Primary Hepatobiliary Malignancies Research Articles

PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.

Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA.

Open vs robotic hepatectomy for primary hepatobiliary malignancy: validated outcomes and survival analysis

Open vs robotic hepatectomy for primary hepatobiliary malignancy: validated outcomes and survival analysis

Role of 68 Ga-FAPI PET/CT in Assessing Hepatobiliary Malignancies : A Prospective Pilot Study.

Preliminary studies showed good expression of fibroblast activating protein inhibitor (FAPI) in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Our aims were to study the diagnostic performance of 68 Ga-FAPI PET/CT in diagnosing the primary hepatobiliary malignancies and to compare its performance with 18 F-FDG PET/CT. Patients suspected to have HCC and CC were recruited prospectively. FDG and FAPI PET/CT studies were completed within 1 week. Final diagnosis of malignancy was achieved by tissue diagnosis (either histopathological examination or fine-needle aspiration cytology) and radiological correlation from conventional modalities. Results were compared with final diagnosis and expressed as sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Forty-one patients were included. Thirty-one were positive for malignancy and 10 were negative. Fifteen were metastatic. Of 31, 18 were CC and 6 were HCC. For overall diagnosis of the primary disease, FAPI PET/CT performed exceptionally compared with FDG PET/CT with sensitivity, specificity, and accuracy of 96.77%, 90%, and 95.12%, respectively, versus 51.61%, 100%, and 63.41% for FDG PET/CT. FAPI PET/CT clearly outperformed FDG PET/CT for the evaluation of CC with sensitivity, specificity, and accuracy of 94.4%, 100%, and 95.24%, respectively, whereas for FDG PET/CT sensitivity, specificity, and accuracy were 50%, 100%, and 57.14%, respectively. Diagnostic accuracy of FAPI PET/CT was 61.54% for metastatic HCC compared with 84.62% for FDG PET/CT. Our study highlights the potential role of FAPI-PET/CT in evaluating CC. It also ascertains its usefulness in the cases of mucinous adenocarcinoma. Although it showed a higher lesion detection rate than FDG in primary HCC, its diagnostic performance in the metastatic setting is questionable.

Effect of preoperative liver-directed therapy prior to hepatic resection

IntroductionHepatobiliary malignancies present with advanced disease precluding upfront resection. Liver-directed therapy (LDT), particularly Y-90 radioembolization and transarterial chemoembolization (TACE), has become increasingly utilized to facilitate attempt at oncologic resection. However, the safety profile of preoperative LDT is limited. MethodsRetrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2014–2016. Primary objective was evaluation of outcomes between preoperative LDT cases and those that received upfront resection. ResultsA total of 8923 cases met selection criteria. 192 cases (2.15%) received either Y-90 or TACE prior to hepatectomy. Multivariate analysis for all study patients revealed preoperative LDT significantly increased the risk of perioperative transfusion (OR 2.19, 95% CI 1.445–3.328, P < 0.0001), sepsis (OR 2.21, 95% CI 1.104–4.411, P = 0.022), and liver failure (OR 2.72, 95% CI 1.562–4.747, P < 0.0001). Subgroup analysis found for primary hepatobiliary malignancies LDT only increased the risk for liver failure. While for secondary hepatic tumors LDT significantly increased perioperative transfusion, sepsis, cardiac failure, renal failure, liver failure, and mortality. The complication profile also significantly increased with advanced T stage. Conversely, on propensity score matching preoperative LDT did not significantly increase perioperative complications. ConclusionPreoperative LDT has the potential to convert inoperable hepatic tumors into resectable disease but there is a general increased risk for significant postoperative complications, most notable liver failure. However, on controlled analysis preoperative LDT does not increase perioperative complications and should not be considered a contraindication to resection.

Genetic profile and survival outcomes in a modern cohort of patients with biliary tract cancers (BTC): Single center experience in New York City.

e16157 Background: BTCs are the second most common primary hepatobiliary malignancy with rising incidence and mortality worldwide. Individual characterization of BTCs at a genomic level is critical to tailor management strategies. Currently available data stem from studies in predominantly White populations. We conducted a retrospective study to determine the demographic, clinical and survival profiles of patients with BTCs seen in our center, who had been tested for genomic alterations. Methods: We identified 69 patients with BTCs diagnosed between 2015-2022 who had tissue-based genomic results available. Chi-square test was used to compare frequency distributions. Univariate analysis with cox regression model and multivariate cox proportional hazards test were conducted. Kaplan-Meier curves were used to assess overall survival (OS). Results: Median age at diagnosis was 67 years and median follow-up time was 15.5 months. Racial and ethnic minority populations were highly represented with 41% Hispanic, 29% Black and 17% White patients. ECOG performance status (PS) ranged between 0-2 at diagnosis. Most patients (40%) had stage IV BTC, with intrahepatic cholangiocarcinoma (CCA) being most prevalent (48%). On univariate modeling, variables associated with a shorter OS were age (HR 1.03, 95% CI 1.00-1.07, p = 0.05) and ECOG PS of 2 (HR 7.03, 95% CI 1.49-33.3, p = 0.014). In a multivariate model, ECOG PS 2 was independently associated with a shorter OS. The most common mutations (N, %) found on NGS were TP53 (28, 41%), KRAS (13, 19%), ARID1A (11, 16%), PIK3CA (9, 13%), ERBB2 (5, 7%) and FGFR2 (5, 7%). Median tumor mutation burden (TMB) was 4 Mut/Mb, with 18.9% having hypermutated (≥10 Mut/Mb) BTCs. Potentially actionable targets were found in 40 (58%) patients, 5.8% of which received targeted therapies with a median OS of 27 months (median OS of entire cohort was 22.8 months). KRAS mutation was significantly less common in intrahepatic CCA compared to the other BTC subtypes (p = 0.016). Race or ethnicity were not found to have a significant association with mutation frequency (Table). TP53 and ARID1A mutations were associated with a trend towards reduced OS in univariable analysis, with HR = 1.46 (p = 0.29) and HR = 1.64 (p = 0.28) respectively. Conclusions: Extensive genomic diversity was observed among BTC patients in our center which serves a large minority population. Studies with larger sample size are required to expand our understanding of the genomic spectrum in BTCs, its therapeutic and survival implications. [Table: see text]

Imaging mimickers of cholangiocarcinoma: a pictorial review.

Cholangiocarcinoma (CCA) is the second most common primary hepatobiliary malignancy and presents as three separate morphological subtypes; namely mass-forming, periductal-infiltrating, and intraductal-growing patterns. Each of these subtypes have distinct imaging characteristics, as well as a variety of benign and malignant mimics, making accurate diagnosis of CCA on imaging challenging. Whilst histopathological examination is required to arrive at a definitive diagnosis, it is still important for radiologists to be cognizant of these entities and provide reasonable differential diagnoses, as these potentially have a large impact on patient management. This pictorial essay illustrates the three morphological subtypes of CCA, as well as some important mimics for each subtype, that are encountered in clinical practice.

S1524 Cholangiocarcinoma in IBD Without PSC

Introduction: Cholangiocarcinoma (CCA) is an uncommon cancer of the biliary tree that occurs at increased incidence in certain chronic liver diseases including Primary Sclerosing Cholangitis (PSC). Patients with PSC have markedly increased rates of Inflammatory Bowel Disease (IBD), but having IBD alone is also considered a risk factor for CCA. This is a unique presentation of CCA in a patient with Crohn’s Disease (CD) in deep remission. At the time of presentation, he was also noted to have decompensated cirrhosis attributed to non-alcoholic fatty liver disease (NAFLD). Case Description/Methods: A 57-year-old male with CD in remission on infliximab presented with new stigmata of cirrhosis. On MRI imaging, he was found to have a liver mass concerning for a primary hepatobiliary malignancy within a cirrhotic appearing liver without findings suggestive of PSC. Evaluation from years prior was notable for a negative serologic work-up for a chronic intermittent mild elevation of his transaminases with clinical notes suggesting the elevation was due to NAFLD. Tumor markers were notable for carbohydrate antigen 19-9 (CA19-9) 32 U/mL, a carcinoembryonic antigen (CEA) 5.5 ng/mL, and an alpha-1-fetoprotein (AFP) of 174 ng/mL. Biopsy of the liver mass demonstrated poorly differentiated adenocarcinoma with specialty stains suggesting CCA. He was started on palliative chemotherapy and targeted therapy with olaparib. Discussion: CCA is a highly fatal tumor and is the second most common primary hepatic malignancy. Risk factors include IBD, hepatitis B and C viruses, cirrhosis, diabetes mellitus, obesity, alcohol consumption, tobacco smoking, and parasitic infection. PSC is the main risk factor in the United States. Postulated mechanisms of carcinogenesis include chronic inflammation, proliferation of biliary epithelium, production of endogenous bile mutagens, and bile stasis. Interestingly this patient did not have PSC although he did have cirrhosis and IBD. He also had an elevated AFP which suggested a diagnosis of Hepatocellular Carcinoma (HCC). Liver biopsy was performed to clarify the diagnosis as imaging was atypical for HCC. This case demonstrates a unique presentation of CCA in the background of quiescent CD and undiagnosed cirrhosis and highlights the limitations of imaging and the currently available tumor markers for hepatobiliary malignancies.

Diagnosis and staging of hepatobiliary malignancies: Potential incremental value of (18)F-FDG-PET/MRI compared to MRI of the liver.

The purpose of the study was to investigate the potential added value of 18F-FDG-PET/MRI (functional information derived from PET) over standard diagnostic liver MRI (excellent soft tissue characterization) in diagnosing and staging suspected primary hepatobiliary malignancies including extrahepatic cholangiocarcinoma (ECC), intrahepatic cholangiocellular carcinoma (ICC) and gallbladder cancer (GBCA). Twenty consecutive patients with suspected hepatobiliary malignancy were included in this retrospective study. All patients underwent combined whole-body (WB) 18F-FDG-PET/MRI including contrast-enhanced MRI of the liver, contrast-enhanced WB-MRI and WB 18F-FDG-PET. Two experienced readers staged hepatobiliary disease using TNM criteria: first based on MRI alone and then based on combined 18F-FDG-PET/MRI. Subsequently, the impact of FDG-PET/MRI on clinical management compared to MRI alone was recorded. Histopathologic proof served as the reference standard. Hepatobiliary neoplasms were present in 16/20patients (ECC n = 3, ICC n = 8, GBCA n = 5), two patients revealed benign disease, two were excluded. TNM staging with 18F-FDG-PET/MRI was identical to MRI alone in 11/18 (61.1 %) patients and correctly changed the stage in 4/18 (22.2 %), resulting in a change in management for 2/4 patients (11.1 %). 18F-FDG-PET/MRI was false-positive in 3/18 cases (16.7 %). Both MRI and 18F-FDG-PET/MRI were falsely positive in 1 case without malignancy. A small incremental benefit of 18F-FDG-PET/MRI over standard MRI of the liver was observed. However, in some cases 18F-FDG-PET/MRI may lead to false-positive findings. Overall there is seemingly limited role of 18F-FDG-PET/MRI in patients with suspected hepatobiliary malignancy.

Down-regulation of USP8 Inhibits Cholangiocarcinoma Cell Proliferation and Invasion.

ObjectiveCholangiocarcinoma is the second most common primary hepatobiliary malignancy with high incidence and recurrence rate. Ubiquitin-specific protease 8 (USP8) is recently reported to be involved in tumor progression. Herein, we aimed to investigate the effects of USP8 on the growth and metastasis abilities of cholangiocarcinoma cells.MethodsThe siRNA interference was used to knock down USP8 in cholangiocarcinoma cell lines QBC939 and RBE; Hucct-1 cells were transfected with pcDNA3.1-USP8 to up-regulate its expression. The effects of USP8 on cholangiocarcinoma were detected by cell function assays. We analyzed the expressions of USP8, Bcl2, Bax, cleaved caspase-3, cleaved caspase-9, Akt, p-Akt, Cyclin D1 and P70S6K by Western blot analysis.ResultsWe demonstrated that knockdown of USP8 significantly inhibited the proliferation, migration and invasion of QBC939 and RBE cells in vitro, while USP8 overexpression showed significant promoting effects on Hucct-1 cells. Moreover, silencing of USP8 also promoted apoptosis in cholangiocarcinoma cells by regulating the Bcl-2/Bax axis and Caspase cascade; up-regulation of USP8 decreased apoptosis in Hucct-1 cells. Importantly, knockdown of USP8 inhibited activation of the Akt signaling pathway by decreasing the phosphorylation level of Akt and up-regulated p53 expression, while USP8 overexpression increased activation of the Akt signaling pathway in Hucct-1 cells. Further, IGF-1 could reverse the inhibitory effects of USP8 knockdown on the Akt signaling pathway and the proliferation of QBC939 and RBE cells.ConclusionTaken together, our findings suggest that USP8 exerts an oncogenic role in the progression of cholangiocarcinoma and may be a potential therapeutic target for cholangiocarcinoma treatment.

When does a pringle maneuver cause harm?

Presenter: Alexander Fagenson MD | Lewis Katz School of Medicine at Temple University Hospital Background: The Pringle Maneuver (PM) is considered to be safe and effective despite limited level one data to support its use. In addition, current evidence is mixed regarding postoperative outcomes. However, the PM has not been analyzed when stratified by extent of hepatectomy and pathology. Therefore, the aim of this analysis is to compare the outcomes of subsets of patients who have and have not undergone a PM in North America. Methods: Patients undergoing major hepatectomy (≥ 3 segments) or partial hepatectomy (≤ 2 segments) were identified in the 2014-17 ACS-NSQIP procedure-targeted database. Patients undergoing concomitant colon or another major resection were excluded. Subset analyses were performed based on hepatectomy extent and pathology type (metastatic disease and primary hepatobiliary malignancies). Outcomes of patients having a PM were compared to those with no PM after propensity score matching. Statistical analyses were performed by chi-square and Mann-Whitney U tests. Results: Prior to matching, 3,706 (24%) of 15,748 hepatectomies underwent a PM. PM was utilized in 1,445 (37%) of major hepatectomies and 2,261 (28%) of partial hepatectomies. PM was associated with worse outcomes (p < 0.05); however, these patients were significantly different at baseline. After matching, patients undergoing a PM during a partial hepatectomy had significantly increased rates of post-hepatectomy liver failure (PHLF), reintubation and septic shock (p < 0.05), but these differences were not observed in major hepatectomy patients (Table). In addition, patients with metastatic disease undergoing a PM had significantly increased rates of PHLF, septic shock and acute renal failure (p < 0.05) while these adverse outcomes did not develop in patients with primary hepatobiliary malignancies (Table). In each subset of patients operative time was significantly longer (p<0.05) when a PM was performed. Conclusion: The majority of hepatectomies are being performed without a Pringle Maneuver. The use of a Pringle Maneuver increases operative time and is associated with postoperative liver failure and septic shock. Patients undergoing a partial hepatectomy and those with metastatic disease have worse outcomes when a Pringle Maneuver is performed. The Pringle Maneuver is more likely to cause harm in patients undergoing smaller resections and in those with a more normal underlying liver.

Influence of obesity on in-hospital and postoperative outcomes of hepatic resection for malignancy: a 10-year retrospective analysis from the US National Inpatient Sample

ObjectivesThe influence of obesity on the outcomes of curative liver resection for malignancies remains controversial. We aimed to compare the in-hospital outcomes of liver resection for malignancy between obese and...

A single-center experience with 312 venous resections with pancreatectomy: Only elevated Ca 19-9 indicates impaired survival

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has emerged as an additional tool to increase the size of the future liver remnant (FLR) in the settings of advanced tumor burden in the liver. Initial reports have indicated high feasibility but also high mortality and morbidity. The aim of this study was to assess the initial experience with ALPPS in Scandinavia regarding feasibility, morbidity, and mortality.We conducted a retrospective analysis of all patients who underwent ALPPS since its introduction at 3 Scandinavian hepatobiliary centers.Thirty-six patients were identified, 21 male and 15 female. Median age was 67 years (22–83). Colorectal liver metastases (n = 25) were the most common indication for ALPPS followed by hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 4), and other (n = 3). Median growth of the FLR between the operations was 67% (−17 to 238) in 6 (5–13) days. All patients completed the second operation, and 71% of the resections were R0. Although the total percentage of patients with complication(s) was 92%, only 4 patients (11%) had a grade 3b complication according to the Clavien-Dindo classification, and no other severe complications were noted. There was no in-hospital mortality, but 1 (2.8%) patient died within 90 days of operation.ALPPS is a highly feasible method to stimulate FLR growth in patients with colorectal liver metastases as well as primary hepatobiliary malignancies. The treatment can be carried out with relative safety.

Risk factors for post-hepatectomy liver failure following resection of primary hepatobiliary versus metastatic cancer

Background: Post-hepatectomy liver failure (PHLF) is a significant source of morbidity and mortality following major hepatic resection. Prior studies evaluating risk factors for PHLF have focused on patients with primary liver malignancies, such as hepatocellular carcinoma (HCC), who often have associated underlying hepatic dysfunction. Hepatic dysfunction is less common in patients undergoing hepatectomy for metastatic disease and we hypothesized other risk factors may be associated with PHLF in this population. The aim of this study was to identify and compare pre-operative risk factors for PHLF between patients undergoing major hepatectomy for primary hepatobiliary (HPB) malignancy versus hepatic resection for metastatic disease. Methods: This study included patients who underwent elective major hepatectomy, defined as right-lobectomy or tri-segmentectomy, for primary HPB malignancy or metastatic disease from 2014–2016 from the National Surgical Quality Improvement Program (NSQIP) Hepatic database. The primary outcome was clinically significant PHLF (Grade B or C). Patient, disease, and pre-operative laboratory values were compared between patients with primary HPB malignancy or metastatic disease and their association with PHLF was evaluated. Separate multivariable logistic regression models for patients with primary HPB malignancy or metastatic disease were constructed to analyze risk factors for clinically significant PHLF and included all variables that were significant with an α less than 0.25 on univariate analysis. Results: From 2014–2016, 868 patients underwent major hepatectomy for primary HPB malignancy and 1,308 patients underwent major hepatectomy for metastatic cancer. Patients undergoing major hepatectomy for HPB malignancy were older (mean age 45.5 versus 40.5 years, p 10: 15.2% vs 4.7%, p < 0.001), and had lower pre-operative albumin levels (<3.5 g/dl: 18.6% vs 10.6%, p < 0.001) compared to those undergoing major hepatectomy for metastatic disease. PHLF occurred in 106 patients (12.2%) undergoing hepatectomy for HPB malignancy and in 71 patients (5.4%) undergoing hepatectomy for metastatic disease (p < 0.001). For patients with a primary HPB malignancy, low and high BMI (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.17-3.48 for <25 kg/m2, and OR, 2.49; 95% CI, 1.41-4.40 for ≥30 versus 25–29 kg/m2), cirrhotic liver texture (OR, 2.20; 95% CI, 1.15-4.24), MELD score ≥ 10 (OR, 1.86; 95% CI, 1.08-3.22), and diagnosis of gallbladder cancer and intrahepatic cholangiocarcinoma (IHC) (OR, 5.62; 95% CI, 2.01-15.71 for gallbladder cancer, and OR,1.85; 95% CI, 1.10-3.12 for IHC versus HCC) were associated with an increased odds of PHLF. For patients with metastatic disease, a diagnosis of diabetes (OR, 2.26; 95% CI, 1.22-4.18) and a pre-operative albumin <3.5 g/dl (OR, 2.51; 95% CI, 1.36-4.65) were associated with an increased odds of PHLF. Conclusion: Among patients who underwent major hepatectomy, the pre-operative risk factors for PHLF differ between patients with primary HPB malignancy and patients with metastatic cancer. While clinical factors such as a diagnosis of cirrhosis or an elevated MELD score are commonly used to identify patients at elevated risk for PHLF, neither MELD score nor cirrhosis are associated with PHLF in patients undergoing hepatectomy for metastatic disease as the incidence of these risk factors is very low in this population. In this study we identify diabetes and a low albumin level as independent factors strongly associated with an increased risk of PHLF in patients with metastatic cancer undergoing major hepatectomy, which should be considered in pre-operative planning and extent of hepatectomy for metastatic disease.

Extracellular Vesicles in Hepatobiliary Malignancies.

Primary hepatobiliary malignancies include a heterogeneous group of cancers with dismal prognosis, among which hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatoblastoma (HB) stand out. These tumors mainly arise from the malignant transformation of hepatocytes, cholangiocytes (bile duct epithelial cells) or hepatoblasts (embryonic liver progenitor cells), respectively. Early diagnosis, prognosis prediction and effective therapies are still a utopia for these diseases. Extracellular vesicles (EVs) are small membrane-enclosed spheres secreted by cells and present in biological fluids. They contain multiple types of biomolecules, such as proteins, RNA, DNA, metabolites and lipids, which make them a potential source of biomarkers as well as regulators of human pathobiology. In this review, the role of EVs in the pathogenesis of hepatobiliary cancers and their potential usefulness as disease biomarkers are highlighted. Moreover, the therapeutic value of EV regulation is discussed and future directions on basic and clinical research are indicated.

Challenges in consolidating the evidences of robotic surgery for primary hepatobiliary malignancies

We read “Long-term Oncologic Outcomes Following Robotic Liver Resections for Primary Hepatobiliary Malignancies: A Multicenter Study” with great interest. The report by Khan et al. provided a comprehensive analysis of various hepatobiliary cancers (1). Their data indicated that the robotic approach provided oncologic outcomes comparable to those reported previously with standard open and conventional laparoscopic approaches for primary liver and biliary malignancies. However, concerning the nature and different surgical demands of the various procedures, different liver and biliary malignancies shall be discussed in detail herein to clarify the role of the robotic platform.

Indications for transplantation and bridging procedures for primary hepatobiliary malignancies

Primary hepatobiliary malignancies are hepatocellular carcinoma, cholangiocarcinoma and the rare hepatocellular cholangiocarcinoma (mixed tumor). The indications for liver transplantation and the oncological prognosis differ considerably between these tumor entities. Treatment and decision making for these tumors are often complicated by an underlying chronic liver disease. The aim of this review is to delineate the indications for transplantation and bridging therapies for each cancer entity as well as to highlight some aspects pertinent to transplantation, such as the principles of organ allocation.

Long-Term Oncologic Outcomes Following Robotic Liver Resections for Primary Hepatobiliary Malignancies: A Multicenter Study.

Robotic liver surgery (RLS) has emerged as a feasible alternative to laparoscopic or open resections with comparable perioperative outcomes. Little is known about the oncologic adequacy of RLS. The purpose of this study was to investigate the long-term oncologic outcomes for patients undergoing RLS for primary hepatobiliary malignancies. We performed an international, multicenter, retrospective study of patients who underwent RLS for hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), or gallbladder cancer (GBC) between 2006 and 2016. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS), and overall survival (OS) were retrospectively collected and analyzed. Of the 61 included patients, 34 (56%) had RLS performed for HCC, 16 (26%) for CC, and 11 (18%) for GBC. The majority of resections were nonanatomical or segmental resections (39.3%), followed by central hepatectomy (18%), left-lateral sectionectomy (14.8%), left hepatectomy (13.1%), right hepatectomy (13.1%), and right posterior segmentectomy (1.6%). R0 resection was achieved in 94% of HCC, 68% of CC, and 81.8% of GBC patients. Median hospital stay was 5days, and conversion to open surgery was needed in seven patients (11.5%). Grade III-IV Dindo-Clavien complications occurred in seven patients with no perioperative mortality. Median follow-up was 75months (95% confidence interval 36-113), and 5-year OS and DFS were 56 and 38%, respectively. When stratified by tumor type, 3-year OS was 90% for HCC, 65% for GBC, and 49% for CC (p = 0.01). RLS can be performed for primary hepatobiliary malignancies with long-term oncologic outcomes comparable to published open and laparoscopic data.

Preoperative optimization for major hepatic resection.

Major hepatic resections are performed for primary hepatobiliary malignancies, metastatic disease, and benign lesions. Patients with chronic liver disease, including cirrhosis and steatosis, are at an elevated risk of malnutrition and impaired strength and exercise capacity, deficits which cause increased risk of postoperative complications and mortality. The aims of this report are to discuss the pathophysiology of changes in nutrition, exercise capacity, and muscle strength in patient populations likely to require major hepatectomy, and review recommendations for preoperative evaluation and optimization. Nutritional and functional impairment in preoperative hepatectomy patients, especially those with underlying liver disease, have a complex and multifactorial physiologic basis that is not completely understood. Recognition of malnutrition and compromised strength and exercise tolerance preoperatively can be difficult, but is critical in providing the opportunity to intervene prior to major hepatic resection and potentially improve postoperative outcomes. There is promising data on a variety of nutritional strategies to ensure adequate intake of calories, proteins, vitamins, and minerals in patients with cirrhosis and reduce liver size and degree of fatty infiltration in patients with hepatic steatosis. Emerging evidence supports structured exercise programs to improve exercise tolerance and counteract muscle wasting. The importance of nutrition and functional status in patients indicated for major liver resection is apparent, and emerging evidence supports structured preoperative preparation programs involving nutritional intervention and exercise training. Further research is needed in this field to develop optimal protocols to evaluate and treat this heterogeneous cohort of patients.

Duodenal Ulceration as a Complication of Yttrium-90 Microsphere Radioembolization of Intrahepatic Cholangiocarcinoma

Yttrium-90 (Y-90) microsphere radioembolization (RE) can be an effective regional treatment for primary hepatobiliary malignancies. RE with Y-90 has been described as safe for patients with intrahepatic cholangiocarcinoma (ICC)1. However, gastrointestinal ulceration is a rarely reported complication of Y-90 microsphere RE2. Given the increasing incidence of primary hepatobiliary tumors and an expected rise in use of Y-90 RE, we present a case of Y-90 RE-associated duodenal ulceration. A 76-year-old woman presented to the hospital with lower abdominal pain and was evaluated with a CT scan which revealed an ill-defined liver mass adjacent to the gallbladder which was diagnosed as stage IV intrahepatic cholangiocarcinoma involving segment 4 of the liver. She was treated with Y-90 RE with the intent of tumor down-sizing prior to resection. As part of the treatment application, the gastroduodenal artery was densely packed with coils with complete stasis of flow achieved. Through the medial branch of the left hepatic artery, the Y-90 spheres were super-selectively deployed through a micro-catheter. Two months after the radioembolization, she experienced mid-epigastric abdominal pain, not responsive to proton pump inhibitor. Upper endoscopy revealed two non-bleeding superficial duodenal ulcers with no stigmata of bleeding in the duodenal bulb. Pathology from biopsies of the ulcer bed revealed the presence of Y-90 beads in the lamina propria, consistent with radiation-induced duodenitis. She is currently being treated with high dose proton pump inhibitor (PPI) therapy by mouth twice daily, with good response. This case highlights a potential complication associated with radioactive microsphere embolization. Given the increasing use of this treatment modality, gastroenterologists should recognize this entity, and its delayed occurrence in particular. New-onset, or change in abdominal discomfort or pain should prompt endoscopic evaluation in patients with prior Y-90 RE. We suggest high dose PPI therapy as initial management, but the optimal treatment strategy to treat gastrointestinal ulceration as a complication of RE should be further investigated.

Portal Vein Thrombosis in the Setting of Newly Diagnosed Cushing's Syndrome.

The hallmark manifestations of Cushing’s syndrome (CS) are well known, but hypercoagulability is perhaps least recognized. Patients with CS are at increased risk of both spontaneous and postoperative thromboembolism, with the significant majority of events occurring in the lower extremity and pulmonary venous circulations. We present a case of portal vein thrombosis (PVT) occurring in the setting of newly diagnosed CS due to a left adrenal adenoma. Factor VIII activity was approximately 2.5-fold elevated, a known mechanism by which hypercortisolemia predisposes to venous thrombosis. Acute abdominal pain and fever responded well to unfractionated heparin and parenteral antibiotics, and CS was eventually cured by left adrenalectomy. No thromboembolic events have occurred since surgery. PVT is uncommon and usually occurs as a complication of primary or secondary hepatobiliary malignancies and cirrhosis. To the best of our knowledge, this is just the second reported case of PVT due to CS and the first published in the English language literature.