months, the mean survival times from original diagnosis, first cryotherapy, and second cryotherapy were 53,42, and 19 months, respectively. At the most recent follow-up, eight patients (57%) have died of their disease, four (29%) are alive with disease, and two (14%) have no evidence of disease. The mean interval between the first and second cryotherapies was 23 months. The complication rates after the first and second cryotherapies were 7% and 14%, respectively. One patient developed a wound dehiscence after the first cryotherapy. Following the second cryotherapy, one patient had a small bowel obstruction and another had a pleural effusion. There was no perioperative mortality. Repeat cryotherapy for recurrent, unresectable hepadc metastases from colorectal cancer is safe and improves survival. However, a prospective trial is needed to validate the efficacy of systemic therapy and to better define the indications for repeat hepatic cryotherapy. Supported in part by grant T32 CA 09689 from the National Cancer Institute and by funding from the Rogovin-Davidow Foundation, Los Angeles, Calif. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 2l–24, 2000.     

Repeat hepatectomy for colorectal metastases

The utility of repeat hepatectomy for patients with colorectal metastases to the liver was sought. A complete review of the results of surgical treatment of patients having a repeat hepatectomy was presented. Then, the data on 170 patients in whom multiple clinical variables had been tabulated were selected for special study. These statistical analyses showed that there were no special clinical features present at the time of primary resection of the large bowel cancer that could distinguish these patients. There were some differences in the clinical features of these patients at the time of first and second liver resections. The disease-free interval, method of diagnosis, presence of extrahepatic disease, incidence of complete resection, and postoperative morbidity showed significant differences. The 5-year survival of the group as a whole was 32%. Only those clinical features which involved the completeness of cancer resection had a significant impact on survival. To optimize selection for a long-term survival, no extrahepatic disease should be present and the second hepatectomy should involve removal of all visible tumor. Repeat hepatectomy for colorectal metastases was thought to be justified if the patient was made clinically disease-free, because surgery remains the only potentially curative treatment. The repeat hepatectomy was relatively safe with a low morbidity and conferred a 32% long-term survival. Received for publication on Aug. 30, 1998; accepted on Nov. 2, 1998     

Imaging strategies in hepatic metastases from colorectal carcinoma

Approximately two-thirds of metastatic lesions that develop following curative resection of colorectal cancer occur in the liver and lung. In select groups of patients, resection of these lesions is associated with increased 5-year survival. In the liver, precise preoperative documentation of the presence, location, number, and relationship of these lesions to vascular structure is crucial in the selection of candidates for curative resection. Computed tomography with arterial portography (CTAP), intraoperative ultrasonography (IOUS), positron emission tomographic (PET) scan, and radionuclide scanning, including radiolabeled monoclonal antibody imaging, are emerging as the procedures of choice in the preoperative and intraoperative evaluation of metastatic colorectal cancer to the liver.     

大肠癌肝转移的诊断及外科治疗

目的：总结和分析大肠癌肝转移的早期诊断和手术治疗。方法：通过对大肠癌肝转移病例进行回顾性分析,讨论大肠癌的早期诊断及外科手术切除治疗等相关问题。结果：18例中,依靠CT、B超及CEA定量检测获得诊断者10例,术中探查获得诊断者8例。手术方式分为肝段切除、肝楔形切除及肿瘤剜出术。生存5年者2例,生存4年者3例,生存3年者5例,生存2年者5例,生存1年者3例。结论：手术治疗是大肠癌肝转移最有效 的治疗方法,主流术式应为不规则肝切除,切缘距肿瘤＞1．0cm为大肠癌肝转移的根治性切除术。     

结直肠肿瘤肝转移的外科治疗

目的 探讨结直肠肿瘤肝转移的外科治疗意义。方法 回顾性分析经手术切除和病理证实的39例结直肠肿瘤肝转移患者的临床资料。结果 全组无于术死亡．均治愈出院。随访37例，存活时间6个月～4年。结论 对于结直肠肿瘤肝转移有适应证的患者手术有明确的疗效。     

Treatment strategy for multiple hepatic metastases of colorectal carcinoma

We describe the treatment strategy for multiple hepatic metastases of colorectal carcinoma based on a review of the literature and our own results. Although a number of studies have suggested that multiplicity or bilobar distribution of metastases is associated with poor outcome, liver resection is thought to be the only potentially curative treatment. The only contraindications to surgery are the presence of extrahepatic metastases (with the exception of resectable lung metastases) and if radical removal of all detectable tumors is not possible. Hepatectomy should be performed with the aim of maintaining a delicate balance between radical removal of tumors and the preservation of as much residual hepatic mass as possible with minimal blood loss. Surgeons should be familiar with the use of intraoperative ultrasonography, a standard adjunct to liver resection. Preoperative portal vein embolization may be indicated in selected patients as a means of inducing hypertrophy in the remaining hepatic parenchyma. Received for publication on Aug. 30, 1998; accepted on Nov. 2, 1998     

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Follow-up report

Single institution studies of hepatic resection have implied that some subsets of patients with metastases from colon and rectum adenocarcinoma can be cured by surgery. However, it is unknown how such patients can be selected and what, in fact, the ultimate cure rate is. The objective of this multi-institutional study was to define in a prospective manner how many patients predicted to have resectable liver metastases actually could undergo curative resection and what the disease-free and overall survival were. A prospective 15-institution treatment plan included all patients who were predicted to have resectable metastases from colon and rectum cancer primaries. Results were compared among patients who underwent successful resection, patients who underwent resection with pathologically defined inadequate margins, and patients who underwent exploration but were found at surgery not to have resectable liver metastases. Fourteen institutions throughout North America and one in Milan who were members of the Gastrointestinal Tumor Study Group at the inception of this protocol in July of 1984 participated in the study. The patient population consisted of all those with metachronous or synchronous metastases from colon or rectum adenocarcinoma seen during a consecutive 3 1/2 year period with protocol registry at the time liver metastases were predicted to be isolated and resectable. Intervention consisted of the application of standard preoperative screening tests, abdominal exploration, and resection of all patients who had liver-only surgically resectable disease. The main outcome measures were: Accuracy of preoperative staging, acute and chronic operative morbidity, and disease-free, as well as overall, survival among the three treatment groups. The minimum follow up on all surviving patiens after curative resection was 2.2 years, with a median follow up of 3.2 years. Median survival times for patients receiving curative and noncurative resections and for those receiving no resection were estimated to be 35.7, 21.2, and 16.5 months, respectively. No statistically significant difference in the survival distribution of the noncuratively resected or the non-resected patients was observed. The survival distribution of curatively resected patients remains statistically superior to the distribution of noncuratively resected patients and those receiving no resection (P=0.01). These results confirmed that, although liver resection for hepatic metastases from colorectal car cinoma is safe to do and presently constitutes the only standard curative treatment for potentially resectable disease, it ultimately cures few patients.     

Repeat hepatic resection as effective treatment for recurrent colorectal liver metastases

Background: Approximately 20–40% of patients who undergo liver resection for colorectal metastases develop recurrent disease confined to the liver. The goals of this study were to determine whether the survival benefit of repeat hepatic resection justified the potential morbidity and mortality. Methods: A retrospective review was performed on all patients who underwent liver resection for colorectal cancer metastases between 1983 and 1995 (N=202). Repeat liver resections were performed on 23 patients for recurrent metastases. Results: There were no operative deaths in the 23 patients, and the postoperative morbidity rate was 22%. The 5-year actuarial survival rate after repeat resection was 32%, with a median length of survival of 39.9 months. There were three patients who survived for >5 years after repeat resection. Sixteen patients (70%) developed recurrent disease at a median interval of 11 months after the second resection; 10 of these 16 patients (62%) had new hepatic metastases. No clinical or pathological factors were significant in predicting long-term survival. Conclusions: Repeat liver resection for recurrent colorectal metastases (a) can be performed safely with acceptable mortality and morbidity rates and (b) may result in long-term survival in some patients.Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m², using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm³ in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.     

Surgical resection for pulmonary metastases from colorectal cancer

Background : Isolated pulmonary metastases from colorectal cancer are rare. The present study reports on the 15‐year experience of the Royal Prince Alfred Unit and discusses means of improving survival outcomes. Methods : This was a retrospective review, over a 15‐year period, of 41 patients who had resectable pulmonary metastases of colorectal origin. Results : Most were asymptomatic at the time of diagnosis. Seventy‐two per cent had solitary metastases. The most common procedure performed was a lobectomy. Median follow up was 21 months. Five‐year survival was 24%. There were no significant prognostic indicators except for the ability to achieve clear surgical margins. Conclusion : Morbidity and mortality have not altered significantly over time. But an improved selection process such as the use of preoperative positron emission tomography will potentially improve survival outcomes.     

Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer

The inhibitory action of prostaglandin D₂ (PGD₂) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24h and 48h after the addition of 1.0μg/ml and 10.0μg/ml PGD₂. The growth of SW480 cells and 24h and 48h after the addition of 10.0μ/ml, while that of LS174T was inhibited by both doses after 24h and 48h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24h after the addition of 10.0μg/ml PGD₂. The cell cycle of LS174T cells was arrested at the G₀+G₁ phase 24h after the addition of 1.0μg/ml and 10.0μg/ml PGD₂. The correlation between hepatic metastasis and PGD₂ concentration in human cancer tissue was examined. The mean value of PGD₂ concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD₂ in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.     

电穿击化疗治疗异位移植裸小鼠人结直肠肿瘤肝转移

目的 :用电穿击化疗对异位移植裸小鼠人结直肠肿瘤肝转移模型进行治疗 ,探讨其疗效和机制。方法 :将 4 0只皮下人结肠癌LoVo细胞系肿瘤的裸鼠随机分成 1 0区组 ,每区组 4只 ,随后将每区组的小鼠分至电穿击化疗组、化疗组、电击组、阴性对照组 ,并给予相应的治疗。 1w后处死小鼠 ,观察瘤重及病理改变情况。结果 :电穿击化疗组小鼠的肿瘤显著减小 ,其中有一只小鼠的肿瘤完全消失 ,平均瘤重为 1 8.3mg ,与其余各组平均瘤重 (化疗组 36 .9mg、电击组 37.9mg、阴性对照组 4 2 .7mg)相比在统计学上差异有显著性 ,P<0 .0 1。光镜下可见电穿击化疗组的肿瘤组织有大量片状坏死、炎性细胞浸润、血管的扭曲及内皮的脱落和坏死 ,而化疗组和电击组则仅见少量炎性细胞的浸润和单个细胞的坏死。结论 :电穿击化疗可以显著增强肿瘤对化疗的敏感性 ,为人结直肠肿瘤肝转移的治疗提供了一种新的途径     

Paratesticular metastasis from colorectal adenocarcinoma

Paratesticular tumors are rare, especially when they are metastatic. Most of them originate in the prostate, kidney, gastrointestinal tract, lung, and breast. The most common site of metastasis from the gastrointestinal tract is the colon. A 75-year-old male presented with a painless and tense right scrotal mass. He underwent a radical right orchiectomy, and the pathology revealed mucinous cystadenocarcinoma of the paratesticular tissue. Computed tomography revealed focal wall thickening at the rectosigmoid junction and liver nodules. The colonoscopic biopsy of the mass showed adenocarcinoma. Immunohistochemical staining of both sites confirmed the diagnosis of colorectal adenocarcinoma metastatic to the scrotum.     

The routine use of intra-operative ultrasound in patients with colorectal cancer improves the detection of hepatic metastases

INTRODUCTION: Up to one fifth of patients with carcinoma of the colon have occult liver metastases at the time of presentation. Intra-operative hepatic ultrasonography might improve disease staging. We report the use of intra-operative ultrasonography (IOUS) in routine clinical practice over a five-year period. METHOD: Seventy-six patients with colorectal carcinoma (F 21, M 55) of median age 67 years (range 43-89 years) for whom full data were available had IOUS at the time of colonic resection. All patients had had a computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS). RESULTS: Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C carcinoma. In 20 patients IOUS detected lesions not seen on pre-operative scanning including 11 metastases (one suitable for resection), seven benign hepatic cysts and two were benign hepatic nodules. Forty-nine patients have remained free of disease and 25 have died with systemic disease (mean survival 10 months, range 2-24 months). In the seven patients diagnosed as having hepatic cysts at IOUS two have died of systemic disease. The remaining patients (n=12) who died with systemic disease had a negative IOUS. CONCLUSION: IOUS increases diagnostic yield but a significant proportion of patients with occult hepatic metastases are not detected. IOUS improves disease staging in some patients refining the indications for adjuvant therapy and enhancing the estimate of prognosis and improving decision-making.     

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。     

Micrometastatic colorectal cancer lesions in the liver

(Received for publication on Jan. 6, 1997; accepted on Sept. 2, 1997)     

Establishment of a syngeneic model of hepatic colorectal oligometastases

BACKGROUND: Regional and systemic therapies aimed at improving the outcome for patients with colorectal hepatic metastases have met with modest yet tangible success. Currently, liver resection remains the only curative treatment, but only a minority of patients are candidates for surgery. Animal models are an ideal way to study new treatments for patients with metastatic colorectal cancer. We propose a syngeneic animal model of hepatic colorectal metastases that simulates oligometastases, which is a clinical state considered amenable to regional therapeutic strategies. MATERIALS AND METHODS: BDIX (BD-9) rats underwent intrasplenic injection of DHD/K12/TRb (Prob/K12) cells to create hepatic metastases via the portal system. After injection of 5 x 10(6) cells, rats underwent laparotomy to determine metastatic burden. Histological analysis confirmed the presence of metastases from resected tumors. RESULTS: Fifty-three animals were prospectively treated and observed for the development of oligometastases defined as between 1 and 10 hepatic lesions. Thirty-six (68%) of the animals developed detectable metastases while 32 (60%) developed oligometastases (average = 4.40 +/- 2.67). Four animals had overwhelming metastatic liver and peritoneal disease. All animals underwent peritoneal examination and thoracotomy to ensure localized disease. Histological analysis of five hepatectomy specimens confirmed the presence of metastatic cancer. Animals with oligometastases were healthy as evidenced by normal feeding and grooming behavior. CONCLUSIONS: An animal model of oligometastatic colorectal cancer to the liver can reproducibly mimic the stage IV state in humans conducive to regional therapy and can be used reliably to test novel treatments and mechanisms of metastatic colorectal cancer.