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Background The aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC). Methods Patients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK. Results A total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets. Conclusion The proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.

The purpose of this study was to evaluate a single-institution experience with delivery of preoperative therapy to patients with pancreatic ductal adenocarcinoma (PDAC) prior to pancreatoduodenectomy (PD). Consecutive patients (622) with PDAC who underwent PD following chemotherapy and/or chemoradiation between 1990 and 2014 were retrospectively reviewed. Preoperative treatment regimens, clinicopathologic characteristics, operative details, and long-term outcomes in four successive time periods (1990–1999, 2000–2004, 2005–2009, 2010–2014) were evaluated and compared. The average number of patients per year who underwent PD following preoperative therapy as well as the proportion of operations performed for borderline resectable and locally advanced (BR/LA) tumors increased over time. The use of induction systemic chemotherapy, as well as postoperative adjuvant chemotherapy, also increased over time. Throughout the study period, the mean EBL decreased while R0 margin rates and vascular resection rates increased overall. Despite the increase in BR/LA resections, locoregional recurrence (LR) rates remained similar over time, and overall survival (OS) improved significantly (median 24.1, 28.1, 37.3, 43.4 months, respectively, p < 0.0001). Despite increases in case complexity, relatively low rates of LR have been maintained while significant improvements in OS have been observed. Further improvements in patient outcomes will likely require disruptive advances in systemic therapy.

Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC. Based on the “Hepatocellular Carcinoma: Eastern & Western Experiences Network,” data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox-regression analysis to construct a unique nomogram and contour plots to predict survival. The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59–0.69) and 0.61 (95 % CI, 0.56–0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size. These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction.

Gallbladder cancer (GBC) is an aggressive malignancy. Although surgical resection may be curable, most patients are diagnosed at an advanced unresectable disease stage. Cholelithiasis is the major risk factor; however the pathogenesis of the disease, from gallstone cholecystitis to cancer, is still not understood. To understand the molecular genetic underpinnings of this cancer and explore novel therapeutic targets for GBC, we examined the key genes and pathways involved in GBC using RNA sequencing. We performed gene expression analysis of 32 cases of surgically-resected GBC along with normal gallbladder tissue controls. We observed that 519 genes were differentially expressed between GBC and normal GB mucosal controls. The liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR) /RXR pathways were the top canonical pathways involved in GBC. Key genes in these pathways, including SERPINB3 and KLK1, were overexpressed in GBC, especially in female GBC patients. Additionally, ApoA1 gene expression suppressed in GBC as compared with normal control tissues. LXR and FXR genes, known to be important in lipid metabolism also function as tumor suppressors and their down regulation appears to be critical for GBC pathogenesis. LXR agonists may have therapeutic value and as potential therapeutic targets.

The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases. A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression. Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01–0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node. Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

It is not clear whether chronic hepatitis B or C virus (HBV or HCV) infection is a prognostic factor for hepatocellular carcinoma. We performed this study to determine if chronic HBV or HCV infection had any impact on postresection survival or affected patterns of failure. The records of 77 patients undergoing surgical resection for hepatocellular carcinoma between January 1990 and December 1998 were reviewed. Forty-four patients (57%) had HCV infection, 18 patients (23%) had HBV infection, and 15 patients (20%) had negative serology. There were no differences in age, sex, or tumor size among the groups, and all patients had margin-negative resections. There was a significantly higher incidence of satellitosis and vascular invasion in patients with HCV infection (32 % and 41 %, respectively; P

Hepatocellular carcinoma (HCC) that present as hemoperitoneum are uncommon, often recur as peritoneal carcinomatosis, and have poor prognosis. Systemic chemotherapies are minimally effective in advanced HCC and less so as neo-adjuvant therapy. This report describes a 47-year woman with ruptured HCC who developed recurrent carcinomatosis. She received biologically targeted systemic therapy which resulted in significant radiographic tumor response. Salvage surgery revealed complete pathologic response in all tumor nodules, thus the patient was rendered cancer-free.

Objective: Hepatocellular carcinoma (HCC) staging systems were developed using data predominantly from patients who had hepatitis and cirrhosis. Given the recent change in prevalence of viral hepatitis and cirrhosis at oncology centers, which has altered the natural history of HCC, we aimed at comparing the accuracy of HCC staging systems in patients with or without hepatitis and cirrhosis. Methods: A total of 438 patients were enrolled. Baseline clinicopathologic parameters, Barcelona Clinic Liver Cancer stage, Cancer of the Liver Italian Program score, TNM (6th edition) stage, Okuda stage, and Chinese University Prognostic Index score were prospectively obtained for all patients, and retrospectively analyzed. Kaplan-Meier analysis was used to determine overall survival (OS), Cox regression analyses were performed, and Harrell's Correspondence Index compared the staging systems' ability to predict OS duration. Subgroup analyses of patients with or without hepatitis or cirrhosis were performed. Results: Median patient OS was 13.9 months; 165 patients (37.7%) had no cirrhosis and 256 patients (58.4%) had no hepatitis. Overall, all staging systems were significantly less predictive of OS in patients who did not have cirrhosis or hepatitis. Conclusion: Our results advocate the need to further stratify HCC based on cirrhosis and hepatitis status, which may change patient risk-stratification and, ultimately, treatment decisions.

To evaluate the inguinal nodal failure rate in patients with locally advanced rectal cancer with anal canal involvement (ACI) treated with pelvic chemoradiation without elective inguinal irradiation.From 1990 and 1998, 536 patients received preoperative or postoperative chemoradiation for rectal cancer with curative intent; 186 patients had ACI (4 cm from the anal verge on rigid proctoscopy). Two patients had positive inguinal nodes at presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction) or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of 5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in only 2 patients who had documented inguinal nodal disease.The median follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative inguinal nodes at presentation developed inguinal nodal recurrence (5-year actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent successful salvage. Only 1 died of uncontrolled groin disease. Local control was achieved in both patients with inguinal nodal disease at presentation, but both died of metastatic disease. Only 3 patients with tumors4 cm from the verge developed inguinal recurrence (5-year actuarial rate1%).Inguinal nodal failure in rectal cancer patients with ACI treated with neoadjuvant or adjuvant chemoradiation is not high enough to justify routine elective groin irradiation.

Hypothesis After liver transplantation, patients with stage III hepatocellular carcinoma (HCC) experience survivals similar to those of patients with less advanced disease and of matched control subjects. Design Retrospective review of prospectively collected database. Setting University hospital. Patients Fifty-one adults with HCC and 153 matched adults without HCC who underwent orthotopic liver transplantation. Main Outcome Measures One-, 3-, and 5-year survivals for all groups. After matching for year of transplantation, age, sex, and underlying liver disease, long-term survival was compared between groups. Rates of recurrence were also measured in the HCC groups. Results From August 1, 1985, to February 28, 2002, we performed 635 adult liver transplantations, including 51 (8%) in patients with HCC. One hundred fifty-one patients without HCC who underwent transplantation were selected as controls. Patient demographic features were similar between case-control groups. The overall 5-year survival trend was worse for patients with HCC vs their matched controls (48% vs 65%;P = .07); however, this survival disadvantage was eliminated when patients with stages I through III HCC were combined and compared with their matched controls (59% vs 63%;P = .96). Survival of patients with stage III disease was comparable to that of matched controls (65% vs 59%;P = .44). Conclusions For patients with stages I through III disease, long-term survival is comparable to that of matched controls, and only patients with stage IV disease experience poorer survival. Consideration should be given to granting exception points to patients with stage III disease.

BackgroundThe biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis.MethodsBetween 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival.ResultsFifty patients with confirmed HEHE had a median follow-up of 51 months (range 1–322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9–10.7), P = 0.02].ConclusionsHEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy.