Consistent hepatic metastasis of human colorectal cancer in severe combined immunodeficient mice

A major stumbling block in the study of human colorectal cancer metastasis has been the lack of an effective in vivo model producing liver metastasis on a consistent basis. In this study surgical specimens of colorectal carcinoma were implanted in scid mice and studied for engraftment, growth, and the capacity to produce hepatic metastases. Human colorectal cancers would engraft and propagate in the subcutis and intraperitoneally. Sporadic metastasis to the liver occurred in 3 of 54 (6%) animals with cancer implanted subcutaneously. Liver metastasis occurred in 24 of 25 (96%) mice with cancer implanted in the gonad fat pad. Tumor growth to extremely large volumes subcutaneously did not enhance metastatic potential, and neither did longer term growth in the subcutaneous space. Tumor placed in the gonad fat required no special manipulation and in most cases a single piece of solid tumor was implanted. In situ hybridization confirmed the persistence of the human tissue in these metastasizing tumors. Our model will allow for the study of the processes involved in metastasis of solid tumors, characterization of differences between the primary tumor and the metastatic one, and evaluation of possible therapeutic modalities.     

Intra-arterial preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer

We treated 18 cases with intra-hepatic arterial infusion chemotherapy after resection of hepatic metastasis from colorectal cancer (June 1991-September 1997). Eight cases were H1, 7 were H2, and 3 were H3. Hepatic lobectomy was done in 3 cases, lobectomy + partial resection in 2 cases, and partial resection in 13 cases. All cases received high-dose intermittent 5-FU infusion (WHF = 5-FU 1,000 mg/m2/5 hrs/w) on an outpatient basis. The total frequency of WHF was 4-54 times (average 29), and total 5-FU doses ranged from 6.0 to 81.0 g (average 40 g). The 1- and 5-year cumulative survival rates were 100% and 77.5% in all patients 100% and 87.5% in H1 group and 100% and 64.3% in H2 + H3 group, respectively. There was no significant difference of survival between the H1 and H1 + H3 groups. The 1- and 5-year recurrence rates in residual liver were 5.9% and 14.4%, respectively. One of 2 cases with residual liver recurrence was resected for metastasis again, and the patient is now in a disease-free state. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect for their survival, not only in H1 group but also in H2 + H3 group.     

Adjuvant intra-arterial chemotherapy with gastrin receptor antagonist after hepatic resection in colorectal cancer metastasis

The aim of this study was to determine whether chemo-endocrine therapy after the resection of liver metastasis from colorectal cancer would prevent recurrence in the remnant liver and prolong survival. Eleven colorectal cancer patients underwent hepatic resection for liver metastasis. Subsequently, they were administered Proglumide gastrin antagonist 1,200 mg/day + 5'-DFUR 800 mg/day for 2 years. In seven of them, MMC 6-10 mg and ADM 20 mg were infused intra-arterially every two weeks alternately for one year. In four of them, 5-FU 250 mg/day was infused for seven days continuously intra-arterially every two weeks for one year. Recurrence in the remnant liver occurred in four of 11 patients. All of these patients underwent repeated hepatectomy. The mean disease-free survival in the remnant liver was 37 months and the five-year survival rate was 91%. These results indicate that intra-arterial chemotherapy with gastrin receptor antagonist might be effective for adjuvant therapy in patients with resectable liver metastasis from colorectal cancer.     

Treatment of hepatic metastases of colorectal cancer by electrochemotherapy: an experimental study in the rat

A patient with a tear of the thumb ulnar collateral ligament and simultaneous extensor pollicis brevis and extensor pollicis longus disruptions is reported. No report of a similar constellation of injuries was found in the literature.     

Prognosis of hepatic metastasis from colorectal cancer following hepatic resection and arterial infusion chemotherapy--assessment from the percentage of tumor involved area

Prognosis of hepatic metastasis from colorectal cancer following hepatic resection and arterial infusion chemotherapy was studied from the percentage of tumor involved area (PTIA). The PTIA was calculated by the following formula: sigma S'/sigma S, with S' as the tumor area and S as the liver area on each CT slice. The subjects were 25 cases of hepatic resection (HR), and 31 cases of hepatic arterial infusion chemotherapy (HAI). The PTIA of the cases of HR and that of HAI was 1.5 to 25.9% and 0.8 to 31.3%, respectively. For comparison, all cases were divided into group A, which was not more than 10% of the PTIA, and group B, which was more than 10% of the PTIA. In the cases of HR, the prognosis of group A was significantly better than that of group B (p < 0.05). In the cases of HAI, the prognosis of group A was better than that of group B. Even in group A, the prognosis of the cases of HR was significantly better than that of HAI (p < 0.05). These results suggest that the PTIA in the cases of HR and HAI for metastasis from colorectal cancer is important factor which reflects the prognosis.     

Resection of hepatic metastases from colorectal cancer

BACKGROUND/AIMS: Long term results of hepatic resection for metastases from colorectal cancer depend upon several factors which are related to both features of primary cancer and of metastases. The aim of this study was to evaluate prognostic factors that best correlate with long-term results. MATERIALS AND METHODS: Fifty-eight hepatic resections were performed for colorectal cancer metastases. Long-term results were evaluated in relation to age of patients, features of primary tumor, features of metastases, section margin, number of intra-operative blood transfusions and execution of adjuvant chemotherapy. RESULTS: Overall 5-year survival rate was 17%. 5-year survival rate in patients with stage B primary tumor was 63%, in patients with late metachronous metastases it was 28%, in patients with section margin > 1 cm it was 33% and in patients who did not receive intra-operative transfusions it was 45%. Patients with a solitary metastasis or with metastases sized less than 4 cm and those who received adjuvant chemotherapy also showed a better survival than the others. CONCLUSIONS: Better results were observed in patients without nodal involvement of the primary tumor. Patients with a small solitary metachronous metastasis that appeared more than one year after the colorectal resection and resected with a section margin of more than 1 cm, also showed good results.     

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 24 h and 48 h after the addition of 1.0 microgram/ml and 10.0 micrograms/ml PGD2. The growth of SW480 cells was inhibited 48 h, but not 24 h, after the addition of 1.0 microgram/ml, and 24 h and 48 h after the addition of 10.0 micrograms/ml, while that of LS174T was inhibited by both doses after 24 h and 48 h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24 h after the addition of 10.0 micrograms/ml PGD2. The cell cycle of LS174T cells was arrested at the G0 + G1 phase 24 h after the addition of 1.0 microgram/ml and 10.0 micrograms/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.     

Bone metastasis from colorectal cancer in autopsy cases

The incidence of bone metastasis from colorectal cancer is reported to be 10.7% in autopsy cases. However, the characteristics of the primary cancers, as well as the patterns of bone metastasis, remain unclear. We analyzed the clinical and autopsy records of 118 patients with primary colorectal cancer treated either surgically or conservatively and eventually autopsied between 1970 and 1987 at Toranomon Hospital in Tokyo. Bone metastasis was detected in 23.7% (28/118). The average age of patients with bone metastasis was lower than that in patients without bone metastasis (P < 0.02). Cancers to the rectum and cecum were accompanied by bone metastasis more frequently than cancers of other portions of the colon. Signet-ring cell carcinoma showed a high incidence of bone metastasis (P = 0.041). Bone metastasis from colorectal cancer was associated with liver or lung metastases (P < 0.0001). These results indicated that bone metastasis from colorectal cancer is not as infrequent as previously described.     

The preventive effect of weekly high-dose 5-FU infusion (WHF) after resection of hepatic metastasis from colorectal cancer

Hepatic metastasis is often found even after resection of hepatic metastases from colorectal cancer. This implies that the micrometastasis already existed in residual liver when the resection was performed, and so complete recovery with resection alone is rare. We have been using a weekly high-dose 5-FU HAI (WHF = 5-FU 1,000 mg/m2/5 hrs/qw) since 1991, which has preventive effects for metastasis in residual liver as compared to a group treated without infusion chemotherapy. Hepatectomy was performed in 30 of 113 cases of hepatic metastasis from colorectal cancer during the past 16 years. For comparison, we divided the 30 cases into group A1 (16 cases H1:12, H2:4), which received hepatectomy only, and group A2 (14 cases H1:8, H2:4, H3:2), which additionally received infusion chemotherapy. The 1- and 3-year (cumulative) survival rates were 64.6% and 32.3% in group A1, and 100% and 75.3% in group A2 respectively in which the treatment outcome was significantly higher. The 1- and 3-year recurrence rates were 41.7 and 66.3 in group A1, and 8.3% each in group A2, respectively, which reveals that metastasis in residual liver was controlled in group A2. Other metastases were seen in lung (6 cases), bone (2 cases), hepatic hilar lymph node (3 cases), brain (1 case) and local (3 cases) in group A1, while only one metastasis in each brain and locally was seen in group A2 so far. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect not only for the recurrence in residual liver but also for other metastases. Therefore, as improvement in the survival rate is expected.     

Treatment of colorectal cancer with monoclonal antibodies

This article reviews the treatment of colorectal carcinoma with monoclonal antibodies. Since the late seventies, several hundred patients with advanced disease have been treated with unconjugated antibodies, especially Mab 17-1A. The response rate of the studies has been less than 10%. In contrast, Mab given as adjuvant treatment for Duke's C colorectal carcinoma increased the five year survival with 30%. The actions of different types of immunoconjugates are reviewed.     

Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.     

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.     

Treatment of colorectal cancer. Pharmaco-economic aspects

By using caring behaviors and recognizing the grief process, the nurse can help the dying patient and family gain emotional control, complete unfinished business, work through anticipatory grief, and learn how to let go.     

Liver metastasis rare in colorectal cancer patients with fatty liver

BACKGROUND/AIMS: As no reports in terms of the relationship between fatty liver and liver metastasis of colorectal cancer clinicopathological analysis of colorectal cancer patients with fatty were found a liver was carried out. PATIENTS AND METHODS: Among 839 patients with single colorectal carcinoma who underwent operations at our department between 1985 and 1994, 121 patients were designated as fatty liver using ultrasonography (FL group). The remaining 718 non-fatty liver patients with colorectal cancer (NFL group) were compared to the FL group regarding clinicopathological aspects. RESULTS: (1) There were only two patients who had liver metastasis in the FL group (1.7%), while the NFL group included 115 patients with liver metastasis (16.0%) (p < 0.01). (2) The five-year survival rate of the FL group was 95.7%, which was significantly higher than that in the NFL group (9.8%) (p < 0.001). (3) In the multivariate analysis, the fatty liver was identified as an independent prognostic factor. CONCLUSIONS: The FL group had a much better prognosis compared to the NFL group. Especially, liver metastasis was extremely rare in the FL group. We believe that these results will lead to the clarification of the liver metastasis mechanism.     

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.     

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.     

Surgical treatment of pulmonary metastasis of colorectal cancer. Prognostic survival factors

SURVIVAL RATES: Less than 5% of patients with pulmonary metastasis from colorectal carcinoma will survive at 5 years, but 30% will survive at 5 years after surgical treatment. MAIN PROGNOSTIC FACTORS: The number of nodules, presence of regional lymph node metastases, disease-free interval between treatment of the primary tumor and development of metastasis as well as serum CEA level are the main prognostic discriminants. INDICATIONS FOR SURGERY: An aggressive operative approach is indicated even when there are pulmonary and extra-pulmonary localizations. Repeat thoracotomy is warranted for recurrent disease.     

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.     

Implication of VEGF and MMPs in hepatic metastasis of human colon cancer

In contrast to other types of cervical adenocarcinoma, well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix is unique for its tendency to develop in young women and its excellent prognosis. Until now, no tumor recurrence has been reported in the English literature following surgical treatment that varies from conization to radical hysterectomy. We report a case of 47-year-old female who presented with postcoital bleeding and was treated by radical hysterectomy for FIGO (International Federation of Gynecologists and Obstetricians) Stage Ib cervical carcinoma, in which the preoperative cervical biopsy diagnosis was adenocarcinoma. The patient was well at follow-up nine months after surgery. A literature review including treatment implications is presented.     

Metachronous liver metastasis of colorectal cancer: timing of occurrence and efficacy of adjuvant portal chemotherapy

We estimated the time of occurrence of metachronous liver metastasis in colorectal cancer patients from tumor diameter and doubling time. Micro-metastasis was present prior to operation in most patients and a few metastatic cases could have been initiated by the surgical procedure. Portal chemotherapy is more effective against liver metastasis than intravenous infusion because a higher drug concentration in the liver can be obtained. This efficacy of portal chemotherapy on survival was also observed in a rat model. Thus perioperative adjuvant treatment should be undertaken for metastasis which already existed before the operation and adjuvant chemotherapy via portal vein is the treatment of choice. The no touch isolation technique is also needed to avoid spreading of tumor cells during surgery.