Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection.

BACKGROUND: Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND. METHODS: Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively. RESULTS: There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87). CONCLUSIONS: We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.

Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity.

BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Development of an outcomes management program at an academic medical center.

BACKGROUND: With the advent of managed care, academic medical centers have been challenged to lower costs and to document their claims of high quality outcomes. A successful method to achieve these objectives must not interfere with the academic missions of research and teaching. At M. D. Anderson Cancer Center, we initiated a program that would reduce practice variability and increase quality with a model that was familiar to the faculty. METHODS: Professional staff members were divided into disease site groups that included physicians, nurses, and other allied health staff. Each group developed practice guidelines and Collaborative Care Paths, based on evidence in the publications and on expert opinion. Desired outcomes were prospectively defined during this process. Before implementation, paths and guidelines underwent peer review. RESULTS: The faculty actively participated in the development and implementation of the program that was viewed as a means of empowerment to deal with managed care. Nearly 1000 patients have been entered on the B8 paths that have been implemented to date. CONCLUSION: A physician-driven outcomes management program permits delivery of high quality care and supports outcomes research while decreasing cost in an academic setting.

Improved survival after resection of colorectal liver metastases.

BACKGROUND: The goal of this study was to determine if staging with intraoperative ultrasound (IOUS), assessment of porta hepatis lymph nodes, and evaluation of resection margins can improve selection of patients likely to benefit from resection of colorectal liver metastases. METHODS: A retrospective evaluation was performed on patients undergoing celiotomy with intent to resect colorectal liver metastases. Patients were considered unresectable if extrahepatic disease was identified by peritoneal exploration or if IOUS demonstrated greater than four lesions or the inability to achieve negative margins. Tumor-negative margins were confirmed by pathologic evaluation. Actuarial 5-year survival was calculated using the method of Kaplan and Meier. RESULTS: Median follow-up is 25 months. Of the 151 patients undergoing operative exploration, 107 (71.0%) underwent liver resection (all margins tumor negative). Three operative deaths occurred in this group (2.8%). The disease of 30 patients (19.8%) was considered unresectable due to extrahepatic involvement, and that of 14 patients (9.2%) was demonstrated by IOUS to be unresectable. Five-year actuarial survival was 44% for the resected group and 0% for the unresectable patients (p < 0.0001). CONCLUSIONS: IOUS, portal node assessment, and pathologic margin evaluation improves the selection of patients likely to benefit from resection of colorectal liver metastases.

Hepatic artery chemoembolization or embolization for primary and metastatic liver tumors: post-treatment management and complications.

This paper describes complications and patient management issues associated with hepatic arterial chemoembolization (HACE) and embolization (HAE) used to treat liver malignancies and characterizes patient survival based on histologic tumor type. We performed a retrospective review of all patients treated with HACE or HAE between January 1, 1988 and December 31, 1990. During the study period, 314 HACEs and HAEs were performed in 121 patients. Ninety-six of the patients (79%) were treated for neoplasms metastatic to the liver. The morbidity rate following HACE and HAE in this study was 5.1%. The major complications included portal vein thrombosis, hepatic abscess, and liver failure. The treatment-related mortality rate was 4.1%. Fever and ileus were the most common management problems following HACE or HAE. Median survival for patients with liver metastases varied according to histologic type, and median survival for patients with hepatocellular cancer was 306 days. Morbidity and mortality from HACE and HAE to treat liver tumors can be minimized by proper selection and careful management of patients. HACE or HAE alone was not curative in any of these 121 patients. An understanding of treatment-related side effects is necessary to aid in the management of patients following HACE or HAE.

Complications and failures of subclavian-vein catheterization.

BACKGROUND: Although catheterization of the subclavian vein is a common procedure, the risk factors for complications and failures, with the exception of the physician's experience, are poorly understood. Ultrasonography has been recommended to help guide the placement of central venous catheters. METHODS: We conducted a prospective randomized trial of ultrasound-guided location of the subclavian vein as compared with standard insertion procedures. In the group of patients undergoing catheterization with ultrasound guidance, the site of the insertion was marked before the catheterization attempt; real-time ultrasound guidance was not used. The 821 eligible patients (411 in the ultrasound group and 410 in the control group) underwent catheterization in a single procedure suite under controlled nonemergency conditions, in most cases for the administration of chemotherapy. RESULTS: Ultrasound guidance had no effect on the rate of complications or failures of subclavian-vein catheterization (risk ratio for complications, 1.00; 95 percent confidence interval, 0.66 to 1.52; risk ratio for failures, 1.04; 95 percent confidence interval, 0.72 to 1.50). In multivariate analyses, prior major surgery in the region (P = 0.002), a body-mass index (the weight in kilograms divided by the square of the height in meters) higher than 30 or lower than 20 (P = 0.009), and previous catheterization (P = 0.043) were associated with failed attempts. Complications were also associated with failed attempts: 52 of the 721 patients (7.2 percent) in whom catheterization was successful had complications, as compared with 28 of the 100 patients (28 percent) in whom physicians were unable to place catheters. The number of needle passes was strongly associated with the rates of failure and complications. The complication rate rose from 4.3 percent with one pass to 24.0 percent with more than two passes. CONCLUSIONS: Ultrasound guidance of subclavian-vein catheterization, as used in this study, was not beneficial. In patients at highest risk for complications and failures, catheterization should be attempted by the most experienced physicians available.

Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion.

OBJECTIVE: In many hospitals, the only sterile precautions used during the insertion of a nontunneled central venous catheter are sterile gloves and small sterile drapes. We investigated whether the use of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, and large drape) would lower the risk of acquiring catheter-related infections. DESIGN: Prospective randomized trial. SETTING: A 500-bed cancer referral center. METHODS: We randomized patients to have their nontunneled central catheter inserted under maximal sterile barrier precautions or control precautions (sterile gloves and small drape only). All patients were followed for 3 months postinsertion or until the catheter was removed, whichever came first. Catheter-related infections were diagnosed by quantitative catheter cultures and/or simultaneous quantitative blood cultures. RESULTS: The 176 patients whose catheters were inserted by using maximal sterile barrier precautions were comparable to the 167 control patients in underlying disease, degree of immuno-suppression, therapeutic interventions, and catheter risk factors for infections (duration and site of catheterization, number of catheter lumen, catheter insertion difficulty, reason for catheter removal). There were a total of four catheter infections in the test group and 12 in the control group (P = 0.03, chi-square test). The catheter-related septicemia rate was 6.3 times higher in the control group (P = 0.06, Fisher's exact test). Most (67%) of the catheter infections in the control group occurred during the first 2 months after insertion, whereas 25% of the catheter infections in the maximal sterile precautions group occurred during the same period (P < 0.01, Fisher's exact test). Cost-benefit analysis showed the use of such precautions to be highly cost-effective. CONCLUSION: Maximal sterile barrier precautions during the insertion of nontunneled catheters reduce the risk of catheter infection. This practice is cost-effective and is consistent with the practice of universal precautions during an invasive procedure.

Comparative tumor localization of whole immunoglobulin G anticarcinoembryonic antigen monoclonal antibodies IMMU-4 and IMMU-4 F(ab')2 in colorectal cancer patients.

BACKGROUND: Previous studies in the literature have suggested that radiolabeled F(ab')2 fragments might be superior to whole immunoglobulin G (IgG) for imaging and therapy of cancer because of their greater penetration in tumors. To test this hypothesis, the authors compared tumor and normal tissue uptake along with plasma clearance of 125I-labeled monoclonal antibody (MoAb) IMMU-4 whole IgG with its 131I-labeled F(ab')2 fragment. METHODS: Five patients with either liver metastases from colorectal cancer (n = 4) or intact primary tumors (n = 1) received a combination of 125I-IMMU-4 IgG (2 mCi/1 mg) plus 131I-IMMU-4 F(ab')2 (10 mCi/1 mg) as a single 1-hour intravenous infusion on day 1. Serial blood samples were taken for up to 72 hours postinfusion to determine plasma clearance of each MoAb. On days 3-9, patients underwent exploratory laparotomy in which biopsies of tumor as well as normal tissues (liver, normal colon, lymph node, and blood) were obtained. Tissues were weighed and counted in a gamma counter, and the percent of injected dose per kilogram (%ID/kg) of each antibody, along with the radiolocalization index (RI), was computed (RI = %ID/kg tumor.%ID/kg normal tissue). RESULTS: Tumor uptake of both antibodies (2.3 +/- 0.53 %ID/kg) was significantly higher than that of normal tissues (0.56 +/- 0.12; P < 0.001), except for blood (2.8 +/- 0.83), resulting in an RI > or = 3. There were no significant differences in uptake (%ID/g) between F(ab')2 and IgG (F[ab']2 = 2.0 +/- 0.57; IgG = 2.6 +/- 0.94). The mean +/- SD of plasma T1/2 was slightly shorter for F(ab')2 (28.8 +/- 7.2 hours) than for IgG (45.9 +/- 16.7; P = 0.08). CONCLUSION: In short, the biodistribution and pharmacokinetics of IMMU-4 F(ab')2 were comparable to those of IMMU-4-IgG.

Adjuvant hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases.

We performed a prospective study of adjuvant hepatic arterial infusion chemotherapy after resection of colorectal liver metastases. We placed hepatic arterial infusion ports in 20 consecutive patients undergoing curative resection of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5-fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months. Nine of the 18 evaluable patients (50%) have developed recurrent colorectal cancer. The liver was the only site of failure in 3 of 18 patients (17%), and extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without recurrence are alive. The median survival of the patients without recurrent disease is 39 months, compared with 27 months for those with recurrent metastatic disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion chemotherapy compared with historical controls treated with surgery alone, we have observed a decreased incidence of recurrent disease after liver resection for metastases. We recommend that patients who undergo hepatic resection for colorectal metastases be considered for postoperative adjuvant chemotherapy to decrease the likelihood of recurrence and to improve survival.

Technical considerations and complications associated with the placement of 180 implantable hepatic arterial infusion devices.

BACKGROUND: Treatment regimens with hepatic arterial chemotherapy infusion are being investigated in an attempt to improve survival and quality of life for patients with primary and metastatic liver malignancies. The successful delivery of chemotherapeutic drugs through an implantable hepatic arterial infusion device depends on the surgeon's understanding of hepatic arterial anatomy, the proper cannulation technique, and the operative measures necessary to prevent misperfusion of drug. METHODS: Between January 1, 1987, and December 31, 1991, we placed implantable hepatic arterial infusion devices in 180 patients. The records of these patients were review to determine (1) the incidence and surgical management of variant hepatic arterial anatomy and (2) the complications associated with surgical placement of these devices. RESULTS: Variant hepatic arterial anatomy requiring ligation of the variant vessel or nonstandard cannulation was seen in 66 patients (36.7%). Treatment response rates and duration of treatment were no different for these 66 patients than for the 114 patients with standard hepatic arterial anatomy (p = 0.94). There were no operative deaths in this series. Operative or early postoperative (within 30 days) complications occurred in 10 patients (5.5%). However, late complications or device-related malfunctions developed in 52 patients (28.8%). CONCLUSIONS: An understanding of regional arterial anatomy is required to surgically place a catheter to achieve bilobar hepatic arterial perfusion and avoid gastroduodenal misperfusion of drug. Placement of hepatic arterial infusion devices has a low rate of early morbidity, but surgeons should be aware of late complications that may develop in patients undergoing hepatic arterial chemotherapy infusion through an implantable device.

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration.

BACKGROUND: Hepatic arterial infusion of doxorubicin has produced tumor response in hepatic malignancies; however, the limited success of these treatments is related in part to dose-limiting systemic toxicities. The purpose of this study was to determine whether a novel venous isolation-chemofiltration system could limit systemic exposure to doxorubicin after hepatic arterial infusion. METHODS: Doxorubicin (1 or 3 mg/kg) was infused in the hepatic arteries of domestic pigs after complete hepatic venous isolation was achieved with a dual-balloon vena cava catheter. The hepatic vein effluent was pumped through an extracorporeal carbon chemofiltration circuit. Doxorubicin levels were measured in prefilter (hepatic vein), postfilter, and systemic serum at intervals up to 1 hour after drug infusion. RESULTS: Complete hepatic venous isolation with extracorporeal chemofiltration significantly reduced (> 90%) the postfilter and systemic levels of doxorubicin compared with prefilter levels (p < 0.01). At the time animals were killed 7 days after infusion of doxorubicin (3 mg/kg), tissue levels of doxorubicin in the liver showed a 16-fold increase compared with levels in the heart (p < 0.01). CONCLUSIONS: For chemotherapeutic drugs like doxorubicin with a low first-pass extraction by the liver, the novel system described herein achieved significant reduction in systemic drug exposure. This system will allow dose intensification of doxorubicin administered by hepatic arterial infusion to treat hepatic malignancies.

Monoclonal antibody imaging in patients with colorectal cancer and increasing levels of serum carcinoembryonic antigen. Experience with ZCE-025 and IMMU-4 monoclonal antibodies and proposed directions for clinical trials.

In an effort to identify the site of recurrent colorectal cancer in patients with occult metastasis and increasing serum CEA levels, we conducted two trials using monoclonal antibodies (MoAb) against CEA. The first utilized Indium-111-labeled ZCE-025; an immunoglobulin G1 (IgG1) anticarcinoembryonic antigen (anti-CEA) antibody (Hybritech, San Diego, CA). The second study used Tc-99m-labeled Fab' fragment of IMMU-4 (Immunomedics, Morris Plains, NJ). Eighteen patients were imaged with the ZCE-025 and 14 with the Tc-99m Fab' IMMU-4. True-positive scans, defined as at least one correct correlation of the MoAb scan and surgical/histologic findings, were observed in 12 of 15 patients undergoing exploration or biopsy using the ZCE-025 and 11 of 14 using the IMMU-4. There were no true-negative scans with the ZCE-025 and only 2 of 14 with the IMMU-4. There were 3 false-positive scans with the ZCE-025 and 1 of 14 with IMMU-4. There were no false-negative scans with either ZCE-025 or IMMU-4. Four (31%) of 13 patients undergoing exploration and imaged with ZCE-025 and 5 (36%) of 14 imaged with IMMU-4 had complete tumor resection. Treatment decisions were affected in 3 (16%) of 18 ZCE-025-imaged patients and 3 (21%) of 14 IMMU-4 ones. Two (14%) of 14 patients imaged with IMMU-4 had negative MoAb scans and negative laparotomies. Despite these findings, it is not known whether such early detection and resection will translate into improved survival rates. The authors suggest two randomized studies, one designed to ascertain the role of MoAb added to blind exploratory laparotomy. In that study, patients with increasing CEA levels and a negative workup will be randomized to an exploratory laparotomy preceded by MoAb anti-CEA scans or a straight exploratory laparotomy without the assistance of a MoAb anti-CEA scan. Endpoints will be differences in complete resectability and survival. A second study will examine the merits of blind exploratory laparotomies. In that study, patients with increasing CEA levels and a negative workup would be randomized to MoAb imaging, exploratory laparotomy, and radioimmunoguided surgery, and the other cohort of patients would continue to have conventional radiologic workup. Exploration in this latter group would be performed only when indicated by radiologic or endoscopic studies. The endpoint of the study would compare survival in the two cohorts of patients. These two studies may ultimately settle the debate regarding the correct approach to patients with occult metastatic colorectal cancer and a increasing levels of serum CEA.

Increased doxorubicin levels in hepatic tumors with reduced systemic drug exposure achieved with complete hepatic venous isolation and extracorporeal chemofiltration.

We evaluated a novel system of complete hepatic venous isolation and chemofiltration (CHVI-CF) to reduce systemic drug exposure following regional hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 tumors were given doxorubicin via either hepatic arterial infusion (HAI) or portal venous infusion (PVI). A dual-balloon vena cava catheter and extracorporeal chemofilter were used to capture and filter hepatic venous blood in experimental animals. Control animals received chemotherapy without hepatic venous isolation and chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and experimental animals had similar doxorubicin levels in their livers and VX-2 tumors, but experimental animals showed a significant reduction in doxorubicin levels in systemic plasma, heart, and kidney tissue as compared with control animals (P < 0.01). HAI produced a 4-fold increase in doxorubicin levels in VX-2 tumors as compared with the drug levels obtained using PVI (P < 0.01). A single HAI of 3 mg/kg doxorubicin in animals treated with CHVI-CF produced marked tumor necrosis at 7 and 14 days after treatment. By increasing the total body clearance of doxorubicin, this system will allow HAI of higher doses of drug in attempts to improve the antitumor response.

Endoscopic laser recanalization is effective for prevention and treatment of obstruction in sigmoid and rectal cancer.

Patients with obstructing cancers are ineligible for preoperative chemotherapy and radiation unless they undergo surgical diversion. Endoscopic laser therapy (ELT) may provide an alternative to colostomy for these patients. We retrospectively reviewed all patients with distal sigmoid and rectal carcinomas who underwent ELT from January 1988 through April 1990. The majority of patients were referred for palliation of advanced disease. Thirty-seven patients underwent 123 ELT sessions (median, 2.5; range, one to 18). In 84% of patients, patency was maintained during a median follow-up of 31.5 weeks (range, one to 123). Morbidity and mortality were 2.5% (3/123) and 5% (1/37), respectively. Sixty-two percent had radiotherapy, chemotherapy, and/or surgery concurrent with ELT. Endoscopic laser therapy can safely and effectively reestablish and maintain luminal patency in patients with obstructing distal cancers. In addition, ELT can enable the administration of preoperative adjuvant radiotherapy and chemotherapy.

Alternating hepatic intra-arterial floxuridine and fluorouracil: a less toxic regimen for treatment of liver metastases from colorectal cancer.

Hepatic intra-arterial (HIA) infusion of floxuridine (FUDR) via an implanted pump has shown promise in the treatment of colorectal cancer metastasized to the liver. However, the potential benefit of this therapy may be offset by the high incidence of treatment-limiting biliary toxicity. Although weekly HIA bolus of fluorouracil (5-FU) is effective against metastatic colorectal cancer to the liver with no biliary toxicity, it is limited by systemic side effects. In December 1986, we began a phase II trial of alternating HIA FUDR and 5-FU via the implanted pump in an attempt to extend the duration of treatment by obviating the limiting biliary (FUDR) and systemic (5-FU) drug toxic effects. Patients received continuous HIA FUDR at 0.1 mg/kg of body weight per day on days 1 through 8 followed by an HIA bolus of 5-FU at 15 mg/kg given via the pump sideport on days 15, 22, and 29, with the cycle repeated every 35 days. Sixty-eight patients were enrolled in this trial, and 64 were fully evaluable. Of the 64 patients, 30 (47%) previously had received chemotherapy. Major response (complete response plus partial response) was observed in 32 (50%) of 64 patients, and the median survival from pump implantation in all patients was 22.4 months. In contrast to the experience with the single-agent HIA FUDR regimen, no patient had treatment terminated because of drug toxicity. Alternating HIA FUDR and 5-FU has efficacy similar to that of HIA FUDR given alone, but when closely monitored and adjusted appropriately, is not associated with toxic effects requiring treatment termination.

Chemoembolization for hepatocellular carcinoma.

Fifty-one patients with unresectable hepatocellular carcinoma (HCC) were treated with Gelfoam (absorbable gelatin sterile powder; The Upjohn Co, Kalamazoo, MI) chemoembolization. A mixture of Gelfoam powder, contrast media, and three drugs (doxorubicin, mitomycin, and cisplatin) was injected under fluoroscopic guidance via a percutaneous catheter into the hepatic artery until stagnation of blood flow was achieved. Of the 51 patients, 50 are assessable for response, and all are assessable for toxicity and complications. The median percent of liver replacement was 50% (range, 15% to 95%). By conventional response criteria, there were 12 partial responses (PRs) (24%), 13 minor responses (MRs) (26%), 12 stabilization of disease (SD) (24%), and 13 (26%) progressive disease (PD). Tumor liquefaction was noted on computed tomographic (CT) scan in 35 of 50 patients (70%). Of the 34 patients with elevated alpha-fetoprotein (AFP), 23 (68%) had a greater than 50% reduction following treatment. Responding patients were re-treated at the time of tumor progression if they still met the entry criteria. The median survival of assessable patients from the time of treatment was 207 days and from the diagnosis of the primary was 302 days. Fourteen patients remain alive at 3 months to 3 years following treatment. The vast majority of patients had transient pain, fever, nausea, and elevation in liver enzymes. Ascites developed in 14 patients. There were two treatment-related deaths: one from tumor hemorrhage and one from liver failure. Chemoembolization appears to have significant activity in patients with hepatocellular carcinoma and is relatively well tolerated.

Management of inguinal lymph node metastases from adenocarcinoma of the rectum.

Forty patients with inguinal lymph node metastases from rectal adenocarcinoma were reviewed. Patients were divided into three groups based on the extent of their disease: (1) patients with unresectable primary tumors; (2) patients with recurrent disease after abdominoperineal resection; and (3) patients with isolated inguinal lymph node metastases after abdominoperineal resection. Patients in Groups 1 and 2 underwent biopsy of their nodal metastases. Patients in Group 3 were treated by inguinal node dissection. Survival data were examined for each group, and four clinical and pathologic features were analyzed to determine their impact on prognosis: depth of invasion of the primary tumor (T1-2 vs. T3-4), number of positive lymph nodes in the rectal specimen (0-2 vs. greater than 2), extent of the inguinal lymph node metastases (unilateral vs. bilateral), and timing of the inguinal lymph node metastases (less than 1 vs. greater than 1 year after abdominoperineal resection). There were no five-year survivors in any group. Median survival was highest in those with isolated lymph node metastases, with 2 patients remaining free of disease, and was lowest in those with unresectable primary disease (7 months). Median survival was increased when inguinal LNM were unilateral (17 vs. 6 months; P less than 0.01) and when they occurred more than 1 year after abdominoperineal resection (21 vs. 7 months; P = 0.02). Stage of the primary lesion (depth of invasion and number of positive lymph nodes) did not affect survival. Of the 32 patients who underwent biopsy alone, only 1 developed a tumor-related groin complication. For patients with isolated inguinal lymph node metastases, inguinal node dissection is recommended for the purposes of local control and possible cure. For patients with extranodal disease, prophylactic excision of inguinal lymph node metastases is not warranted.

Extracorporeal hemofiltration: a model for decreasing systemic drug exposure with intra-arterial chemotherapy.

Cisplatin (3 mg/kg) was infused through the hepatic artery in nine mongrel dogs. Four of these dogs underwent simultaneous extracorporeal hemofiltration (ECH) of the hepatic venous effluent using a high-flow, dual-lumen catheter placed in the vena cava at the level of the hepatic veins. Platinum levels were measured in the plasma, urine, and ultrafiltrate and in kidney and liver tissue. ECH significantly reduced systemic drug exposure as measured by the AUC for free and total platinum, by urinary excretion, and by 24-h kidney levels. Regional liver levels were minimally affected. Recovery of platinum in the ultrafiltrate was 40% +/- 14%. ECH resulted in efficient extraction of platinum and reduced systemic drug exposure with relative preservation of regional hepatic drug exposure.

Hepatic artery infusion pumps: cannulation techniques and other surgical considerations.

Long term hepatic artery chemotherapy for metastatic disease to the liver has been made practical by technologic advances in pumps and catheters. The surgical placement of these pumps and catheters can be associated with a significant morbidity unless careful attention is given to variations in hepatic arterial anatomy and to eliminating collateral arterial supply to the distal stomach and duodenum. Gastroduodenal devascularization should be performed in all patients and should be confirmed both with intra-operative fluorescein injection and postoperative scintigraphy scanning. Routine cholecystectomy avoids the complication of chemical cholecystitis. Exact placement of the catheter tip at the junction of the gastroduodenal artery and the hepatic artery with fixation of the catheter in this position by placement of bidirectional ligatures around the catheter bead will reduce the incidence of hepatic artery thrombosis and catheter migration. Intrahepatic arterial collateralization in most patients allows for ligation of variant lobar vessels with total liver perfusion through the remaining lobar arterial supply. This again can be confirmed intra-operatively with fluorescein injection and postoperatively with scintigraphy scanning. Strict attention to these technical details will allow continued use of this important therapeutic modality in the treatment of hepatic metastases and by minimizing surgical complications will encourage continued trials to improve the efficacy of long term hepatic arterial chemotherapy.