Marcello Schiavo

Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: A prospective study

Objective:Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT). Background:RFA has become the elective treatment of local control of HCC, although histologic data supporting radiologic assessment of response are rare and prospective studies are lacking. Prognostic impact of repeated RFA for HCC persistence is also undetermined. Methods:Percentage of RFA-induced necrosis and tumor persistence-rate at various intervals from treatment was studied in 60 HCC (median: 3 cm; Milan-Criteria IN: 80%) isolated in 50 consecutive cirrhotic patients undergoing OLT. Single-session RFA was the only treatment planned before OLT. Histologic response determined on explanted livers was related to 28 variables and to pre-OLT CT scan. Results:Mean interval RFA→OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC ≤3 cm. Tumor size was the only prognostic factor significantly related to response (P = 0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA and significantly correlated with HCC >3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%. Conclusions:RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

Prevention of hepatocellular carcinoma recurrence with alpha‐interferon after liver resection in HCV cirrhosis

Tumor recurrence after resection of hepatocellular carcinoma (HCC) can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Interferon (IFN) has the potential for chemoprevention against hepatitis C virus (HCV)‐related cirrhosis. A predetermined group of 150 HCV RNA–positive patients undergoing resection of early‐ to intermediate‐stage HCC was stratified into 80 HCV‐pure (hepatitis B anticore antibody [anti‐HBc]–negative) and 70 mixed HCV+hepatitis B virus (HBV) (anti‐HBc–positive) groups, then randomized to IFN‐α (3 million units 3 times every week for 48 weeks [n = 76]) versus control (n = 74). The primary end point was recurrence‐free survival (RFS); secondary end points were disease‐specific and overall survival. Intention‐to‐treat and subgroup analysis on adherent patients were conducted. Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis. No patient experienced life‐threatening adverse events. There were 28 adherent patients (37%). After 45 months of median follow‐up, overall survival was 58.5%, and no significant difference in RFS was detectable between the two study arms (24.3% vs. 5.8%; P = .49). HCC recurred in 100 patients (48 IFN‐treated, 52 controls), with a 50% reduction in late recurrence rate in the treatment arm. HCC multiplicity and vascular invasion were significantly related to recurrence (P = .01 and .0003). After viral status stratification, while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences (72 events), there was a significant benefit on late recurrences (28 events) in HCV‐pure patients adherent to treatment (HR: 0.3; 95% CI: 0.09–0.9; P = .04). In conclusion, IFN does not affect overall prevention of HCC recurrence after resection, but it may reduce late recurrence in HCV‐pure patients receiving effective treatment. (HEPATOLOGY 2006;44:1543–1554.)

The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry.

Background:Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. Material and Methods:Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7–369) from moment of diagnosis and a median of 78.5 (range, 1–245) from the moment of LT. Results:HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6–98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. Conclusions:The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

Results of EUS in detecting perirectal lymph node metastases of rectal cancer: the pathologist makes the difference ☆ ☆☆

BACKGROUND Accurate preoperative staging of primary rectal cancer is mandatory because the result may affect therapeutic decisions. Endoscopic ultrasonography (EUS) is considered the most accurate method for locoregional staging, but the issue of possible variations in the assessment of its accuracy related to technical aspects of pathologic staging has never been raised. The aim of this study was to assess EUS results as determined by two different methods of dissection of surgical specimens. METHODS Among all cases with primary rectal cancer staged with EUS from April 1991 to April 1997, 131 patients underwent surgery without preoperative radiotherapy; EUS results for nodal staging were compared with those obtained by pathology. Resected specimens were examined using two different techniques (conventional vs. special dissection). RESULTS There was a significant decrease in diagnostic accuracy of EUS according to pathologic technique. Overall accuracy, sensitivity, specificity, positive and negative predictive values for conventional versus special dissection were as follows: 74.6% vs. 43. 3% (p = 0.0001), 67.8% vs. 21.8% (p = 0.0002), 79.1% vs. 67.8% (p = 0.14), 67.8% vs. 43.7% ( p = 0.02), and 79.1% vs. 43.2% (p = 0.0003), respectively. EUS sensitivity according to size of metastatic lymph nodes was significantly lower for nodes smaller than 5 mm in diameter (p = 0.025) when special dissection was performed because of a larger number of lymph nodes harvested. CONCLUSIONS Our findings raise concern about the results of EUS staging of lymph node metastases in rectal cancer. Further prospective studies on a node-by-node basis could clarify the real diagnostic yield of EUS.

Preoperative radiation therapy for patients with T2–T3 carcinoma of the middle-to-lower rectum

The aim of this study was to determine the effects of preoperative radiation therapy (RT) on the objective responses of patients with rectal carcinoma to their treatment. These effects were assessed with endorectal ultrasound (EUS) evaluation, histopathologic grading of postirradiation tumor mass reduction in the surgical specimen, and analysis of local and distant recurrences.

Fibroblastic reticular cell tumor of the spleen: report of a case and review of the entity

Fibroblastic reticulum cells (FBRCs) are stromal support cells located in the parafollicular area and deep cortex of lymph nodes and in the extrafollicular areas of the spleen and tonsils. We report a case of malignant FBRC tumor of the spleen occurring in a 61-year-old woman. Two years after splenectomy, multiple hepatic lesions were found, which were resected. Histologically, the tumor showed similar morphological features in the spleen as in the liver metastases. There was a whorled pattern of oval and spindle cells in a collagenized background admixed with an inflammatory cell infiltrate composed of lymphocytes and plasma cells. The tumor cells were positive for common muscle actin, smooth muscle actin, and focally for CD68. In situ hybridization for Epstein Barr virus was negative. To the best of our knowledge, this is the first report of malignant FBRC tumor arising in the spleen. The differential diagnosis of splenic tumors with inflammatory pseudotumor-like features is discussed.

Preoperative endoscopic ultrasonography in patients with gastric cancer.

Aims and background There is a need to assess the accuracy of endoscopic ultrasonography (EUS) in the diagnosis and staging of gastric cancer, especially in the early and very advanced stages of the disease when the therapeutic approach is still controversial. Methods A retrospective study was performed on 79 patients with gastric cancer in order to compare the stage defined by preoperative EUS with that assessed histopathologically. All patients underwent laparotomy for final diagnosis, staging, and eventually treatment. The results of EUS were correlated with the histologic findings of the resected specimens. Results In the uT1 group, which corresponds to early gastric cancer, the diagnosis was histologically confirmed in 85.7% of the cases. In patients with advanced tumors defined as uT3-uT4, i.e., tumors infiltrating the serosa or neighboring structures, the diagnostic concordance was 91.1%. In contrast, concordance for less advanced lesions confined to the muscular layer was only 31.2%. As regards the lymph nodes, they were defined metastatic in 31 patients and confirmed to be histologically involved in 77.4%. In contrast, when the lymph nodes were assessed as negative at EUS, they proved to be metastatic in more than half the cases. Conclusions From the data it appears that EUS has proven to be valuable in correctly staging most of the patients. EUS shows not only tumor depth and local spread but also the passage from a pathologic to a normal wall and lymph node metastasis. EUS appears to represent an important advance in the staging and follow-up of patients with gastric cancer. Instruments and techniques will continue to evolve, but the next level of research should be designed to show that the improved staging provided by EUS has clinical utility and can affect patient outcome. It is noteworthy that the highest accuracy of EUS has been shown in those conditions (uT1 and uT3-4) which currently are under consideration for a therapeutic approach that differs from the standard one.

CT cholangiography: Assessment of feasibility and diagnostic reliability

OBJECTIVE To assess the reliability of computed tomography (CT) cholangiography in evaluating the anatomy of the intrahepatic biliary ducts. MATERIALS AND METHODS Twenty-eight patients underwent CT cholangiography at the National Cancer Institute of Milan, Italy. Twenty-one patients were candidates for liver surgery and seven had suspected postoperative biliary complications. The patients had not dilatation of the intrahepatic biliary ducts at US examination and bilirubin levels were not higher than 2 mg/dl. To define the reability of the CT cholangiography, a scoring system (from 0 to 3) was used for each order of biliary branches. RESULTS In all cases, it was technically possible to carry out the CT cholangiography according to the protocol. There were no adverse reactions to the contrast agent. Two radiologists gave the maximum score of 3 for visualisation of the first- and second-order biliary branches in all cases. For visualisation of third- and fourth-order biliary branches the maximum score of 3 was given in 18 patients, a score of 2 in 8 patients and a score of 1 in 2 patients. Three anatomical variants of biliary ducts were detected. CT cholangiography was diagnostic in all seven cases of suspected postoperative biliary complications. CONCLUSION Our work confirms the high spatial resolution and reability of CT cholangiography in evaluating the intrahepatic biliary anatomy of patients who are candidates for liver surgery, with non-dilated biliary ducts and with bilirubin levels no higher than 2 mg/dl.

L'ENDOSCOPIA NELLA DIAGNOSI E STADIAZIONE DEL CARCINOMA PANCREATICO

Pancreatic carcinoma is the fourth cause of death for cancer in the USA, carrying a dismal prognosis and poor overall survival. Unfortunately, resection for cure is feasible in a limited number of patients, thus confirming the need for an early diagnosis and accurate preoperative staging to select patients potentially resectable from those candidates to palliative treatment. Among imaging modalities, endoscopic procedures (endoscopic retrograde cholangiopancreatography, laparoscopy and endoscopic ultrasonography) play a key role in the diagnosis and staging of pancreatic tumors. Endoscopic retrograde cholangiopancreatography (ERCP) allows direct visualization of the main pancreatic duct and its side branches with their morphologic alterations, which are present in most cases of pancreatic cancer. The method is very sensitive in experienced hands, with diagnostic accuracy over 95%. The most common finding in pancreatic cancer is the stricture of the pancreatic duct, the bile duct, or both. Moreover, ductal brush cytology and K-ras mutation analysis can be performed during ERCP, possibly improving the diagnostic accuracy of the technique. Diagnostic laparoscopy provides detection of small (<1 cm) liver metastases and peritoneal implants of tumor which cannot be visualized by any other imaging modality, with the possibility to biopsy under direct vision suspicious areas or to perform peritoneal lavage. The adjunct of laparoscopic ultrasound improves the staging capabilities of the technique for pancreatic cancer (retroperitoneal spread, vascular invasion). Endoscopic ultrasonography (EUS) is able to produce great detail of the pancreatic parenchyma and regional lymph nodes. It is especially sensitive in the detection of small pancreatic masses which cannot be imaged with other modalities. EUS has the additional advantage of directing transduodenal fine-needle aspiration biopsies. Presently it is the most sensitive technique for the diagnosis and locoregional staging of pancreatic cancer, but limits have been identified in the lack of specificity (differentiation between malignant tumor and focal pancreatitis) and its operator-dependency. Reported is our experience with EUS in the diagnosis and staging of pancreatic cancer. Over a seven-year period 43 patients with pancreatic tumors were staged with EUS preoperatively. Twenty-two patients were submitted to surgery at our Institution and EUS findings were compared with results of pathology or surgical exploration. EUS provided sensitivity of 100% for the diagnosis of pancreatic cancer, while its accuracy for staging tumor infiltration, lymph node involvement and vascular invasion was 86.4%, 69.2% and 77.8%, respectively. Despite improvements in the noninvasive imaging modalities, endoscopic techniques are likely to remain established methods for the diagnosis and staging of pancreatic cancer. EUS with fine-needle aspiration biopsy is probably the most promising, followed by laparoscopy (and laparoscopic ultrasound) which is essential to rule out small peritoneal implants and liver metastasis.

RUOLO DELL'ENDOSCOPIA NELLA PALLIAZIONE DEL CARCINOMA PANCREATICO

The incidence of pancreatic cancer continues to increase and, although improving of diagnostic techniques, the prognosis is very poor with 5-year survival less than 5% and high mortality cancer rate. Neural and lymphatic micrometastases appear in early stages and curative resection is possible in few selected cases; in these patients there is a high local recurrence rate and a low median survival. Most patients with pancreatic cancer need palliative care of the obstructive jaundice (90%), duodenal stenosis and abdominal pain; endoscopic procedures have an important role in the treatment of these patients. Endoscopic placement of plastic biliary stents is a safe and efficient technique to perfom a biliary drainage with a short hospital stay. The use of metal stent, instead of plastic prosthesis, improve median patency of the prosthesis with a low incidence of cholangitis, but they should be used only in patients with a life expectancy of more than six months, because of their high costs. Laparoscopic gastro-entero-anastomosis is a valide alternative to laparotomic procedure in the treatment of the duodenal stenosis, with a shorter hospital stay and a lower morbidity rate. The endoscopic treatment of abdominal pain with pancreatic endoprosthesis placement or with endosonography-guided celiac plexus neurolysis is an alternative approach to radiotherapy and analgesic drugs.