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Background Based on data from other malignancies, the number of lymph nodes evaluated and the ratio of metastatic to examined lymph nodes (LNR) may be important predictors of survival. LNR has never been investigated in a large population-based study of patients with pancreatic adenocarcinoma. Methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 4005 patients who underwent resection for pancreatic adenocarcinoma from 1988 to 2003. The effect of total lymph node count and LNR on survival was examined using univariate and multivariate analyses. Results The median number of lymph nodes examined was seven; 390 (10.1%) patients had no lymph nodes examined. Of those patients who had at least one lymph node examined, 1507 (43.3%) had no lymph node metastases (N0) and 1971 (56.7%) had metastatic nodal disease (N1). Overall median survival was 13 months, and 5-year survival was 6.8%. N1 disease was associated with a worse 5-year survival compared with N0 disease (4.3 vs 11.3%, respectively, P  < .001). Patients with N0 disease could be further stratified based on the number of lymph nodes evaluated (median survival: 1–11 nodes, 16 months vs 12 or more nodes, 23 months; P  < .001). For N1 patients, LNR was one of the most powerful factors associated with survival (LNR > 0–0.2, 15 months; LNR > 0.2–0.4, 12 months; LNR > 0.4, 10 months) ( P  < .001). Conclusions Most patients have an inadequate number of lymph nodes evaluated following pancreatic surgery. N0 patients who have fewer than 12 lymph nodes examined may be understaged. In patients with N1 disease, LNR may better substratify patients with regard to prognosis.

Background Macroscopic vascular invasion is known to be a poor prognostic factor in hepatocellular carcinoma (HCC). The aim of this study was to determine the outcomes and predictive factors after hepatic resection for HCC with microvascular invasion (MVI). Methods One hundred ten patients who underwent curative resection for HCC without macroscopic vascular invasion were included in this retrospective study. The risk factors of these patients for recurrence-free and disease-specific survival were investigated, and the clinicopathological factors predicting the presence of MVI were also determined. Results Of the 110 resected specimens, 49 (45%) had evidence of MVI. By univariate analysis, MVI was found to be statistically significantly associated with greater tumor size, gross classification, histological grade, and intrahepatic micrometastasis. Gross classification proved to be the only independent predictive factor for MVI by multiple logistic regression analysis. By multivariate analysis, cirrhosis and MVI were identified as independent risk factors for recurrence-free survival. The 5-year recurrence-free survival rates for patients with and without MVI were 20.8% and 52.6%, respectively. By multivariate analysis, the number of tumors, presence of MVI, and intrahepatic micrometastasis were identified as independent predictors of disease-specific survival. The 5-year disease-specific survival rates for patients with and without MVI were 59.3% and 92.0%, respectively. Conclusions The presence of MVI was the most important risk factor affecting recurrence and survival in HCC patients after curative resection. Furthermore, this study showed that gross classification of HCC can be very helpful in predicting the presence of MVI.

Background Pancreas is a possible site of metastases from renal cell carcinoma (RCC). The aim of this study was to define the role of surgery in their treatment. Methods We retrospectively analyzed 36 patients with pancreatic metastasis from RCC observed between January 1998 and February 2006. Patients were categorized into three risk groups according to the modified Memorial Sloan-Kettering prognostic factors model. Results Resective surgery was performed in 23 patients, as follows: 11 distal pancreatectomy, 5 enucleation, 4 pancreatoduodenectomy, 2 total pancreatectomy, and 1 middle pancreatectomy. No perioperative mortality was observed; the morbidity rate was 47.8%. All patients who underwent resection belonged to the favorable risk group. Surgical resection was excluded in 13 cases because of locally advanced disease (2 cases) or extrapancreatic disease (11 cases); 5 of these patients were at favorable, 7 at intermediate, and 1 at poor risk. In patients undergoing surgery, the 5-year actuarial survival rate was 88%, and median disease-free survival was 44 months. Patients who did not undergo surgery had a 5-year survival rate of 47%, with a median survival time of 27 months ( P  = .02). Conclusions Patients with pancreatic metastases from RCC belonging to a favorable risk group are candidates for resection, even in the presence of another metastatic site or multifocal pancreatic disease.

Background Orthotopic liver transplantation (OLT) is the best available option for early hepatocellular carcinoma (HCC), although its application is limited by stringent selection criteria, costs, and deceased donor graft shortage, particularly in Asia, where living donor liver transplant (LDLT) has been developed. Methods This article reviews the present standards for patient selection represented by size-and-number criteria with particular references to Milan Criteria and novel prediction models based on results achieved in patients exceeding those limits, with consideration of the expanded indication represented by the UCSF Criteria. Results The expected outcomes after deceased donor liver transplant (DDLT) or LDLT are favorable if predetermined selection criteria are applied. However, selection bias, difference in waiting time, and ischemia-regeneration injuries of the graft among DDLT vs LDLT may influence long-term results. In the article, the differences between East and West in first-line treatments for HCC (resection vs transplantation), indications, and ethics for the donor, are summarized as well as possible novel predictors of tumor biology (especially DNA mutation and fractional allelic loss, FAI) to be considered for better outcome prediction. Conclusions Liver transplantation remains the most promising product of modern surgery and represents a cornerstone in the management of patients with HCC.

Background Staging laparoscopy for patients with radiographically resectable pancreatic adenocarcinoma has been reported to yield an 8–15% finding of unresectable disease. Factors associated with the likelihood of subradiographic unresectable disease have not been clearly defined. Methods A prospectively maintained pancreatic database was reviewed and patients were identified who underwent staging laparoscopy for radiographically resectable pancreatic adenocarcinoma between January 2000 and December 2006. Preoperative carbohydrate antigen 19-9 (CA 19-9) values were assessed for their association with the presence of subradiographic unresectable disease. Results Four hundred ninety-one patients underwent staging laparoscopy. Resection was performed in 80% ( n  = 395). Of the 96 patients with unresectable disease, 75 (78%) had metastases either in the liver ( n  = 60) or peritoneum ( n  = 15). Preoperative CA 19-9 values were available for 262 of the 491 patients. Fifty-one of these patients had unresectable disease, of which 78% were due to distant disease. The median preoperative CA 19-9 value for patients who underwent resection was 131 U/ml versus 379 U/ml for those patients with unresectable disease ( P  = 0.003). A receiver operating characteristics (ROC) curve was developed for preoperative CA 19-9 value and tumor resectability. The statistically optimal cutoff value was determined to be 130 U/ml. Unresectable disease was identified in 38 of the 144 patients (26.4%) with a preoperative CA 19-9 ≥ 130 U/ml, and in 13 of the 118 patients (11%) with a CA 19-9 < 130 U/ml ( P  = 0.003). CA 19-9 values greater than 130 U/ml remained a predictor of tumor unresectability on multivariate regression analysis [hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.34–5.44; P  = 0.005]. Conclusion In this study, preoperative CA 19-9 values were strongly associated with the identification of subradiographic unresectable disease. Preoperative CA 19-9 values may allow surgeons to better select patients for staging laparoscopy.

Hepatocellular carcinoma (HCC) is a common cancer in the world due to high prevalence of hepatitis B or C virus infection. Research in recent years has uncovered important molecular pathways involved in development and progression of HCC. Several genetic aberrations and molecular mechanisms responsible for initiation of hepatocarcinogenesis have been identified. Novel biomarkers for HCC are being developed for better detection and prognostication. Alpha-fetoprotein, the conventional marker of HCC, has limited sensitivity and specificity. Serum levels of isoforms of AFP based on differential lectin binding of the glycan moiety appear to be more sensitive and specific than total AFP level in early detection of HCC. The clinical usefulness of other HCC biomarkers such as des-γ-carboxy prothrombin and glypican-3 are under investigation. HCC is an aggressive tumor with early vascular invasion and metastasis. Studies over the past two decades have elucidated the clinical predictors of outcome, leading to several staging systems for HCC based on clinical parameters. However, the predictive accuracy of clinical staging systems is limited. Recent studies suggested that biological factors may provide additional prognostic information. In particular, gene expression profiling appears to be a promising approach. Study of tumor angiogenesis in HCC reveals that the expression of angiogenic factors such as vascular endothelial growth factor and angiopoietins may also predict prognosis. The elucidation of tumor biology of HCC is of particular importance in the current era of rapid development of anti-cancer molecular targeting agents, which provide hope for an effective systemic therapy for HCC.

Background Cholangiocarcinoma (CCA) is associated with poor survival and therapeutic nihilism. To date, there has not been an examination of the surgical management of CCA at a population level. Methods Using the Surveillance, Epidemiology and End Results (SEER) database, we identified all patients with intrahepatic CCA diagnosed between 1988 and 2003. Tumors categorized as a single, unilobar lesion with no evidence of vascular invasion were defined as localized. It was then determined whether patients received cancer directed surgery (CDS). Multivariable logistic regression was used to evaluate factors associated with CDS in patients with localized disease. The influence of CDS on overall survival (OS) was evaluated using Kaplan–Meier curves and Cox proportional hazards modeling. Results Only 446 (12%) of 3,756 patients with intrahepatic CCA underwent CDS. On multivariable analysis, non-Klatskin tumor ( p < 0.01) and younger age ( p = 0.02) was associated with CDS. Localized disease was strongly associated with CDS ( p < 0.01); however, only 91 (37%) of these 248 patients underwent CDS. Of patients with localized disease, those who had CDS had significantly better survival than those who did not ( p < 0.01), with median overall survival (OS) of 44 months versus 8 months, and five-year OS of 42% versus 4%, respectively. Conclusions Patients with localized CCA who are selected for CDS are strongly associated with improved survival, with rates approaching that found in single institution studies. However, many patients with localized tumors do not receive potentially curative cancer-directed surgery. Further study is warranted to address the barriers to the delivery of appropriate care to these patients.

Background The best measure of the technical success of radiofrequency ablation (RFA) is local recurrence (LR). The aim of this prospective study is to identify factors that predict LR. Methods Three hundred thirty-five patients with 1032 unresectable liver tumors underwent laparoscopic RFA between November 1999 and August 2005. All lesions were assessed prospectively regarding tumor type, size, liver segment, blood vessel proximity, and central or peripheral location in the operating room and size of ablation zone at 1-week computed tomographic (CT) scans. Lesions that recurred in follow-up CT scans were identified prospectively. LR was categorized as contiguous or adjacent. Univariate Kaplan-Meier and Cox proportional hazard models were used for statistical analysis. Results LR was identified 21.7% of tumors on CT scans with a mean follow-up of 17 months (median, 12 months; range, 3–68 months). This was contiguous in 70% and adjacent in 30%. LR rate per tumor was highest for colorectal metastasis (34%), followed by noncolorectal, nonneuroendocrine metastasis (22%), hepatocellular carcinoma (18%), and neuroendocrine metastasis (6%). By univariate analysis, tumor type and size, ablation margin, liver segmental location, blood vessel proximity, and type of ablation (first time vs. repeat) were found to affect LR. The Cox proportional hazard model identified tumor type, tumor size, ablation margin, and blood vessel proximity to be independent predictors of LR. Conclusion LR after RFA is predicted by certain tumor characteristics and technical factors. This information can be used intraoperatively to identify those tumors at a higher risk for failure.

Background The role of fusion positron emission tomography/computed tomography scans (PET/CT) in staging of patients with pancreatic neoplasms (PN) is poorly defined. PET/CT may serve as an adjunct to standard imaging by increasing occult metastases detection. The purpose of this study was to assess the additional value, in relation to computed tomography (CT), of PET/CT imaging for patients with PN. Methods Eighty-two patients with potentially resectable PN underwent staging with PET/CT and CT of the chest and abdomen. Sensitivity of diagnosing pancreatic cancer by PET/CT avidity was evaluated. The sensitivity of detecting metastases was compared between PET/CT, standard CT, and the combination of PET/CT and CT. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. Results The sensitivity and specificity of PET/CT in diagnosing pancreatic cancer were 89% and 88%, respectively. Sensitivity of detecting metastatic disease for PET/CT alone, standard CT alone, and the combination of PET/CT and CT were 61%, 57%, and 87%, respectively. Findings on PET/CT influenced the clinical management in seven patients (11%), two with a supraclavicular lymph node (LN), two occult liver lesions, two peritoneal implants, and one peri-esophageal LN. Conclusion This study evaluated PET/CT in the initial work-up of patients with PN. PET/CT increased sensitivity (87%) for detection of metastatic disease when combined with standard CT. In invasive cancer, PET/CT changed the management in 11% of our patients. PET/CT should be considered in the initial work-up of patients with potentially resectable pancreatic lesions.

Background Absence of major arterial tumor involvement has generally been regarded as a major criterion for resectability of pancreatic tumors. We hypothesize that resection of a tumor-involved hepatic artery (HA) or celiac artery (CA) with reconstruction may offer a survival benefit to patients whose tumors were traditionally regarded as unresectable. Methods All patients with pancreatic adenocarcinoma treated between 1996 and 2007 were reviewed. Patients were included if they underwent resection of the HA or CA during pancreatectomy. Survival was analyzed by Kaplan-Meier survivor functions, Cox proportional hazard models, and the log rank test. Results Twelve patients (six men and six women) with adenocarcinoma underwent pancreatectomy with resection of a tumor-involved HA (n = 2) and/or CA (n = 10). Median age at diagnosis was 62 years (range, 53–73 years). All patients completed neoadjuvant chemoradiotherapy with or without full dose chemotherapy before resection. Procedures performed were six extended pancreaticoduodenectomies, two proximal subtotal pancreatectomies, two distal pancreatectomies, and two total pancreatectomies. Ten cases involved celiac resections, and two had isolated HA resections. The 60-day mortality was 17% (2 of 12). Median survival after diagnosis was 20 months (range, 6–41 months). Median survival after resection was 17 months (range, 1–36 months). Survival was not statistically significantly related to age, sex, margin status, or preoperative CA19-9 level. The 3-year survival was 17%. There were no 5-year survivors. Conclusions Resection of the HA or CA with reconstruction may prolong survival for selected patients who undergo pancreatic resection after neoadjuvant therapy. However, this aggressive approach did not result in any long-term survivors in our series.