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.     

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10

Prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombi (TT) in the trunk of the portal vein (PV) has been extremely poor. There have been few reports of long-term survivors with such an advanced condition. In this article, the case of a 62-year-old woman of HCC, who survived for 6 years and 9 months after an operation, with TT in the trunk of the PV is described. The patient not only had a primary tumor of 4 cm in diameter with TT but also multiple intrahepatic metastases in the bilateral lobe of the liver. A palliative lateral segmentectomy with tumor thrombectomy through the incised left first branch of the PV was performed. Moreover, an intraoperative ethanol injection for residual intrahepatic metastatic tumors was performed subsequently. Hepatic arterial infusion of anti-cancer drug with Lipiodol, intraportal continuous infusion of 5-FU and percutaneous ethanol injection therapy were performed suitably during the follow-up periods. The patient survived for 6 years and 9 months after operation and died of hepatic insufficiency with cancer. In this case a patient who suffered from HCC with TT in the trunk of the PV was successfully treated by multimodality procedures including hepatic resection with tumor thrombectomy.     

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.     

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.     

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.     

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.     

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.     

Evaluation of hepatic resection and hepatic arterial infusion chemotherapy for multiple liver metastases from colon cancer

We examined the significance of hepatic resection and hepatic infusion chemotherapy for multiple liver metastases from colon cancer. Twelve patients underwent curative hepatic resection for multiple liver metastases (more than five), and 10 of them received arterial infusion chemotherapy. The number of metastases ranged 5 to 30 (mean 9.4). Recurrence rates in the remnant liver were 50%, and five-year survival rates were 31%.     

Hepatic resections after chronotherapy: surgical aspects

Hepatic resection has always been recommended for the treatment of metastatic disease in selected patients. Surgeons have had modified their approach and timing of surgery since the introduction of chemotherapy. The authors report their experiences since the introduction of chronochemotherapy. From 1990 up to 1994, 9 hepatic resections were performed for metastatic colorectal carcinoma. During the same period, 11 arterial accesses were implanted for diffused hepatic disease. Of the 9 resected patients, 5 are still alive with a mean follow-up of 17.7 months with no signs of recurrent disease.     

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.     

Hepatocellular carcinoma: surgical treatment

Worldwide the hepatocellular carcinoma (HCC) is one of the most common malignancies. There is a coincidence with liver cirrhosis or chronic hepatitis B/C in most cases. HCC can be suspected by ultrasound and by rise of the tumor marker (AFP). Further investigations, like biopsies, are not necessary if angiography or computed tomography in combination with patient history and elevated AFP levels are positive. The prognosis of untreated HCC is extremely poor. Live expectancy of symptomatic patients is only a couple of weeks. Radical tumor removal by liver resection or transplantation is the only treatment with curative intent. However these options are only suitable for patients with limited disease. Five year survival after curative liver resection depends on the tumor stage, ranging from 25% to 67%. The results after liver transplantation are similar for small cancer. Large, symptomatic tumors are in most cases only suitable for palliative treatment (chemoembolisation, ethanol injection, chemotherapy, immunotherapy). The strong dependence of prognosis on tumor extent underlines the importance of screening patients with elevated risk of developing an HCC. The early recognition of small tumors allows curative therapy with good results.     

Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary gastric cancer

BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric cancer, it is usually presumed to be metastatic. However, this may not be true in a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This study was conducted to examine the clinicopathological factors of both conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a synchronous hepatectomy in combination with radical gastrectomy over the past 15 years was performed. RESULTS: Seven patients had metastatic gastric cancer, and seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node metastasis were the major features in the patients with metastatic gastric cancer. Early gastric cancer was found in three of the patients with the coexisting primary cancers. No patient with solitary metastatic cancer survived more than one year, but long-term survival of more than two years was achieved in two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the stomach and liver should be kept in mind in patients with gastric cancer concomitant with a solitary hepatic tumor, in order to provide optimal treatment.     

Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors

We performed the locoregional injection of OK-432/fibrinogen/thrombin to unresectable hepatic tumors metastasized from colorectal cancers, which were hardly controlled by arterial infusion chemotherapy. CEA was markedly decreased following this treatment, although abdominal CT did not show a significant reduction of tumor mass. This immuno-injection therapy may be a choice of treatment for metastatic liver tumors, refractory to treatment by conventional chemotherapy.     

Arteriovenous malformation mimicking recurrent medulloblastoma

Here we report on the case of a 51-year-old man who presented with a high-grade fever six weeks prior to hepatic resection. The resected specimen of the liver showed a well encapsulated and completely necrotic mass and some intrahepatic metastatic disease. Widespread multinodular recurrence in the liver remnant and metastatic foci in the bones were detected approximately one year after surgery. This case suggests that transcatheter arterial embolization--which aims to bring about necrosis of the tumor--followed by hepatic resection might increase the risk of early recurrence of hepatocellular carcinoma, due to the fact that tumor necrosis can facilitate the release of cancer cells from the primary tumor.     

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.     

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.     

Segmental liver resections, present and future-caudate lobe resection for liver tumors

BACKGROUND/AIMS: Resection of the caudate lobe of the liver is difficult to perform because of a deep location and an adjacency to the major vessels. METHODOLOGY: A total of 30 patients with hepatocellular carcinoma (HCC) originating in the caudate lobe underwent hepatic resection. The lobe was classified to Spiegel's portion, the process portion, and the caval portion. The operative procedure undertaken was chosen on the basis of tumor location as well as hepatic function of each patient. RESULTS: In 14 patients who had an HCC located at Spiegel's portion or the process portion, the tumor was removed by local resection of the caudate lobe (n = 10), or by resection combined with lobectomy (n = 2) or subsegmentectomy (n = 2). In 16 patients with an HCC at the caval portion, caudate lobe resections with preparatory lobectomy (n = 6), segmentectomy (n = 1), or subsegmentectomy (n = 4) were performed. In the other 5, isolated total or partial resection of the caudate lobe was carried out because of the presence of severe cirrhosis. All operations were defined as curative, but produced two operative deaths due to liver failure. The cumulative rate of overall survival was 41% at 5 years after surgery. CONCLUSIONS: Caudate lobe resection for HCC can be performed even in cirrhotic patients with a favorable surgical outcome.     

Treatment of colorectal cancer: hepatic metastasis

Almost one-third of patients dying from colorectal cancer have tumor limited to the liver. Systemic chemotherapy is the appropriate palliative management of patients with metastases to the liver and other sites. For many patients with isolated hepatic metastases, systemic chemotherapy is also the most appropriate treatment. However, results with systemic chemotherapy indicate that one-third or less of patients will respond to such treatments, and long-term survival is rare. In this report we provide information concerning the natural history of colorectal hepatic metastases, followed by the expected benefits with systemic chemotherapy. This information provides background for the regional therapeutic strategies of surgical resection, cryosurgery, and hepatic artery chemotherapy. We discuss the selection factors appropriate for such treatments, morbidity and mortality, and the potential long-term benefits of such approaches. The last section focuses on surgical considerations in hepatic resection and hepatic artery chemotherapy.     

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 intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially 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.