Management of Hepatocellular Adenoma: Recent Advances.

Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the ß-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended.

Distinguishing autoimmune pancreatitis from pancreaticobiliary cancers: current strategy.

OBJECTIVE: A review of the literature to identify current modalities for the diagnosis of autoimmune pancreatitis (AIP) with the objective of establishing a strategy to distinguish it from pancreaticobiliary cancers. BACKGROUND: Pancreatic and biliary manifestations of AIP mimic pancreaticobiliary cancers. Misdiagnosis of AIP can result in major surgery for a steroid-responsive disease. METHODS: A review of the literature was performed to identify recent advances in the diagnosis of AIP and evaluate outcomes with various diagnostic strategies to minimize operative intervention for an autoimmune disease. RESULTS: Diagnostic criteria for AIP are based on histology, imaging, serology, extrapancreatic organ involvement, and response to steroid therapy. The most commonly involved extrapancreatic sites are bile duct, kidney, and retroperitoneum. The Mayo Clinic diagnostic strategy utilizes core biopsy of the pancreas and the Japanese strategy depends on a characteristic pancreatogram. The rate of operative intervention was similar with both strategies and none of the patients with cancer received steroid therapy. Immunoglobulin G subtype 4 (IgG4)-associated cholangitis mimics cholangiocarcinoma and presence of more than 10 IgG4-positive plasma cells/high power field on endoscopic biopsy of the bile duct was diagnostic for AIP in 88% patients. Biliary complications and early relapse are common after surgical resection and immunomodulatory drugs can maintain long-term remission. CONCLUSION: Criteria based on histology, imaging, endoscopy, serology, extrapancreatic organ involvement, and response to steroid therapy improve the diagnostic yield for AIP. Application of diagnostic and therapeutic protocols by a multidisciplinary team will optimize outcomes with a decline in the rate of operative intervention for AIP, a steroid-responsive disease with propensity for relapse.

Oncologic resection for malignant tumors of the liver.

OBJECTIVE: An evidence-based review to ascertain the operative strategy for oncologic resection of malignant tumors of the liver and an optimal postoperative outcome. BACKGROUND: Recommendations for resection of malignant tumors of the liver based on traditional considerations of locoregional control and survival benefit are modified by the functional reserve of the liver remnant. METHODS: Recent publications including prospective randomized trials reporting outcomes with various surgical approaches were reviewed to establish the best current practices. RESULTS: The goal of hepatectomy for primary or metastatic tumors of the liver is complete resection with evidence that an anatomic resection in hepatocellular carcinoma and hilar cholangiocarcinoma improves survival. For nonanatomic resections the optimal width of the resection margin varies with the pathological type of tumor. Anterior approach to major hepatectomy is a "no-touch" technique that minimizes manipulation of the tumor-bearing liver. Vascular invasion is associated with dismal prognosis and limited major vascular resection is indicated to achieve an R0 (no residual disease) resection for prolongation of survival. Concomitant regional lymphadenectomy is of prognostic value, however it is not performed routinely because its therapeutic value remains unproven. Perioperative blood transfusion and postoperative morbidity are independent predictors of survival emphasizing the importance of measures such as portal vein embolization, hepatic pedicle clamping and preservation of venous drainage of the liver remnant. CONCLUSION: The operative strategy for resection of malignant tumors of the liver should address the key components of the extent of hepatectomy including anatomic resection and optimal pathologic margins, use of the anterior approach, necessity for vascular resection, regional lymphadenectomy and measures to minimize blood loss and postoperative morbidity for maximal survival benefit.

Metabolic syndrome and hepatic resection: improving outcome.

OBJECTIVE: A review of the peri-operative risk associated with hepatic resection in patients with metabolic syndrome (MetS) and identification of measures for the improvement of cardiometabolic disturbances and liver-related mortality. BACKGROUND: MetS and its hepatic manifestation non-alcoholic fatty liver disease (NAFLD) are associated with an increased operative mortality in spite of a significant improvement in peri-operative outcome after hepatic resection. METHODS: A review of the English literature on MetS, liver resection and steatosis was performed from 1980 to 2011 using the MEDLINE and PubMed databases. RESULTS: MetS is a predictor of NAFLD and patients with multiple metabolic risk factors may harbour non-alcoholic steatohepatitis (NASH) predictive of operative and cardiovascular mortality. Pre-operative diagnosis of unsuspected NASH with the selective use of a liver biopsy can modify the operative strategy by limiting the extent of hepatic resection, avoiding or altering the pre-operative chemotherapy regimen and the utilization of portal vein embolization. Thiazolidinediones are therapeutic for MetS and NASH and Vitamin E for active NASH; however, their utility in improving the peri-operative outcome after hepatic resection is unknown. A short-term regimen for weight loss improves post-operative patient and liver-related outcomes in patients with >30% steatosis. Cardiovascular disease associated with MetS or NAFLD should be managed aggressively. Peri-operative measures to minimize thrombotic events and acute renal injury secondary to the pro-inflammatory, prothrombotic state of MetS may further improve the outcome. CONCLUSION: Potential candidates for hepatic resection should be screened for MetS as the pre-operative identification of NASH, short-term treatment of significant steatosis, cardiovascular risk assessment and optimization of each component of MetS may improve the peri-operative outcome in this high-risk subset of patients.

CD24 expression is an independent prognostic marker in cholangiocarcinoma.

CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p=0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p=0.08). On multivariate analysis, the use of chemotherapy (p=0.0014, hazard ratio 0.069) and the CD24 overexpression (p=0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy.

Potential prognostic biomarkers in pancreatic juice of resectable pancreatic ductal adenocarcinoma.

Despite potentially curative surgery pancreatic cancer has a dismal prognosis. Serum cancer antigen 19-9 (CA 19-9) correlates with tumor burden, resectability and survival in patients with pancreatic ductal adenocarcinoma. Identification of novel biomarkers may facilitate early diagnosis of pancreatic cancer and improve survival. Pancreatic juice is a rich source of cancer-specific proteins rendering it a promising tool for identifying biomarkers. Recent proteomic and microRNA expression analyses have identified several biomarkers of potential diagnostic and prognostic value. Tumor markers CA 19-9 and carcinoembryonic antigen (CEA) are widely used in the characterization of premalignant and malignant lesions of the pancreas. Elevated level of CEA in bile is a marker for malignancy and a predictor of hepatic recurrence. The potential value of CA 19-9, CEA and lactate dehydrogenase as prognostic biomarkers in pancreatic juice and bile is unknown. Specimens of pancreatic juice and bile can be readily collected during surgical resection of the tumor. Profiling of pancreatic juice and bile to identify novel prognostic biomarkers may improve selection of patients for adjuvant therapy with a favorable impact on overall survival in patients diagnosed with pancreatic cancer.

Simultaneous Courvoisier's and double duct signs.

Presence of Courvoisier's or double duct signs in a jaundiced patient is suggestive of malignant obstruction of the pancreaticobiliary ductal system. The oncologic impact of the simultaneous occurrence of these signs on the survival of patients with periampullary cancer is unknown. We report a case of obstructive jaundice secondary to an ampullary cancer demonstrating the Courvoisier's sign on clinical examination and a double duct sign on imaging. The patient underwent a pancreaticoduodenectomy which confirmed an ampullary adenocarcinoma.

Eosinophilic ascites: A diagnostic and therapeutic challenge.

Eosinophilic gastroenteritis (EGE) is a rare condition characterized by eosinophilic infiltration of the gastrointestinal tract. Depending on the dominant layer of infiltration it is classified into three types namely, mucosal, muscularis and subserosal. The most uncommon variant is the subserosal type characterized by primarily subserosal disease, eosinophilic ascites and peripheral hypereosinophilia. The clinical features are non-specific with history of atopic predisposition and allergy. Endoscopic biopsy is frequently non-diagnostic due to an uninvolved gastrointestinal mucosa rendering its diagnosis a challenge. The mainstay of diagnosis is peripheral hypereosinophilia and eosinophil-rich ascitic fluid on diagnostic paracentesis. Oral steroid therapy is usually the first line of treatment with dramatic response. Due to a propensity for relapse, steroid-sparing therapy should be considered for relapses of EGE. We report a case of subserosal EGE with diagnostic clinical features and treatment response and review the current strategy in the management of eosinophilic ascites.

Richter's hernia.

Richter's hernia is associated with rapid onset of gangrene and a high mortality. We report a case of a strangulated inguinal Richter's hernia of the cecum requiring a laparotomy and bowel resection. Due to the misleading clinical presentation, a high index of suspicion, particularly in patients with a history of laparoscopic surgery, will minimize delay in diagnosis.

Extraskeletal osteosarcoma: a case report and review of the literature.

We report an instructive case of extraskeletal osteosarcoma in a 63-year-old African American male who presented after an episode of recent trauma, with clinical and radiological features characteristic of this neoplasm. Osteosarcoma is the most common primary malignant tumor of bone in young adults, but the extraskeletal variety is very uncommon. The radiological and pathological features of this neoplasm will be discussed, along with a review of the literature.

Hemorrhagic liver cyst.

INTRODUCTION: Simple cysts of the liver are usually discovered incidentally on abdominal imaging, and asymptomatic simple cysts do not require treatment regardless of size. DISCUSSION: We report a case of a symptomatic simple cyst of the liver complicated by intracystic hemorrhage for which a partial hepatectomy was performed. Treatment of simple hepatic cysts is indicated in the presence of associated symptoms or complications, and inability to exclude a cystic neoplasm requires operative intervention.

The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma.

BACKGROUND: The objective of this study was to evaluate the impact of adjuvant radiation therapy (RT) on regional recurrence and survival after therapeutic lymphadenectomy (TL) for clinically advanced, lymph node-metastatic melanoma. METHODS: Six hundred fifteen patients who had clinically advanced, regional lymph node-metastatic disease underwent TL. All patients were appropriate potential candidates for adjuvant RT (enlarged or multiple positive lymph nodes, extracapsular extension) because of a high risk for regional recurrence regardless of whether or not they received RT. Patient-related, tumor-related, and treatment-related variables that were associated with recurrence, survival, and treatment-related morbidity with and without RT were analyzed. RESULTS: The median follow-up was 5 years. The actuarial 5-year regional lymph node basin control rate was 81%. On multivariate analysis, the number of positive lymph nodes, the number of lymph nodes removed, and the use of adjuvant RT were associated with improved regional control. Treatment-related morbidity, particularly lymphedema, was increased with the use of adjuvant RT and an inguinal site of lymph node metastases. At last follow-up, 268 patients were alive with actuarial 5-year distant metastasis-free survival (DMFS) and disease-specific survival (DSS) rates of 40% and 48%, respectively. On multivariate analysis, DMFS and DSS both were influenced by the number of positive lymph nodes and the number of lymph nodes removed. In addition, DSS was influenced by primary tumor thickness and the receipt of adjuvant RT. CONCLUSIONS: Adjuvant RT was associated with improved regional lymph node basin control compared with TL alone in patients with high-risk, clinically advanced, lymph node-metastatic melanoma. Although it is a regional therapy, adjuvant RT also may have an impact on DSS.

Surgical management and outcome in primary adenocarcinoma of the small bowel.

BACKGROUND: Primary adenocarcinoma of the small bowel is a rare malignancy and is associated with poor survival outcome. Patient, tumor and treatment-related factors were analyzed for their association with recurrence and survival. METHODS: Between 1971 and 2005, 64 patients with primary adenocarcinoma of the small bowel were treated at our institution. Clinico-pathologic data, operative details, postoperative treatment, recurrence pattern and survival were reviewed. RESULTS: The most common clinical features at presentation included abdominal pain (n = 33; 51.6%) or bowel obstruction (n = 20; 31.3%). The most frequently involved portion of the small bowel was the duodenum (n = 41; 64%). A segmental bowel resection was performed in 30 patients and pancreaticoduodenectomy in 14 patients. Postoperative mortality and morbidity rates were 3.6% (n = 2) and 14.5% (n = 8), respectively. Of the 55 patients who underwent operative intervention, a curative resection was performed in 30 (54.5%). The most common sites of recurrence following a curative resection were the liver and lung. Median survival for all 64 patients was 18 months with a 5-year survival of 21.1%. On multivariate analysis, absence of distant metastatic disease (5-year survival 30.4%), curative resection (5-year survival 44.8%) and pathological T stage 1-3 (5-year survival 39.2%) were identified as independent predictors of survival. CONCLUSIONS: A curative resection in the absence of both distant metastases and pathological T4 tumor provides the best survival outcome. Recurrence at distant sites is the predominant pattern of failure following a curative resection, suggesting a role for adjuvant therapy.

Role of TAP-1 and/or TAP-2 antigen presentation defects in tumorigenicity of mouse melanoma.

Mutations in transporters associated with antigen processing (TAP-1 and -2) required for the transport of cytosolic endogenous peptides to the endoplasmic reticulum correlate with increased metastatic potential and reduced host survival in several malignancies. To address the possible function of TAP as a "tumor suppressor" gene, we show that correction of TAP-1 and/or TAP-2 defects in B16 mouse melanoma enhanced the cell surface expression of MHC class I molecules and significantly reduced the rate of subcutaneous tumor growth and pulmonary metastatic burden. Cytotoxic assays confirmed increased sensitivity of TAP-1 and/or TAP-2 transfected clones of B16 melanoma to cytotoxic T lymphocytes. These results indicate that the expression of TAP limits the malignant potential of tumors with implications for CD8(+) T cell-based immunotherapy in controlling growth of certain TAP-deficient malignancies.