Alberto Morabito

Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with Cirrhosis

BACKGROUND The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. METHODS We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. RESULTS The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. CONCLUSIONS Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial

BACKGROUND The use of elective regional node dissection in patients with cutaneous melanoma without any clinical evidence of metastatic spread is still debated. Our aim was to evaluate the efficacy of immediate node dissection in patients with melanoma of the trunk and without clinical evidence of regional node and distant metastases. METHODS An international multicentre randomised trial was carried out by the WHO Melanoma Programme from 1982 to 1989. The trial included only patients with a trunk melanoma 1.5 mm or more in thickness. After wide excision of primary melanoma, patients were randomised to either immediate regional node dissection or a regional node dissection delayed until appearance of regional-node metastases. FINDINGS Of the 252 patients entered, 240 (95%) were eligible and evaluable for analysis. 122 of these were randomised to immediate node dissection. 5-year survival observed in patients who had delayed node dissection was 51.3% (95% CI 41.7-60.1) compared with 61.7% (52.0-70.1) of patients who had immediate node dissection (p=0.09). 5-year survival rate in patients with occult regional node metastases was 48.2% (28.0-65.8) and 26.6% (13.4-41.8, p=0.04) in patients in whom the regional node dissection was delayed until the time of appearance of regional node metastases. Multivariate analysis showed that routine use of immediate node dissection had no impact on survival (hazard ratio 0.72, 95% CI 0.5-1.02), whilst the status of regional nodes affected survival significantly (p=0.007). The patients with regional nodes that became clinically and histologically positive during follow-up had the poorest prognosis. INTERPRETATION Node dissection offers increased survival in patients with node metastases only. Sentinel node biopsy may become a tool to identify patients with occult node metastases, who could then undergo node dissection.

Inefficacy of Immediate Node Dissection in Stage 1 Melanoma of the Limbs

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clarks level or Breslows thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.

Survival and prognostic indicators in compensated and decompensated cirrhosis

Six-year survival of cirrhosis was assessed in a series of 1155 consecutive patients (751 men, 404 women). Among the men, 33% were alcoholics and 18% were HBsAg positive; corresponding figures for the women were 15% and 6%, respectively. Features of decompensation at first presentation were observed in 63% of the patients. Six-year survival was 54% in compensated and 21% in decompensated patients. No significant differences in survival were found between alcoholics and nonalcoholics. Leading causes of death were liver failure (49%), hepatocellular carcinoma (22%), and bleeding (13%). The prognostic role of 21 variables was evaluated separately in compensated and decompensated patients by the Coxs regression model. The following variables were found to be significant predictors of death risk in compensated patients: male sex, HBsAg positivity, age, prothrombin time prolongation, and esophageal varices. In decompensated disease the significant indicators of death risk were: hepatocellular carcinoma, encephalopathy, hemorrhage, SGOT, esophageal varices, gamma globulins, prothrombin time prolongation, continued abuse of alcohol, HBsAg positivity, gamma glutamyl transpeptidase, and cholinesterase. A simple prognostic index based upon the relative risk coefficient of the significant variables is suggested.

Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities

Results of a prospective randomized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported. Five‐hundred‐fifty‐three Stage I patients whose limbs were affected entered the study; 267 were submitted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinically positive nodes were detected. Survival curves of the two treatment groups could be superimposed. No subsets of patients benefitted from immediate node dissection. The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months. If the quarterly follow‐up is not guaranteed, immediate node dissection is advisable, at least for melanomas thicker than 2 mm.

Thin Stage I Primary Cutaneous Malignant Melanoma

Although wide surgical excision is the accepted treatment for thin malignant melanomas, there is reason to believe that narrower margins may be adequate. We conducted a randomized prospective study to assess the efficacy of narrow excision (excision with 1-cm margins) for primary melanomas no thicker than 2 mm. Narrow excision was performed in 305 patients, and wide excision (margins of 3 cm or more) was performed in 307 patients. The major prognostic criteria were well balanced in the two groups. The mean thickness of melanomas was 0.99 mm in the narrow-excision group and 1.02 mm in the wide-excision group. The subsequent development of metastatic disease involving regional nodes and distant organs was not different in the two groups (4.6 and 2.3 percent, respectively, in the narrow-excision group, as compared with 6.5 and 2.6 percent in the wide-excision group). Disease-free survival rates and overall survival rates (mean follow-up period, 55 months) were also similar in the two groups. Only three patients had a local recurrence as a first relapse. All had undergone narrow excision, and each had a primary melanoma with a thickness of 1 mm or more. The absence of local recurrence in the group of patients with a primary melanoma thinner than 1 mm and the very low rate of local recurrences indicate that narrow excision is a safe and effective procedure for such patients.

The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients†

Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA–seropositive patients with Child‐Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations. During 114 months (range 1–199), hepatocellular carcinoma (HCC) developed in 68 (32%), ascites in 50 (23%), jaundice in 36 (17%), upper gastrointestinal bleeding in 13 (6%), and encephalopathy in 2 (1%), with annual incidence rates of 3.9%, 2.9%, 2.0%, 0.7%, and 0.1%, respectively. Clinical status remained unchanged in 154 (72%) and progressed to Child‐Pugh class B in 45 (21%) and class C in 15 (7%). HCC was the main cause of death (44%) and the first complication to develop in 58 (27%) patients, followed by ascites in 29 (14%), jaundice in 20 (9%), and upper gastrointestinal bleeding in 3 (1%). The annual mortality rate was 4.0% per year and was higher in patients with other potential causes of liver disease than in those without them (5.7% vs. 3.6%; P = .04). In conclusion, hepatitis C–related cirrhosis is a slowly progressive disease that may be accelerated by other potential causes of liver disease. HCC was the first complication to develop and the dominant cause for increased mortality. (HEPATOLOGY 2006;43:1303–1310.)

Percutaneous etharrol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients

In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Childs Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male‐female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow‐up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1‐year, 2‐year, and 3‐year survival percentages (by the Kaplan‐Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Childs class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1‐year, 2‐year, and 3‐year survival rates for patients with more than one HCC were 90%, 67%, and 31%, respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy‐to‐do, and low‐cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful. Cancer 1992; 69: 925–929.

Adjunctive Systemic Hyperbaric Oxygen Therapy in Treatment of Severe Prevalently Ischemic Diabetic Foot Ulcer: A randomized study

OBJECTIVE To evaluate the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer. RESEARCH DESIGN AND METHODS From August 1993 to August 1995, 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers. All the subjects underwent our diagnostic-therapeutic protocol and were randomized to undergo s-HBOT. Two subjects, one in the arm of the treated group and one in the arm of nontreated group, did not complete the protocol and were therefore excluded from the analysis of the results. Finally, 35 subjects received s-HBOT and another 33 did not. RESULTS Of the treated group (mean session = 38.8 ± 8), three subjects (8.6%) underwent major amputation: two below the knee and one above the knee. In the nontreated group, 11 subjects (33.3%) underwent major amputation: 7 below the knee and 4 above the knee. The difference is statistically significant (P = 0.016). The relative risk for the treated group was 0.26 (95% CI 0.08–0.84). The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy: 14.0 ± 11.8 mmHg in treated group, 5.0 ± 5.4 mmHg in nontreated group (P = 0.0002). Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT (odds ratio 0.084, P = 0.033, 95% CI 0.008–0.821) and indicated as negative prognostic determinants low ankle-brachial index values (odds ratio 1.715, P = 0.013, 95% CI 1.121–2.626) and high Wagner grade (odds ratio 11.199, P = 0.022, 95% CI 1.406–89.146). CONCLUSIONS s-HBOT, in conjunction with an aggressive multidisciplinary therapeutic protocol, is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers.

US-Elastography in the Differential Diagnosis of Benign and Malignant Thyroid Nodules

BACKGROUND Ultrasound (US)-elastography is a newly developed imaging technique for the reconstruction of tissue stiffness by measuring the degree of tissues deformation in response to the application of an external force. This technique has previously been shown to be useful in the differential diagnosis between benign and malignant tumors. METHODS The objective of this study was to assess the diagnostic accuracy of US-elastography in the differential diagnosis of thyroid cancer, using the cytologic/histopathologic analysis as the reference standard. A total of 67 consecutive patients with thyroid nodules who were referred to the Thyroid Unit at the Policlinico MultiMedica were enrolled in this prospective study between January and December 2006. Eighty-six nodules in these patients were examined by US B-mode, US color-power-Doppler, and US-elastography. Nodules were subjected to fine-needle aspiration biopsy and patients with a reading of malignant or indeterminate had thyroid surgery. The final diagnosis was based on the cytology reading in those who did not have surgery and the histopathology reading in those who had surgery. US-elastography scores were based on four classes of tissue stiffness (class 1 for soft nodules; class 2 and 3 for nodules with an intermediate degree of stiffness; class 4 for anelastic lesions). RESULTS Seventeen nodules were malignant and 69 were benign. Sensitivity and specificity of the US-elastography for thyroid cancer diagnosis were 94.1% (16/17) and 81% (56/69), respectively. The positive and negative predictive values were 55.2% (16/29) and 98.2% (56/57), respectively. The accuracy of the technique was 83.7%. CONCLUSION US-elastography is a promising technique that, combined with other US modalities, is easy and rapid to perform and can help to identify thyroid nodules that are likely to be malignant. An important limitation is probably lack of sensitivity for follicular thyroid carcinoma.