Comparison in survival between hepatic metastases of gastric and colorectal cancers

BACKGROUND/AIM: The outcome after hepatectomy and non-surgical treatment of liver metastases from gastric and colorectal malignancies are reported. METHODOLOGY: Between April 1988 and March 1994, 176 patients with metastatic liver cancer were treated at the First Department of Surgery, Kyoto Prefectural University of Medicine Hospital. RESULTS: All patients received multi-disciplinary treatment, and 51 underwent hepatectomy. The survival after hepatectomy for metastatic liver cancer from a colorectal primary was better than that for gastric cancer. The survival after hepatic arterial infusion (HAI) therapy for metastases from gastric cancer was better than that for colorectal cancer. CONCLUSION: Surgical resection may be the best treatment for liver metastases from colorectal cancer. HAI may be a better option for liver metastases from gastric cancer.     

Frequency of asymptomatic choroidal metastasis in patients with disseminated breast cancer: results of a prospective screening programme

AIM: To determine the frequency of visually asymptomatic choroidal metastasis in patients with disseminated breast cancer and its dependence on the incidence of metastasis by number and site of other organ metastases. METHODS: From January 1995 until April 1997 120 patients irradiated for disseminated breast cancer underwent ophthalmological screening for choroidal metastasis. No patient was symptomatic for ocular disease. 68 out of 120 patients were found to have metastases in one organ and 52 patients had metastases in more than one organ. 80% of the patients had bone metastases, 25% lung metastases, 22% liver metastases, 15% brain metastases, and 22% had metastases in other organs. RESULTS: Six patients (5%) were found to have asymptomatic choroidal metastases. Five patients had unilateral and one patient bilateral metastases. 52 patients with more than one involved organ had a significantly higher risk for asymptomatic choroidal metastasis (6/52, 11%) than 68 patients with metastases in only one organ (0/68) (p = 0.006). In univariate analysis a significantly higher risk was seen for patients with lung metastases (14% choroidal metastases versus 2% in patients without lung metastases, p = 0.03) and for patients with brain metastases (17% choroidal metastases versus 3% in those without brain metastases, p = 0.04). CONCLUSION: In disseminated breast cancer the incidence of asymptomatic choroidal metastases was 5% and increased to 11% when more than one organ was involved in metastatic spread. Risk factors for choroidal metastases were dissemination of disease in more than one organ and the presence of lung and brain metastases.     

Resection for multiple metastatic liver tumors after portal embolization

BACKGROUND: Five patients with bilateral multiple liver metastases (3 to 12 lesions) from colorectal cancer who underwent extensive liver resection after portal embolization are described. METHODS: Portal embolization of the right portal branch was performed 9 days to 8 months before hepatic resection. The location and number of metastases were determined by intraoperative ultrasonography at the time of liver resection to accomplish complete resection of the tumors. Extended right lobectomy was carried out in four patients, two of whom underwent additional wedge resection of nodules located in the left lateral segment. The other patient underwent right lobectomy associated with local resection of the tumor in the left lobe. RESULTS: The postoperative course in the five patients was uneventful, with no serious complication or liver dysfunction. Although one patient died of recurrence 28 months after liver resection, the remaining four patients were alive and free of cancer between 36 and 74 months after hepatectomy. CONCLUSIONS: The presence of bilateral multiple (four or more) metastatic liver lesions from colorectal cancer is not considered a contraindication for hepatic resection if thorough examination of the liver is performed with intraoperative ultrasonography and the surgical risk is minimal. Portal embolization appears effective for increasing the safety of hepatectomy for patients with small metastases who require major right-sided resection combined with wedge resection of the left lobe.     

Transcatheter arterial chemoembolization to hepatic metastases from colorectal cancer

Response of transcatheter arterial chemoembolization (TAE) and transcatheter arterial infusion chemotherapy to hepatic metastases was reported in 25 cases of colorectal cancer. The severity of liver metastases was H1 in 12 cases, H2 in 9 cases, and H3 in 4 cases. Liver metastases were found during surgery in 12 of these patients, and 13 showed metastases or recurrence in the liver after resections of primary lesions. Catheters were inserted selectively to the proper hepatic artery by Seldinger's method, followed by injection of embolizing agents (gelfoam particles of Lipiodol) with adriamycin or 5-FU + leucovorin in most cases. Response was assessed by blood CEA levels, diagnostic imaging, and period of survival. In 5 cases in whom liver resections were performed following TAE, response was assessed by histopathological findings of the resected specimens. Two patients showed partial response (PR), 12 no change (NC) and 11 progressive disease (PD) by diagnostic imaging. Blood CEA levels fell to less than 50% of pre-treatment levels in 26% of cases. Histological changes by TAE were confirmed in 4 of 5 cases after liver resections, but viable cancer cells were observed in all cases. A case of mucinous cancer showed no change histologically. As the other case of mucinous cancer showed PD by diagnostic imaging, TAE was not suggested to be suitable to treat cases of mucinous cancer. More improvements in the dosage, drugs and times of treatment were suggested to yield a better response rate in TAE therapy for liver metastases from colorectal cancer.     

A pilot study of cryochemotherapy for hepatic metastases from colorectal cancer

Cryosurgery of hepatic metastases from colorectal carcinoma is a form of local therapy for unresectable disease. After curative resection, failures occur in the liver, and at extrahepatic sites. This pilot study evaluated the toxicity and tolerance to cryotherapy and intraoperative chemotherapy for unresectable hepatic metastases from colorectal cancer. If after exploratory celiotomy for potential curative resection of hepatic metastases the patient was deemed unresectable because of location and/or number of lesions, cryosurgery and intraoperative chemotherapy with systemic 5-fluorouracil 600 mg/m2 and leucovorin 500 mg/m2 was performed. Four patients were treated with cryochemotherapy. All patients developed toxicity. Two patients developed grade II leukopenia on Postoperative Days 2 and 12, and grades II and III diarrhea on Postoperative Days 5 and 7, respectively. Grade III hyperbilirubinemia and thrombocytopenia occurred in one patient on Postoperative Days 3 and 7. Acute respiratory distress syndrome, postoperative ileus, and grade II mucositis occurred in one patient each. All patients had delays and dose reductions on their subsequent chemotherapy treatments secondary to toxicity. Two patients had disease progression, one had stable disease. and one is "disease free." Combining the tumoricidal effects of chemotherapy and cryosurgery is in theory a good concept. However, the toxicity of 5-FU and leucovorin is enhanced by this approach.     

A study of various complications in arterial infusion chemotherapy

Complications of arterial infusion chemotherapy were analyzed in 261 cases from December 1983 to December 1993 in our department. Their complications involved nausea and vomiting (40.6%), bone marrow suppression (33.3%), liver dysfunction (20.3%), gastric and duodenal ulcer (9.6%) and so on. Complications involving an implantable device were hepatic arterial obstruction (29.1%), reservoir obstruction (5.7%), dislocation of catheter (4.6%), infection of catheter (3.8%), and obstruction of catheter (1.9%). In another cases with hepatic arterial obstruction, we performed arterial infusion in another artery as a bypass or stopped the infusion. In cases with obstruction of catheter not able to be reopened, we reinserted the catheter. An obstructed and/or infected reservoir was removed or replaced. Nausea and vomiting were found in 46.3% of FAM arterial infusion method (FAM) cases, in 53.3% of 5-FU persistent arterial method (5-FU) + FAM cases, and in 40.5% of intermittently persistent arterial method (IP) cases. Gastric and duodenal ulcer were noted in 9.8% of FAM, 13.3% of 5-FU + FAM, and 8.1% of IP cases. There were no significantly statistical differences between the methods. Hepatic arterial obstruction predominantly occurred in 32.4% of IP and 26.7% of 5-FU + FAM and bone marrow suppression was predominant in cases in which ADM was used. The duration of obstruction after administration was 154.0 +/- 117.4 days on average (21-455 days). Complications of hepatic arterial infusion chemotherapy are based on various causes which can be managed for prevention. We intend to enhance safety and assure the greater effectiveness of hepatic arterial chemotherapy.     

Effect of ascorbic acid on hyperoxic rat astrocytes

The authors' clinical experience of treating almost exclusively inoperable liver malignancy in 149 patients by cryotherapy is reviewed. There was only one 30-day death; morbidity was modest. Postoperative carcinoembryonic antigen (CEA) changes were extremely predictive of outcome in patients with liver metastases from colorectal cancer. For the group in which CEA levels returned to the normal range, median survival exceeded 1000 days. In addition, the authors reported encouraging results with cryotherapy as an adjunct to resection.     

Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen)

OBJECTIVE: To determine the impact of adjuvant hepatic arterial infusion (HAI) on survival relative to resection alone in patients with radical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Nearly 40% to 50% of all patients with colorectal carcinoma develop liver metastases. Curative resection results in a 5-year survival rate of 25% to 30%. Intrahepatic recurrence occurs after a median of 9 to 12 months in up to 60% of patients. The authors hypothesized that adjuvant intraarterial infusion of 5-fluorouracil (5-FU) might decrease the rate of intrahepatic recurrence and improve survival in patients with radical resection of colorectal liver metastases. METHODS: Between April 5, 1991, and December 31, 1996, patients with colorectal liver metastases from 26 hospitals were stratified by the number of metastases and the site of the primary tumor and randomized to resection of the liver metastases followed by adjuvant HAI of 5-FU (1000 mg/m2 per day for 5 days as a continuous 24-hour infusion) plus folinic acid (200 mg/m2 per day for 5 days as a short infusion), or liver resection only. RESULTS: The first planned intention-to-treat interim analysis after inclusion of 226 patients and 91 events (deaths) showed a median survival of 34.5 months for patients with adjuvant therapy versus 40.8 months for control patients. The median time to progression was 14.2 months for the chemotherapy group versus 13.7 months for the control group. Grade 3 and 4 toxicities (World Health Organization), mainly stomatitis (57.6%) and nausea (55.4%), occurred in 25.6% of cycles and 62.9% of patients. CONCLUSION: According to this planned interim analysis, adjuvant HAI, when used in this dose and schedule in patients with resection of colorectal liver metastases, reduced the risk of death at best by 15%, but at worst the risk of death was doubled. Thus, the chance of detecting an expected 50% improvement in survival by the use of HAI was only 5%. Patient accrual was therefore terminated.     

Cancer: incidence and deaths in Canada, 1990

The results of superselective intra-arterial chemotherapy with Mitomycin C (SIAC) in cases of hepatic neoplasms continue to be poor. Survival time was related to the percentage of hepatic replacement (PHR) but only 19% of the patients with Stage I tumours (PHR < 25%) survived for over 5 years and all the others died within 4 years. The patients with hepatic metastases from colorectal cancer achieved a significantly better cumulative 5-year survival figure than those with hepatocellular cancer (P < 0.05). The median survival times for patients with hepatic metastases from colorectal cancer, hepatocellular cancer and gallbladder cancer were 15 months, 6 months and 13 months, respectively. The overall response rate was only 27% (26/97), that for primary liver cancer 20% (7/35), that for hepatic metastases from colorectal cancer 22% (8/37) and that for gallbladder cancer 44% (11/25) and the patients who responded to SIAC (n = 27) had a significantly better cumulative 5-year survival rate (P < 0.005). Cessation of SIAC was necessary in 74% (72/97) of the cases, because of tumour progression in 53% (51/97), major complications in 19% (18/97) and patient refusal in 3% (3/97). The results of this trial may be regarded as disappointing, and we are going to use SIAC for Stage I tumours only. Resection of the tumour continues to provide the only chance of a permanent cure with these patients.     

Determinants of survival following hepatic resection for metastatic colorectal cancer

Hepatic resection remains the only potentially curative treatment for metastatic colorectal cancer. This retrospective review study was undertaken in an attempt to identify factors that influence patient survival following hepatic resection for metastatic colorectal cancer. From January 1978 to December 1993, a total of 301 patients underwent a total of 345 planned hepatic resections for metastatic colorectal cancer. Of those, 245 patients had one resection, 44 had two resections, and 12 had three resections. For all patients the overall median survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was 17.2%. Average hospital stay was 9 days. Statistical analysis included univariate analysis using log rank comparisons, Kaplan-Meier survival curves, and multivariate analysis using Cox proportional hazards regression. The statistically significant factors that influenced survival were distribution of liver metastases, unilobar versus bilobar (p = 0.0001), resected versus nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins (p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival (p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.     

Hepatic cryosurgery for metastatic colorectal carcinoma

PURPOSE/OBJECTIVES: To review an innovative, potentially curative surgical approach for the treatment of select patients with colorectal cancer metastatic to the liver. DATA SOURCES: Published articles and reported and unreported research results. DATA SYNTHESIS: The liver is the primary site of recurrence in 60%-80% of patients who develop recurrent disease following resection of the colorectal primary cancer. Less than 25% of patients with liver metastases are candidates for hepatic resection because of the location or number of liver metastases. Hepatic cryosurgery provides a viable treatment option for some patients with unresectable metastatic colorectal carcinoma confined to the liver, including patients with bilobar and multiple lesions. CONCLUSIONS: Because colorectal cancer is the second most common cause of cancer mortality in the United States, interventions that improve survival rates are an important focus of care. With knowledge of patient selection criteria and implications of hepatic cryosurgery, informed oncology nurses are resources for patients contemplating this therapy. IMPLICATIONS FOR NURSING PRACTICE: Preoperative evaluation and postoperative nursing care focus on careful assessment, education, and interventions aimed at preventing and detecting complications unique to hepatic cryosurgery. Knowledge of hepatic cryosurgery as a treatment option for colorectal liver metastases, patient selection criteria, and related implications allows oncology nurses to serve as resources for patients and families considering this therapy.     

Arterial infusion chemotherapy of 5-FU and leucovorin for patients with liver metastases from colorectal cancer

Fifteen patients with liver metastases from colorectal cancer were treated by arterial infusion of 5-FU and leucovorin. Two regimens were performed. One was weekly bolus infusion of leucovorin following bolus infusion of 5-FU (bolus group), the other was 5 days continuous infusion of 5-FU and leucovorin in 3 weeks (continuous group). One PR was obtained both in the bolus group and in the continuous groups. The objective response rate was 11% in the bolus group and 20% in the continuous group. The one- and 2-year survival rates for these patients were 40% and 0% in the bolus group, and 80% and 60% in the continuous group, respectively. These results suggest that continuous arterial infusion of 5-FU and leucovorin was more effective than individual bolus arterial infusion of leucovorin and 5-FU for patients with liver metastases from colorectal cancer.     

CT of calcified liver metastases in colorectal carcinoma

PURPOSE: To assess the incidence, characteristics and prognostic significance of calcification within colorectal hepatic metastases. MATERIALS AND METHODS: A retrospective analysis of CT in 265 patients with locally advanced or metastatic cancer was performed. Four groups were defined: (a) calcification within liver metastases prior to therapy, (b) noncalcified liver metastases with development of calcification on therapy, (c) noncalcified liver metastases, and (d) advanced local tumour without liver metastases. The number of calcified deposits in each patient was documented. A marker lesion was analysed for character, distribution and percentage of calcification. Survival between the four groups was compared. RESULTS: Twenty-nine (11%) patients had calcified liver metastases at presentation and 10 (4%) developed calcification during chemotherapy. Analysis of a marker lesion showed that the most frequent characteristic was fine calcification with a variable distribution. The most frequent change on treatment was alteration in the extent of calcification. Calcification developing on treatment was usually central. There was no difference in survival between groups 1, 2 and 3, but groups 1, 2 and 3 had a shorter survival than group 4. CONCLUSION: Calcification of liver metastases shows a variable pattern and may develop or change during therapy. Liver metastatic calcification may not carry any prognostic significance in colorectal cancer.     

Intra-arterial liposomal adriamycin for metastatic adenocarcinoma of the liver

A liposome-entrapped liposome form of Adriamycin (Lip-ADM) has been demonstrated to cause less myocardial and gastrointestinal toxicity than free ADM. In the present study, Lip-ADM prepared by the remote loading method was administered to 3 patients with metastatic adenocarcinoma of the liver via a reservoir with the catheter located in the proper hepatic artery. The primary tumor was gastric cancer in 2 patients and sigmoid colon cancer in 1. Lip-ADM was administered at doses of 10, 20 or 50 mg per time. The total ADM dose was 170, 490, and 760 mg, respectively. No severe adverse effects, such as nausea, vomiting, stomatitis, alopecia or cardiotoxicity, were observed in any of the patients. Although mild leukocytopenia (2,800/microliters) was observed in 1 patient, anemia or thrombocytopenia did not occur. The survival time was respectively 6, 15, and 17 months from the start of Lip-ADM administration. A partial response was obtained in 1 patient and stable disease in 1 patient. Administration of Lip-ADM via a reservoir appears to be a useful treatment for patients with metastatic adenocarcinoma of the liver, since the low toxicity of this preparation allows an increase of the total dose of ADM.     

The approach to the patient with single and multiple liver metastases, pulmonary metastases, and intra-abdominal metastases from colorectal carcinoma

Recurrent colorectal carcinoma constitutes a major health care problem, with 90,000 patients diagnosed annually with metastatic disease. Recent advances have offered treatment to selected patients with liver, lung, and intra-abdominal metastases. Resection of liver secondary tumors improves 5-year survival from 0% to approximately 30% and offers the only possibility for cure. As experience mounts, hepatic surgery can be performed with quite acceptable morbidity and mortality. Adjuvant therapies are being developed that may improve results with surgery alone. Cryoablation is a new technique that appears to effectively eradicate liver tumors, but its role remains to be defined. In patients with unresectable disease, the benefit of hepatic artery infusion of chemotherapy is unproven. Resection of pulmonary metastases significantly improves survival in patients with solitary nodules. Consistent data regarding the benefit of pulmonary metastatectomy in patients with multiple nodules are not available. Combined cytoreductive surgery and intraperitoneal hyperthermic chemotherapy is being investigated as a treatment for peritoneal carcinomatosis from colorectal cancer. Although selected patients may benefit, this combined treatment modality appears to be less effective in patients with colorectal cancer than with other types of cancer.     

Long-term evaluation with DMSA-Tc 99m scintigraphy of renal parenchymal involvement in children after shockwave extracorporeal lithotripsy

BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.     

Indication of prophylactic hepatic arterial-infusion chemotherapy after hepatic resection for liver metastases from colorectal cancer

The purpose of this study was to clarify the indication of prophylactic hepatic arterial-infusion chemotherapy (PHAIC) after hepatic resection for liver metastases from colorectal cancer. Sixty-one patients underwent curative hepatectomy, and 27 of them were treated with PHAIC using implantable port. According to clinicopathological factors of primary colorectal cancer and liver metastases, the prognoses were analyzed. In conclusion, PHAIC was not useful for patients who had distant lymph node metastases (paraaortic lymph node) from primary cancer.     

Management strategies for colorectal liver metastases--Part II

Liver metastases are relatively common in colorectal cancer and a small proportion of patients may benefit from resection of these liver metastases. In a selected subgroup of patients, 5-year survival rates of 25-35% may be achieved following liver resection. These survival figures compare favourably with those of patients with untreated liver secondaries. In the second part of this review the surgical and non-surgical treatment options for treating colorectal liver metastases are examined in detail.     

Efficacy of combination therapy (hepatectomy and prophylactic arterial chemoinfusion) for liver metastases of colorectal cancer

From 1979 to 1997, 146 patients had hepatectomy for metastases of colorectal cancer (curative B: 122; curative C: 24). We categorized the severity of liver metastases as follows, H1: one lobe; H2: bilateral but less than five, and H3: bilateral with five or more lesions. In H1 and H2 patients, we compared the survival rate after resection alone (including repeat hepatectomy) with that after combination therapy (resection and prophylactic arterial chemoinfusion of 12-24 g of 5-FU). In H1 patients, the 3-year survival rate of the resected group (n = 74) and combination group (n = 6) was 47.2 and 53.3, respectively. In H2 patients, the resected group (n = 16) and combination group (n = 7) had survival rates of 34.5 and 100%, respectively. In H1 cases, the 3-year recurrence rate in the remnant liver was 63.4 versus 16.7% and in H2 cases it was 58.0 versus 0%. H3 patients received one week of continuous prophylactic arterial chemoinfusion [total dose of 5-FU = 6 g]. All four patients in the H3 combination group are alive at 20, 13, 13, and 12 months after resection, while the median survival of the resection only group (n = 4) was 12.5 months. We suggest that our combination therapy may be applicable to all patients with liver metastases of colorectal cancer.     

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H1, H2, and H3 was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H1 and patients with H3. Median survival of patients with n0, n1, and n2 was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n0 and patients with n2. Median survival of 6 patients with H1 and n0 and of 17 patients with H3 and n2 was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.