Vanderbilt experience with cryosurgery for 25 advanced hepatic tumors.

There are reports that suggest cryosurgical techniques may be a useful adjunct or even a viable alternative to surgical resection for hepatobiliary malignancies. Our objective was to evaluate the clinical results following cryoablation in conjunction with surgical resection for advanced hepatic tumors. Cryosurgical techniques were used in 25 consecutive patients with advanced liver tumors (1) to achieve a > 1-cm tumor-free margin when standard surgical margins were close, (2) to manage multiple tumor nodules with or without standard surgical resection, or (3) to increase chemotherapy response rates in conjunction with hepatic arterial portocath placement. In these 25 patients cryoablation was applied to 44 of 91 lesions--independently in four patients and in combination with hepatic resection in 21 patients. Cryoablation was used in seven patients because of close surgical margins. In 18 patients cryosurgery was used for complete lesion ablation. In 14 of the 18 patients cryosurgery and resection were used for different lesions; in four cryosurgery alone was used. Transient changes in hepatic enzymes, PT, PTT, and platelets were at maximum on postoperative days 1 to 3. Surgical mortality and morbidity rates were 4% and 68% respectively. Coagulation abnormalities were common; at least 30% reduction in platelets occurred in all patients and a > 50% reduction occurred in 15 of 25 (60%). Sixteen patients had a PT > 15 sec and five of these 16 also had platelet count < 50,000. Associated complications included one wound hematoma, one GI hemorrhage, one intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site. 96%, 66%, 49%, 35%, and 20% of patients were surviving respectively at 6, 12, 18, 24, and 36 months. This report helps define the risks and results of cryosurgical ablation in conjunction with surgical resection for very advanced hepatobiliary tumors. Management of lesions contiguous to major blood vessels can include the Pringle maneuver or total hepatic vascular isolation. Cryoablation can be applied carefully as a complement to resection to achieve total tumor ablation in selected otherwise unresectable patients.

Clinical experience with cryosurgery for advanced hepatobiliary tumors.

INTRODUCTION: There have been reports that suggest cryosurgical techniques may be a useful adjunct to surgical resection or even a viable alternative treatment for hepatobiliary malignancies. Our objective was to evaluate the clinical results following cryoablation in conjunction with surgical resection for advanced hepatic tumors. MATERIALS AND METHODS: Thirty-two consecutive procedures in 31 patients with advanced liver tumors treated with cryosurgical ablation were evaluated. Cryosurgery was applied: (1) to achieve a > 1-cm tumor-free margin when standard surgical margins were close (2) with or without standard surgical resection to manage multiple tumors (3) with hepatic arterial portocath placement to increase tumor response. Cryoablation was applied to 47 of 105 lesions--independently in 4 patients and in combination with hepatic resection in 28 procedures. RESULTS: Cryoablation was used in 11 procedures because of close surgical margins. In 21 operations cryosurgery was used for primary ablation. In 17 of these 21 patients both cryosurgery and resection were used for different lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes, PT, PTT, and platelets were at maximum on Postoperative Days 1-3. Surgical mortality and morbidity rates were 6 and 60%, respectively. Coagulation abnormalities were common: at least 30% reduction in platelets occurred in all patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty patients had a PT > 15 s and 6 of these 20 also had a platelet count < 50,000. Associated complications included one wound hematoma, two GI hemorrhages, one intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site. The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36 months, respectively. CONCLUSIONS: This report helps define the risks and results of cryosurgical ablation as a complement to surgical resection for advanced hepatobiliary tumors. Management of lesions contiguous to major blood vessels may include either the Pringle maneuver or total vascular isolation. Since these procedures can have significant morbidity, we urge cautious application of cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable patients.

Experience with neoral versus sandimmune in primary liver transplant recipients.

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 +/- 1.9 days in the Neoral group vs 7.8 +/- 4.9 days in the Sandimmune group. (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13%) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year post-transplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70% using Sandimmune.

Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors.

BACKGROUND: Patients with advanced metastatic carcinoid tumors who have disease progression despite conventional therapy are left with few therapeutic options. Hepatic artery chemoembolization (HACE) may play a role in palliating these patients' symptoms. METHODS: Fifteen patients with biopsy-proven advanced bilobar hepatic carcinoid metastases who demonstrated progression of symptoms and/or tumor size despite treatment with somatostatin analogues were treated with intra-arterial chemotherapy and HACE to determine efficacy and safety. Five days of intra-arterial 5-fluorouracil (1 g/m2) were followed by HACE with adriamycin (60 mg), cisplatin (100 mg), mitomycin C (30 mg), and polyvinyl alcohol (Ivalon); 200 micron to 710 micron). Patients were continued on octreotide at the same dose (150 to 2000 microg subcutaneous q 8 hours) before, during, and after the procedure. RESULTS: Efficacy of treatment was assessed by comparing pretreatment and 3-month clinical, laboratory, radiographic, and quality of life parameters. Symptoms were improved in 8 of 12 patients who had diarrhea, 7 of 12 who had flushing, 9 of 12 who had abdominal pain, and in 4 of 7 who had malaise. Elevated tumor markers decreased in all patients. Biochemical markers (mean +/- SE) at 3 months decreased by 60% +/- 6% for 5-HIAA, 75% +/- 10% for chromogranin A and 50% +/- 7% for neuron-specific enolase. Tomographic assessment revealed tumor liquefaction in 10 of 13 patients. The Karnofsky performance status improved from a mean of 66 +/- 2 to 84 +/- 2 (P <0.001). Median follow-up was 16 months, with 13 deaths occurring from 1 week to 71 months after treatment. CONCLUSIONS: Hepatic artery chemoembolization improves symptoms of carcinoid syndrome, has a high tumor response rate, and improves short-term quality of life in this group of patients with advanced hepatic carcinoid disease.

Nashville experience with liver transplantation in Veterans Administration patients.

In this study, we compared results of 28 liver transplants performed in 25 patients referred through the Veterans Administration with 82 transplants performed in 75 nonveteran patients. The evaluation and follow-up care was provided by the same team of physicians and nurses and the transplant procedure performed in the same hospital for both patient groups. There was a significantly greater incidence of hepatitis C and/or previous alcohol abuse in veteran compared with non-VA patients [23/25 (92%) vs 29/75 (39%); P < 0.05] and a greater incidence of native portal vein thrombosis [6/25 (24%) vs 2/75 (2.6%); P < 0.01], but no difference in Child's-Pugh score (10.8 vs 9.9) or UNOS listing status (mean status 2.7 vs 2.8). The increased incidence of native portal vein thrombosis did not appear to be solely related to previous alcohol abuse or hepatitis C, since only 1 of 29 (3.4%) non-VA patients with these etiologies had this finding. There was no difference in patient or graft survival between the VA and non-VA groups with overall actuarial 6-, 12-, and 18-month patient survival of 86, 84, and 83% and graft survival of 80, 78, and 77%. There was no difference in major complication rates but there was a significantly longer average hospital stay (27 +/- 31 vs 18 +/- 12 days; P < 0.05) in the VA compared with non-VA group. One patient with native portal vein thrombosis in the non-VA group developed portal vein thrombosis in the postoperative period. There was no documented recidivism in any patient with a history of prior substance abuse in either group. This study confirms that veteran patients have a higher incidence of hepatitis C and previous alcohol abuse as causes of liver disease, have a higher incidence of native portal vein thrombosis, and have longer mean hospital stays, but experience the same survival in the first 18 months compared with nonveteran patients.

Repeat hepatic surgery for colorectal cancer metastasis to the liver.

OBJECTIVE: The authors addressed whether a repeat hepatic operation is warranted in patients with recurrent isolated hepatic metastases. Are the results as good after second operation as after first hepatic operation? SUMMARY BACKGROUND DATA: Five-year survival after initial hepatic operation for colorectal metastases is approximately 33%. Because available alternative methods of treatment provide inferior results, hepatic resection for isolated colorectal metastasis currently is well accepted as the best treatment option. However, the main cause of death after liver resection for colorectal metastasis is tumor recurrence. METHODS: Records of 95 patients undergoing initial hepatic operation and 10 patients undergoing repeat operation for isolated hepatic metastases were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. The literature on repeat hepatic resection for colorectal metastases was reviewed. RESULTS: The mean interval between the initial colon operation and first hepatic resection was 14 months. The mean interval between the first and second hepatic operation was 17 months. Operative mortality was 0%. At a mean follow-up of 33 +/- 27 months, survival in these ten patients was 100% at 1 year and 88% +/- 12% at 2 years. Disease-free survival at 1 and 3 years was 60% +/- 16% and 45% +/- 17%, respectively. After second hepatic operation, recurrence has been identified in 60% of patients at a mean of 24 +/- 30 months (median 9 months). Two of these ten patients had a third hepatic resection. Survival and disease-free survival for the 10 patients compared favorably with the 95 patients who underwent initial hepatic resection. CONCLUSIONS: Repeat hepatic operation for recurrent colorectal metastasis to the liver yields comparable results to first hepatic operations in terms of operative mortality and morbidity, survival, disease-free survival, and pattern of recurrence. This work helps to establish that repeat hepatic operation is the most successful form of treatment for isolated recurrent colorectal metastases.