Hepatic resection for primary or secondary malignancies with involvement of the inferior vena cava: is this operation safe or hazardous?

BACKGROUND: This study evaluated surgical techniques and results of patients with tumors who had undergone liver resection with partial resection and reconstruction of the IVC. STUDY DESIGN: We performed a retrospective analysis of all patients who underwent combined liver and IVC resection and reconstruction at a single institution. We identified 19 patients and two categories of tumors, primary (n = 8) and metastatic (n = 11). In 12 patients, a direct suture of the IVC was performed; in 3 patients a pericardium bovine patch was applied; in another 4 patients the IVC was replaced by PTFEt prosthesis. In nine patients, total hepatic vascular occlusion was required. RESULTS: Perioperative mortality was 5.9%, related to technical complications and hepatic insufficiency. Postoperative morbidity was 57.9%. Median survival time was 32 months (range 3 to 125 months). The 1-, 2-, and 5-year cumulative survival rates were 78.9%, 68%, and 49.1%, respectively. Tumor recurrence appeared in 13 patients and was the main cause of death (55.5%). Among the seven patients suffering from hepatocellular carcinoma, three are still alive at 31, 60, and 125 months after resection. In this group, 1-, 2-, and 5-year survival rates were 71.4%, 57.1%, and 38.1%. Among the 11 patients resected for colorectal liver metastases, the 1-, 2-, and 5-year survival rates were 81.8%, 62.3%, and 51.9%, respectively. CONCLUSIONS: Liver resection combined with IVC resection and reconstruction is a feasible procedure that can be performed with an acceptable operative risk leading to longterm outcome in selected patients.

Low recurrence rate of hepatocellular carcinoma after liver transplantation: better patient selection or lower immunosuppression?

BACKGROUND: Liver transplantation is currently offered to a limited number of patients with hepatocellular carcinoma (HCC) because of strict criteria introduced in the past to avoid recurrence. Immunosuppression represents a risk factor for tumor growth; the schedules of the immunosuppressant drugs have been modified through the years, aiming to reduce their dosage to the effective minimum. METHODS: A series of 106 consecutive patients with HCC who underwent transplantation over a 15-year period at a single institution was retrospectively reviewed to ascertain whether tumor recurrence was influenced by the Milano criteria presently adopted in patient selection and whether the dosage of immunosuppressant agents administered was associated with tumor recurrence. Fifteen patients who died postoperatively and 9 with a follow-up of less than 1 year were excluded; presence of the Milano criteria, tumor-node-metastasis staging, and the cumulative dosage of the single immunosuppressants given at different intervals in the first postoperative year were analyzed in the remaining 82 patients. The influence of these variables on overall and recurrence-free survival was assessed statistically. RESULTS: The Milano criteria did not influence recurrence-free survival, which was instead associated with the cumulative dosage of cyclosporine administered in the first postoperative year (93% 5-year recurrence-free survival for patients given low dosage vs. 76% for those given high dosage; P=0.01); T3 and T4 tumors did worse than T1 and T2 tumors. CONCLUSIONS: Current limits to transplantation for HCC might be reassessed in view of modified patient management; immunosuppression should be minimized in these patients.

Outcome of right hepatectomies in patients older than 70 years.

HYPOTHESIS: The increasing number of elderly patients undergoing liver resections mandates updating of clinical outcomes on this specific population. DESIGN: Case series. SETTING: A tertiary care teaching hospital. PATIENTS: Twenty-three patients older than 70 years who underwent right hepatectomies (including 7 extended right hepatectomies) between January 1, 1995, and October 31, 2001 (group 1) and 99 patients younger than 70 years who underwent 64 right hepatectomies and 35 extended right hepatectomies during the same period (group 2) were included for a total sample population of 122. MAIN OUTCOME MEASURES: Preoperative clinicopathological features, intraoperative factors, in-hospital mortality, postoperative complications, intensive care unit requirement, hospital stay, and course of main biochemical liver function test results of groups 1 and 2 were analyzed and compared. RESULTS: The 2 groups were similar for indications for surgery and the presence of underlying liver disease. Group 1 had a higher incidence of associated pulmonary diseases (21.7% vs 5%, P =.02) and patients with an American Society of Anesthesiologists score of III (ie, a patient with severe systemic disease limiting activity, but not incapacitating) (56.5% vs 26.3% of cases, P =.01). There were no differences in intraoperative requirement of packed red blood cells and in operation time. There were no in-hospital deaths in group 1; there were 2 deaths (2%) in group 2. Nine patients (39.1%) in group 1 and 32 patients (32.3%) in group 2 experienced postoperative complications (P =.53), of whom, respectively, 5 (21.7%) and 17 (17.2%) developed transient liver dysfunction (P =.56), and 4 (17.4%) and 5 (5.1%) required a supplementary intesive care unit stay (P =.06). The postoperative stay (mean [SD], 16 [14] days vs 13 [9] days, P =.88) and peak values of the aminotransferase level, total serum bilirubin level, and prothrombin time were similar in the 2 groups. The timing of the peak value of the total serum bilirubin level (mean [SD], 4.1 [4.8] days vs 2.5 [2.5] days, P =.28) and its period of normalization (mean [SD], 9.4 [10.8] days vs 6.7 [5.1] days, P =.67) were also similar for both groups. For patients with malignancies, the 3-year survival rate was 64.2% in group 1 and 53.9% in group 2 (P =.53). CONCLUSION: Being older than 70 years should not be a contraindication for major hepatectomies, provided that liver cirrhosis and severe associated medical conditions are ruled out during the preoperative evaluation.

Liver resection for multiple colorectal metastases: influence of parenchymal involvement and total tumor volume, vs number or location, on long-term survival.

HYPOTHESIS: Multiple and/or bilateral liver metastases are not absolute contraindications to surgical resection. DESIGN: Retrospective analysis. SETTING: University department of surgery and transplantation. PATIENTS AND INTERVENTION: A total of 245 curative liver resections for colorectal metastases were divided into 3 groups: M1, single lesions; M2, multiple unilobar; and M3, multiple bilobar. MAIN OUTCOME MEASURES: Univariate and multivariate analysis using several prognostic factors was performed to distinguish variables affecting long-term survival. RESULTS: Overall operative mortality was 0.8%. Overall 5-year survival was 34%. On multivariate analysis, only the percentage of hepatic involvement by the tumor significantly affected prognosis. By replacing this variable with the total tumor volume, this latter variable was the only independent predictor of survival. Patients with multiple metastases and total tumor volume less than 125 cm(3) had a significantly better outcome than patients with single nodules and total tumor volume more than 380 cm( 3). Operative mortality and morbidity were comparable among groups M1, M2, and M3. The 5-year survival was 41%, 17%, and 34%, respectively (group M1 vs M2, P =.05; group M1 vs M3 and group M2 vs M3, not significant). The 5-year survival was 41% and 23% in patients with single and multiple lesions, respectively and was 35% and 32% in patients with unilobar and bilobar lesions, respectively. CONCLUSIONS: A better outcome in patients with small single lesions was shown. In patients with multiple and/or bilateral metastases, an acceptable 5-year survival superior to 20% was obtained by surgical approach. The total volume of metastases, not number and location, seems to be the strongest predictor of survival.

Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors.

HYPOTHESIS: To minimize the incidence of ischemic arterial complications, risk factors should be clearly identified. Knowledge of the predisposing factors for such complications would make possible the institution of strict surveillance protocols that could ensure early detection of complications and so prevent the progression of ischemic damage to graft failure. DESIGN: Retrospective univariate and multivariate analysis. SETTING: University hospital. PATIENTS: Six hundred fifty-three adults who underwent 747 orthotopic liver transplantations. MAIN OUTCOME MEASURES: We used univariate and multivariate analyses to retrospectively assess the role of possible risk factors for early and late HA thrombosis (HAT) and stenosis (HAS), including etiology of liver disease, donor and recipient sex and age (aged < or =60 vs >60 years), cause of donor death, preservation solution, cold ischemic time, previous orthotopic liver transplantation, HA back-table reconstruction, direct arterial anastomosis vs interpositional conduit, experience of the surgeon, intraoperative transfusion requirements, acute rejection, and cytomegalovirus infection. RESULTS: We observed 58 ischemic complications, including 26 early HAT, 13 late HAT, and 19 HAS. Independent predictors of early HAT were donor age greater than 60 years and bench reconstruction of anatomical variants of the HA; of late HAT, arterial anastomosis fashioned using an interpositional graft of donor iliac artery (iliac conduit) and donors who died of cerebrovascular accident; and of HAS, previous orthotopic liver transplantation and cytomegalovirus infection. CONCLUSIONS: Predisposing factors for HAT mostly stem from donor and graft features. Use of iliac conduits should be limited, particularly when using old donors. Frequent screening of the arterial flow to the graft with Doppler ultrasonography is advisable in patients at risk.

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation.

OBJECTIVE: The early phase after liver transplant is considered the period of greatest risk for graft failure. In recent years breath tests have been proposed as a non-invasive method to assess liver function. In particular, the aminopyrine breath test is useful for evaluating the liver viable mass, and the methionine breath test could be used to evaluate oxidative capacity of liver mitochondria. We aimed to perform these tests in the early phase following liver transplant in order to correlate the time course of these tests to the outcome of transplantation. METHODS: Twenty-three patients undergoing liver transplant were enrolled. The methionine and aminopyrine breath tests were performed on the days 1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were expressed as the percentage of administered 13C recovered per hour and as the cumulative percentage of the 13C dose recovered over the test period. RESULTS: All but two transplants were successful in the short term and the cumulative percentage of the dose of 13C progressively increased after transplantation, reaching values not significantly different from controls (methionine at day 5). In two patients, primary non-function occurred: in these patients the cumulative percentage of the 13C dose did not increase after orthotopic liver transplant and the results of both breath tests indicated that it always remained significantly lower compared to that of other patients. CONCLUSIONS: A combination of breath tests, exploring both mitochondrial and microsomal function, could be useful in the early phase after liver transplant in order to evaluate the graft outcome.

Radical surgical treatment of recurrent hepatic hydatidosis.

BACKGROUND/AIMS: The treatment of relapsing hydatidosis must aim at the reduction of both morbidity and mortality rates and the risk of new recurrences. METHODOLOGY: Thirty-three patients with recurrence of hepatic ecchinococcosis were observed between January 1975 and May 2001. All selected patients received a first conservative surgical treatment, and recurrences developed in a period ranging from 1 to 46 years from the therapy. All patients with secondary hydatidosis were then submitted to radical surgical treatment. Ultrasound examinations, the first after 3 months from surgery, were performed to evaluate disease recurrence. Intraoperative morbidity and mortality were also evaluated. RESULTS: No intraoperative mortality was encountered. Intraoperative and postoperative morbidity were 6% and 12% respectively. During follow-up, (mean duration 53 months) no recurrences were recorded. CONCLUSIONS: Radical surgical approach is the best treatment of recurrent hydatid cysts as it represents a valid compromise between the need of a surgical radicality and a low intraoperative and postoperative morbidity.

Operative risk by the lidocaine test (MEGX) in resected patients for HCC on cirrhosis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinical usefulness of the preoperative lidocaine test (MEGX) in cirrhotic patients who were candidates for curative liver resection for hepatocellular carcinoma. METHODOLOGY: To evaluate whether MEGX was related to postoperative complications, a retrospective analysis was carried out on 51 patients, in whom a preoperative lidocaine test was available. They were divided into two groups according to a MEGX value less (22 patients, group A) or more (29 patients, group B) than 25 ng/mL. RESULTS: The two groups of patients were comparable for the preoperative clinical parameters and the surgical procedures. Patients in group A had a significantly higher rate of postoperative complications (73% vs. 28%, p < 0.005) and a tendency to a longer hospital stay, compared to patients in group B. CONCLUSIONS: The lidocaine value is an effective index of hepatic function. A preoperative MEGX value lower than 25 ng/dL in cirrhotic patients was related to a significantly higher risk of liver insufficiency and postoperative complications after hepatic resection.

Liver metastases from colorectal cancer: present surgical approach.

BACKGROUND/AIMS: New developments in surgical techniques and strategies are modifying the indications to resection of liver metastases. METHODOLOGY: From January 1986 to December 2000, 246 consecutive patients with colorectal liver metastases underwent curative hepatic resection. Surgical strategies included simultaneous resection of primary and metastatic colorectal tumor, re-resection of colorectal liver recurrences, two-stage resection and resection of the inferior vena cava when involved by the tumor. Disease-free survival in relation to clinical, pathological and surgical factors was retrospectively assessed with univariate and multivariate analyses. RESULTS: The overall operative mortality was 0.8%. The 1-, 3- and 5-year disease-free survival rates were 75%, 47% and 40%, respectively. Tumors larger than 7 centimeters, multiple lesions, tumors involving more than 2 segments and those requiring major hepatectomy had a worse prognosis at univariate analysis. A size of the tumor above 7 centimeters was the only independent prognostic factors at multivariate analysis. Two-stage and inferior vena cava resection increased operability; re-resection of recurrent colorectal secondaries prolonged survival. CONCLUSIONS: Resection of colorectal liver metastases is safe and effective; it should be considered the treatment of choice for this disease and proposed even for advanced lesions. Counseling of the hepatobilary surgeon should be asked for once a liver secondary is detected in the preoperative work-up of a colorectal cancer.

Influence of prognostic factors on the outcome of liver transplantation for hepatocellular carcinoma on cirrhosis: a univariate and multivariate analysis.

BACKGROUND/AIMS: Hepatocellular carcinoma is related to liver cirrhosis in 70-85% cases. During the '80s, the best treatment was represented by liver resection. Recently, liver transplantation has been introduced as an optimal therapeutic alternative. The purpose of this study is to select the best candidates for liver transplantation considering several prognostic factors that are related to tumor characteristics. METHODOLOGY: Among 573 liver transplantations, we have retrospectively analyzed 87 patients undergoing liver transplantation for hepatocellular carcinoma on cirrhosis; in 30 (34.5%) patients, hepatocellular carcinoma was an incidental finding in the surgical specimen. RESULTS: Operative mortality was 2.2% (2/87). Twenty-five patients died during the follow-up. The main cause of death was represented by tumor recurrence in 10.3% of cases. The 3-year and 5-year overall survival was 71.6% and 66.2% respectively. On a univariate analysis, the only variable significantly related with overall-survival was alpha-fetoprotein levels (p=0.01). Furthermore, alpha-fetoprotein, the diameter of tumor greater than 3 cm, the presence of satellite nodules, Edmonson's grade III-IV, micro-macro vascular thrombosis, and TNM stadium III-IV were significantly related with the development of tumor recurrence. On a multivariate analysis, only alpha-fetoprotein (p=0.01, Risk ratio = 2.7) resulted as a risk independent factor of patient overall-survival; vascular invasion (p=0.02, Risk ratio = 2.1) was predictive of tumor recurrence. CONCLUSIONS: Liver transplantation is a good therapeutic option in a selected group of patients, with a small nodule (<3 cm), low alpha-fetoprotein levels (<20 ng/mL), with absence of micro-macro vascular thrombosis in which conventional liver resection is unfeasible.

Simultaneous presence of focal nodular hyperplasia and hepatocellular carcinoma: case report and review of the literature.

Focal nodular hyperplasia (FNH) is an infrequent benign tumor of the liver that is generally believed to have no potential for malignant transformation; the coexistence of FNH and hepatocellular carcinoma (HCC) has seldom been reported. Here we describe an exceptional case of simultaneous FNH and HCC in the same patient and discuss the clinical and therapeutic management of FNH on the basis of a review of the literature.

Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat.

BACKGROUND: Optimization of the conditions for regeneration is a major goal in the management of patients with acute liver failure (ALF). Previous observations suggested that hyperoxygenation of the liver may improve its regenerative capacity. Thus, this study aimed to determine whether an additional supply of oxygenated blood achieved by portal vein arterialization (PVA) is protective in rat ALF caused by toxin administration or hepatectomy. METHODS: Sprague-Dawley rats were subjected or not to PVA after CCl(4) intoxication or extended hepatectomy. PVA was performed by interposing a stent between the left renal artery and splenic vein after left nephrectomy and splenectomy. Liver injury was evaluated by the serum ALT level and necrotic cell count. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine (BrdU) staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. In the CCl(4)-induced ALF, serum ALT levels and necrosis were significantly reduced in arterialized than non-arterialized rats. PVA greatly promotes liver regeneration in both models. Finally, PVA significantly improved survival compared to controls (CCl(4): 100 versus 40%; 90% hepatectomy: 90 versus 30%). Interestingly, in the CCl(4)-induced ALF, survival was 100% even when the shunt was closed after 48 h. CONCLUSION: These data indicate that the additional supply of arterial oxygenated blood through PVA promotes a rapid regeneration leading to the resolution of toxic-induced massive liver necrosis and a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool for optimizing hepatocyte regeneration.

Venous outflow reconstructions with the piggyback technique in liver transplantation: a single-center experience of 431 cases.

The ideal method of venous outflow reconstruction with the piggyback technique (PB) in orthotopic liver transplantation (OLT) is not well-established. The complications related to PB in 431 primary OLTs were analyzed comparing the orifices used for the anastomosis (cuff of the recipient left and middle hepatic veins [LM], LM with a >1 cm cavoplasty [LM+], or also including the right hepatic vein [LMR]). Treatment strategies and outcome were also evaluated. Twenty patients (4.6%) experienced complications: 13 of 120 (10.8%) with LM, four of 225 (1.8%) with LM+, and three of 86 (3.5%) with LMR (LM versus LM+: P < 0.0001; LM versus LMR: P = NS; LM+ versus LMR = NS). Balloon dilation was successful in 10 of 13 cases in which it was attempted (77%). Eight patients required retransplantation (40%). Three patients (0.7%) died from causes linked to stenosis. Five-year survival of patients with and without complications was 75% and 79%, respectively (P =NS); 5-year graft survival was 50% and 76%, respectively (P = 0.001). The stump formed by the recipient left and middle hepatic veins with a transversal incision >1 cm of the caval wall constantly provides an adequate width for the caval anastomosis with the PB.

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression.

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.

Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis.

BACKGROUND/AIMS: Recurrence of hepatocellular carcinoma (HCC) following surgical resection is influenced by parameters detectable on the resection specimen or through a biopsy. The prognostic significance of HCC doubling time (DT) after surgery has never been investigated. METHODS: We evaluated 62 patients who underwent curative resection of a single HCC on cirrhosis; tumors were assessed before surgery on two subsequent occasions with the same imaging technique allowing the calculation of DT. The influence of tumor DT, clinical and pathological parameters on recurrence-rate and patients survival was assessed with uni- and multivariate analysis. Relationship between DT and pathological features was also analyzed. RESULTS: Three-year recurrence rate was 32.3% (20 patients): this was significantly higher in the presence of DT shorter than 100 days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59 versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when well/moderately differentiated; P=0.015). DT was the only independent predictor of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only. DT was significantly shorter in tumors with microvascular invasion (P=0.007), undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011). CONCLUSIONS: DT is easy to estimate and indicates the prognosis of single HCCs prior to liver resection.

Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience.

Despite satisfactory overall results reported, early post-operative period after liver transplantation (LT) still represents a critical time with persistently high rate of graft loss. We retrospectively reviewed our experience of 17 yr in LT, analysing the impact on grafts and patient survivals of the acute complications affecting the graft in the early period following LT. To evaluate the changes that occurred over the years in case of early acute graft failure (EAGF), the study population was divided into three equal groups of 223 patients corresponding to three different periods. Ninety (13.5%) experienced an EAGF. Causes of EAGF were hepatic artery thrombosis (HAT) in 32 cases (4.8%), primary graft non-function in 29 cases (4.3%), caval stenosis in 19 (2.8%), early irreversible acute rejection in 6 (0.9%) and portal vein thrombosis in 4 (0.6%). The use of elderly donors and the introduction of the piggyback technique proved to be associated with a higher incidence of HAT and caval stenosis, respectively. Female recipients of male donors were independently associated with Primary graft non-function. Of 90 patients with EAGF, 20 (22.2%) died within the first month after LT, 34 (37.8%) underwent retransplantation (ReLT) and 36 (40%) received conservative treatment. Conservative treatments increased from 3.6% in the first group to 47.0 and 66.8% in the second and third one (p = 0.000). One-year graft and patient survival of patients with EAGF significantly improved over the three eras analysed. The incidence of EAGF remains consistent. Nevertheless, a better understanding of the clinical situations and changes in treatment strategies have led to significant improvements in terms of graft and patient survival rates, now close to the survival rate of EAGF-free patients.

Outcome of pregnancy after organ transplantation: a retrospective survey in Italy.

The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy.