Novel combination approaches to locoregional and systemic therapy in the management of primary and metastatic liver tumors.

Several pathways and mutations must develop or be in place for the onset of cancer. Therefore, therapies should ideally target as many of these pathways as possible to improve outcomes. Combining several agents has proven to be more effective than the use of monotherapy in the treatment of renal cell carcinoma, hepatocellular carcinoma, and other cancers. Combination therapy can also include locoregional therapies such as ablation and embolization with systemic agents for synergistic effects. This review article discusses the current literature and clinical trials covering these multifactorial combination therapies in primary and metastatic liver tumors.

Perioperative blood transfusion is associated with an increased risk for post-surgical infection following pancreaticoduodenectomy.

BACKGROUND/PURPOSE: Perioperative blood transfusion is common after pancreaticoduodenectomy (PD) and may predispose patients to infectious complications. The purpose of this study is to examine the association between perioperative blood transfusion and the development of post-surgical infection after PD. METHODS: Patients who underwent PD from 2014 to 2015 were identified in the NSQIP pancreas-specific database. Logistic regression analysis was used to compute adjusted odds ratios (aOR) to identify an independent association between perioperative red blood cell transfusion (within 72 h of surgery) and the development of post-operative infection after 72 h. RESULTS: A total of 6869 patients underwent PD during this time period. Of these, 1372 (20.0%) patients received a perioperative blood transfusion. Patients receiving transfusion had a higher rate of post-operative infection (34.7% vs 26.5%, p < 0.001). After adjusting for significant covariates, perioperative transfusion was independently associated the subsequent development of any post-operative infection (aOR 1.41 [1.23-1.62], p < 0.001), including pneumonia (aOR 2.01 [1.48-2.74], p < 0.001), sepsis (aOR 1.62 [1.29-2.04], p < 0.001), and septic shock (aOR 1.92 [1.38-2.68], p < 0.001). CONCLUSION: There is a strong independent association between perioperative blood transfusion and the development of subsequent post-operative infection following PD.

Significance and Prevalence of Haziness Surrounding the Hepatic Artery and Celiac Axis on Computed Tomographic Imaging After Pancreaticoduodenectomy.

PURPOSE: This study was conducted to assess the prevalence and significance of "haziness" around the hepatic artery and celiac axis in patients after pancreaticoduodenectomy. METHODS: This retrospective study was conducted on 116 patients who underwent pancreaticoduodenectomy or a similar procedure and had no clinical evidence of tumor recurrence or malignancy within 2 years from the date of surgery. RESULTS: Most images exhibited at least mild to moderate haziness around the hepatic artery and celiac axis. Patients with benign vs malignant results on formal pathology had no significant difference in severity of findings. Haziness remained in the mild to moderate range 2 years after surgery. CONCLUSIONS: Mild to moderate soft tissue stranding with increased attenuation around the hepatic artery and celiac axis is a common finding after pancreaticoduodenectomy that may persist for years after surgery. Such haziness alone has low specificity for tumor recurrence and should not be regarded as an indicator of malignancy.

Global Estimation of Surgical Procedures Needed for Forcibly Displaced Persons.

INTRODUCTION: Sixty million people were displaced from their homes due to conflict, persecution, or human rights violations at the end of 2014. This vulnerable population bears a disproportionate burden of disease, much of which is surgically treatable. We sought to estimate the surgical needs for forcibly displaced persons globally to inform humanitarian assistance initiatives. METHODS: Data regarding forcibly displaced persons, including refugees, internally displaced persons (IDPs), and asylum seekers were extracted from United Nations databases. Using the minimum proposed surgical rate of 4669 procedures per 100,000 persons annually, global, regional, and country-specific estimates were calculated. The prevalence of pregnancy and obstetric complications were used to estimate obstetric surgical needs. RESULTS: At least 2.78 million surgical procedures (IQR 2.58-3.15 million) were needed for 59.5 million displaced persons. Of these, 1.06 million procedures were required in North Africa and the Middle East, representing an increase of 50 % from current unmet surgical need in the region. Host countries with the highest surgical burden for the displaced included Syria (388,000 procedures), Colombia (282,000 procedures), and Iraq (187,000). Between 4 and 10 % of required procedures were obstetric surgical procedures. Children aged <18 years made up 52 % of the displaced, portending a substantial demand for pediatric surgical care. CONCLUSION: Approximately three million procedures annually are required to meet the surgical needs of refugees, IDPs, and asylum seekers. Most displaced persons are hosted in countries with inadequate surgical care capacity. These figures should be considered when planning humanitarian assistance and targeted surgical capacity improvements.

Vascular reconstruction plays an important role in the treatment of pancreatic adenocarcinoma.

OBJECTIVE: Previous studies have proved the feasibility of performing a pancreaticoduodenectomy (Whipple operation) in patients with portal vein-superior mesenteric vein and hepatic artery invasion. We report our institutional experience with the use of a variety of vascular reconstructive methods during pancreatic resections for adenocarcinoma. METHODS: A retrospective review was performed identifying all patients undergoing a Whipple operation or total pancreatectomy procedure from January 2003 to December 2013. All venous (portal vein-superior mesenteric vein) and arterial (superior mesenteric artery-hepatic artery) reconstructions were extracted and reviewed to determine survival and perioperative complications. RESULTS: During the 10-year study period, 270 Whipple and total pancreatectomy procedures were performed, of which 183 were for adenocarcinoma of the pancreas. Of the 183 operations, a total of 60 (32.8%) vascular reconstructions were found, 49 venous and 11 arterial. Venous reconstruction included 37 (61.7%) primary repairs, four (6.7%) reconstructions with CryoVein (CryoLife, Inc, Kennesaw, Ga), three (5.0%) repairs with autologous vein patch, three (5.0%) autologous saphenous reconstructions, and two (3.33%) portacaval shunts. In addition, there were 11 (18.3%) arterial reconstructions (seven hepatic artery and four superior mesenteric artery). The 1-year survival for all reconstructions was 71.1%, which is equivalent to T3 lesions that did not receive vascular reconstruction (70.11%), with a median survival time of 575.28 days and 12 patients still alive. Survival time was comparable with each type of venous reconstruction, averaging 528 days (11 of 49 patients still alive). There was a total thrombosis rate of seven of 60 (11.6%), all of which were portal vein thrombosis: three in the primary repair group and four delayed thromboses seen in primary repair, CryoVein repair, and vein patch repair. There was no thrombosis in any patients after arterial reconstruction. CONCLUSIONS: An aggressive approach for stage II pancreatic cancers with venous or arterial invasion can be performed with comparable results when it is executed by an experienced institution with skilled oncologic and vascular surgeons.

Closed-loop assisted versus manual goal-directed fluid therapy during high-risk abdominal surgery: a case-control study with propensity matching.

INTRODUCTION: Goal-directed fluid therapy strategies have been shown to benefit moderate- to high-risk surgery patients. Despite this, these strategies are often not implemented. The aim of this study was to assess a closed-loop fluid administration system in a surgical cohort and compare the results with those for matched patients who received manual management. Our hypothesis was that the patients receiving closed-loop assistance would spend more time in a preload-independent state, defined as percentage of case time with stroke volume variation less than or equal to 12%. METHODS: Patients eligible for the study were all those over 18 years of age scheduled for hepatobiliary, pancreatic or splenic surgery and expected to receive intravascular arterial blood pressure monitoring as part of their anesthetic care. The closed-loop resuscitation target was selected by the primary anesthesia team, and the system was responsible for implementation of goal-directed fluid therapy during surgery. Following completion of enrollment, each study patient was matched to a non-closed-loop assisted case performed during the same time period using a propensity match to reduce bias. RESULTS: A total of 40 patients were enrolled, 5 were ultimately excluded and 25 matched pairs were selected from among the remaining 35 patients within the predefined caliper distance. There was no significant difference in fluid administration between groups. The closed-loop group spent a significantly higher portion of case time in a preload-independent state (95 ± 6% of case time versus 87 ± 14%, P =0.008). There was no difference in case mean or final stroke volume index (45 ± 10 versus 43 ± 9 and 45 ± 11 versus 42 ± 11, respectively) or mean arterial pressure (79 ± 8 versus 83 ± 9). Case end heart rate was significantly lower in the closed-loop assisted group (77 ± 10 versus 88 ± 13, P =0.003). CONCLUSION: In this case-control study with propensity matching, clinician use of closed-loop assistance resulted in a greater portion of case time spent in a preload-independent state throughout surgery compared with manual delivery of goal-directed fluid therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02020863. Registered 19 December 2013.

Perioperative goal-directed therapy and postoperative outcomes in patients undergoing high-risk abdominal surgery: a historical-prospective, comparative effectiveness study.

INTRODUCTION: Perioperative goal-directed therapy (PGDT) may improve postoperative outcome in high-risk surgery patients but its adoption has been slow. In 2012, we initiated a performance improvement (PI) project focusing on the implementation of PGDT during high-risk abdominal surgeries. The objective of the present study was to evaluate the effectiveness of this intervention. METHODS: This is a historical prospective quality improvement study. The goal of this initiative was to standardize the way fluid management and hemodynamic optimization are conducted during high-risk abdominal surgery in the Departments of Anesthesiology and Surgery at the University of California Irvine. For fluid management, the protocol consisted in standardized baseline crystalloid administration of 3 ml/kg/hour and any additional boluses based on PGDT. The impact of the intervention was assessed on the length of stay in the hospital (LOS) and post-operative complications (NSQIP database). RESULTS: In the 1 year pre- and post-implementation periods, 128 and 202 patients were included. The average volume of fluid administered during the case was 9.9 (7.1-13.0) ml/kg/hour in the pre-implementation period and 6.6 (4.7-9.5) ml/kg/hour in the post-implementation period (p < 0.01). LOS decreased from 10 (6-16) days to 7 (5-11) days (p = 0.0001). Based on the multiple linear regression analysis, the estimated coefficient for intervention was 0.203 (SE = 0.054, p = 0.0002) indicating that, with the other conditions being held the same, introducing intervention reduced LOS by 18% (95% confidence interval 9-27%). The incidence of NSQIP complications decreased from 39% to 25% (p = 0.04). CONCLUSION: These results suggest that the implementation of a PI program focusing on the implementation of PGDT can transform fluid administration patterns and improve postoperative outcome in patients undergoing high-risk abdominal surgeries. TRIAL REGISTRATION: Clinicaltrials.gov NCT02057653. Registered 17 December 2013.

Surgery for gallstone ileus: a nationwide comparison of trends and outcomes.

INTRODUCTION: Gallstone ileus is a mechanical bowel obstruction caused by a biliary calculus originating from a bilioenteric fistula. Because of the limited number of reported cases, the optimal surgical method of treatment has been the subject of ongoing debate. METHODS: A retrospective review of the Nationwide Inpatient Sample from 2004 to 2009 was performed for gallstone ileus cases treated surgically by enterotomy with stone extraction alone (ES), enterotomy and cholecystectomy with fistula closure (EF), bowel resection alone (BR), and bowel resection with fistula closure (BF). Patient demographics, hospital factors, comorbidities, and postoperative outcomes were reported. Multivariate analysis was performed comparing mortality, morbidity, length of stay, and total cost for the different procedure types. RESULTS: Of the estimated 3,452,536 cases of mechanical bowel obstruction from 2004 to 2009, 3268 (0.095%) were due to gallstone ileus-an incidence lower than previously reported. The majority of patients were elderly women (>70%). ES was the most commonly performed procedure (62% of patients) followed by EF (19% of cases). In 19%, a bowel resection was required. The most common complication was acute renal failure (30.44% of cases). In-hospital mortality was 6.67%. On multivariate analysis, EF and BR were independently associated with higher mortality than ES [(odds ratio [OR] = 2.86; confidence interval [CI]: 1.16-7.07) and (OR = 2.96; CI: 1.26-6.96) respectively]. BR was also associated with a higher complication rate, OR = 1.98 (CI: 1.13-3.46). CONCLUSIONS: Gallstone ileus is a rare surgical disease affecting mainly the elderly female population. Mortality rates appear to be lower than previously reported in the literature. Enterotomy with stone extraction alone appears to be associated with better outcomes than more invasive techniques.

Delayed gastric emptying is associated with increased risk of mortality in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

Delayed gastric emptying (DGE) is common in patients undergoing pancreaticoduodenectomy (PD). The effect of DGE on mortality is less clear. We sought to identify predictors of mortality in patients undergoing PD for pancreatic adenocarcinoma hypothesizing DGE to independently increase risk of 30-day mortality. The ACS-NSQIP targeted pancreatectomy database (2014-2017) was queried for patients with pancreatic adenocarcinoma undergoing PD. A multivariable logistic regression analysis was performed. Separate sensitivity analyses were performed adjusting for postoperative pancreatic fistula (POPF) grades A-C. Out of 8011 patients undergoing PD, 1246 had DGE (15.6%). About 8.5% of patients with DGE had no oral intake by postoperative day-14. The DGE group had a longer median operative duration (373 vs. 362 min, p = 0.019), and a longer hospital length of stay (16.5 vs. 8 days, p < 0.001). After adjusting for age, gender, comorbidities, preoperative chemotherapy, preoperative radiation, open versus laparoscopic approach, vascular resection, deep surgical space infection (DSSI), postoperative percutaneous drain placement, and development of a POPF, DGE was associated with an increased risk for 30-day mortality (OR 3.25, 2.16-4.88, p < 0.001). On sub-analysis, grades A and B POPF were not associated with risk of mortality while grade C POPF was associated with increased risk of mortality (OR 5.64, 2.24-14.17, p < 0.001). The rate of DGE in patients undergoing PD in this large database was over 15%. DGE is associated with greater than three times the increased associated risk of mortality, even when controlling for POPF, DSSI, and other known predictors of mortality.

Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma.

Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.

Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model.

Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.

Safety and efficacy of trans arterial chemoembolization with drug-eluting beads in hepatocellular cancer: a systematic review.

BACKGROUND/AIMS: The aim of this review was to compare current conventional TACE to the drug eluting beads loaded with doxorubicin (DEBDOX) device in the treatment of HCC. METHODOLOGY: A recent hepatocellular consensus discussion was convened to review all recent and past literature in the use of hepatic directed therapies to compare the safety, efficacy and overall survival of the available hepatic directed therapies in the management of hepatocellular cancer. A review of all publications in peer review journals in the English Language from 1995 to 2007 was performed. RESULTS: The DEBDOX are an effective therapy with a favorable pharmacokinetic profile with significantly less systemic doxorubicin exposure when compared to conventional TACE. The DEBDOX had a significant (p<0.05) advantage in objective response in the more advanced patients (defined as Child-Pugh B, ECOG 1, recurrent disease and bilobar disease; p=0.038) and overall disease control in the more advanced patients (p=0.026). The DEBDOX Bead was also found to have a highly significant (p<0.01) advantage in the reduction of doxorubicin associated side effects (p=0.0001) in all patients. CONCLUSIONS: The current collective data on the use of DEBDOX Bead in HCC patients provides sufficient evidence to support its use as a safe and effective chemo-embolic treatment in intermediate HCC patients. There is growing evidence to support the its use is superior to conventional doxorubicin TACE.

Intra-Operative Abdominal Drain Placement for Gallbladder Cancer Surgery and Risk of Infectious Complications.

Background: Routine intra-operative abdominal drain placement (IADP) is not beneficial for uncomplicated cholecystectomies though outcomes in gallbladder cancer surgery is unclear. This retrospective study hypothesized that patients with IADP (+IADP) for gallbladder cancer surgery have a higher risk of post-operative infectious complications (PIC) compared with patients without IADP (-IADP). Patients and Methods: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for +IADP and -IADP patients who had gallbladder cancer surgery. Post-operative infectious complications were defined as septic shock, organ/space infection (OSI), or percutaneous drainage. Multivariable analyses were performed to analyze the associated risk of PIC. Results: Of 385 patients, 237 (61.6%) were +IADP. The +IADP patients had higher rates of post-operative bile leak, OSI, re-admission, and increased length of stay (p < 0.05). The +IADP patients were not associated with increased risk of PIC (p > 0.05). Bile leak (odds ratio [OR], 10.61; p < 0.001), peri-operative blood transfusion (OR, 3.77; p = 0.003), biliary reconstruction (OR, 2.88; p = 0.018), and pre-operative biliary stent placement (OR, 3.02; p = 0.018) were the strongest associated risk factors of PIC. Patients with drains in place at or longer than 30 days post-operatively had an increased associated risk compared with patients who did not (OR, 6.88; 95% confidence interval [CI], 2.16-21.86; p < 0.001). Conclusions: More than 60% of gallbladder cancer surgeries included IADP and was not associated with an increased risk of PIC. Intra-operative abdominal drain placement was not associated with an increased risk of PIC, unless drains were left in place for 30 days or longer. Increased risk of PIC was associated with bile leak, peri-operative blood transfusion, pre-operative biliary stent placement, and biliary reconstruction.

Surgical management of recurrent ovarian cancer: the advantage of collaborative surgical management and a multidisciplinary approach.

OBJECTIVE: Primary cytoreductive surgery is well accepted in the initial management of ovarian cancer with a goal of maximal tumor reduction. The role of cytoreductive surgery at disease recurrence is controversial and guidelines are not standardized. We aimed to review cases of women with recurrent ovarian cancer who were collaboratively managed by two teams of oncologic surgeons with different areas of surgical expertise. METHODS: A list of 616 patients with recurrent ovarian cancer from 1995 to 2009 was generated at a single institution. 20 cases of recurrent ovarian cancer were identified that were managed collaboratively. Data collected included date of diagnosis, initial treatment, recurrence date, location and number of sites of recurrence, secondary cytoreductive procedure performed, residual disease after surgery, pre-operative status, post-operative course, and pathologic findings. RESULTS: Of the 20 cases that fit eligibility criteria, 11 were completely resected, 5 were incompletely resected, and 4 were biopsied only. Median disease-free interval following primary surgery was 18 months (6-147). Median interval from diagnosis to collaborative cytoreduction was 63 months (13-170). Our patients had metastatic disease to the liver (11), lymph nodes (8), the diaphragm (7), other locations including colon, pancreas, lung, adrenal, kidney (9). Two patients had additional miliary disease. All patients underwent joint surgical management by gynecologic and surgical oncologists. There were no deaths in the immediate post-operative period. The 5 year survival rate was 45% following the joint surgical effort, with a median post-collaborative surgery survival duration of 42 months. CONCLUSIONS: Previous studies document survival benefit of surgery for women with recurrent ovarian cancer when there has been a long disease-free interval, localized pelvic or intra-abdominal recurrences and an optimal performance status. Most gynecologic oncologists do not perform extensive liver or diaphragm resections or lymph node excision above the renal vessels; thus, collaboration with a surgical oncologist is a viable option. In this small descriptive study, the feasibility of this reasonably well-tolerated approach, with possible survival benefit, is documented.

Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma.

BACKGROUND: Tirapazamine (TPZ) is a hypoxia activated drug that may be synergistic with transarterial embolization (TAE). The primary objective was to evaluate the safety of combining TPZ and TAE in patients with unresectable HCC and determine the optimal dose for Phase II. METHODS: This was a Phase 1 multicenter, open-label, non-randomized trial with a classic 3+3 dose escalation and an expansion cohort in patients with unresectable HCC, Child Pugh A, ECOG 0 or 1. Two initial cohorts consisted of I.V. administration of Tirapazamine followed by superselective TAE while the remaining three cohorts underwent intraarterial administration of Tirapazamine with superselective TAE. Safety and tolerability were assessed using NCI CTCAE 4.0 with clinical, imaging and laboratory examinations including pharmacokinetic (PK) analysis and an electrocardiogram 1 day pre-dose, at 1, 2, 4, 6, 10, and 24 hours post-TPZ infusion and an additional PK at 15- and 30-minutes post-TPZ. Tumor responses were evaluated using mRECIST criteria. RESULTS: Twenty-seven patients (mean [range] age of 66.4 [37-79] years) with unresectable HCC were enrolled between July 2015 and January 2018. Two patients were lost to follow-up. Mean tumor size was 6.53 cm ± 2.60 cm with a median of two lesions per patient. Dose limiting toxicity and maximum tolerated dose were not reached. The maximal TPZ dose was 10 mg/m2 I.V. and 20 mg/m2 I.A. One adverse event (AE) was reported in all patients with fatigue, decreased appetite or pain being most common. Grade 3-5 AE were hypertension and transient elevation of AST/ALT in 70.4% of patients. No serious AE were drug related. Sixty percent (95% CI=38.7-78.9) achieved complete response (CR), and 84% (95% CI=63.9-95.5) had complete and partial response per mRECIST for target lesions. DISCUSSION: TAE with TPZ was safe and tolerable with encouraging results justifying pursuit of a Phase II trial.

The clinical presentation of chronic hepatitis B virus infection in Asian Americans: a single center retrospective study.

BACKGROUND: The clinical course of chronic hepatitis B virus (HBV) infection varies with ethnicity. Little is known about the clinical presentation of chronic HBV infection in Asian Americans. OBJECTIVES: To define the clinical presentation of chronic HBV infection in Asian Americans. METHODS: This is a retrospective study that used systematic chart review and statistical analysis to investigate 213 Asian-American patients with chronic HBV infection who presented to a university medical center. RESULTS: This cohort included 55.8% male patients, 97.9% were born outside the US, and 52.3% reported a family history of HBV infection. Of the 56 patients with liver biopsy, 34.0% had stage 3 to 4 fibrosis. In patients with available data, 21.5% were hepatitis B e antigen positive [HBeAg (+)] and 31.1% had HBV DNA levels >1 x 10(6) copies/mL. Patients with HBeAg (+) HBV infection were diagnosed at a younger age (P=0.002) and with higher alanine aminotransferase (P=0.001) and HBV DNA (P=0.001) levels. Although only 3.3% presented with obesity (ie, body mass index >or=30 kg/m2), 43.4% had evidence of hepatic steatosis. Presentation of hepatocellular carcinoma was associated with an older age at diagnosis (P<0.001), male sex (P<0.001), tobacco use (P<0.001), a greater degree of fibrosis on liver biopsy (P=0.01), and higher alanine aminotransferase, aspartate aminotransferase (P<0.001), and a fetoprotein (P<0.001) levels. CONCLUSIONS: Chronic HBV infection in foreign-born Asian Americans was characterized by a low rate of HBeAg (+) and male predominance as well as high rates of family history of HBV infection, hepatic fibrosis, and hepatic steatosis.

Spontaneous choledochoduodenal fistula in a patient with a bile duct injury following laparoscopic cholecystectomy.

We report a 67-year-old female that had a laparoscopic cholecystectomy complicated by common bile duct (CBD) and right hepatic artery injuries. A catheter was placed into the proximal common bile duct to create an external biliary fistula. The catheter eroded into the edge of the CBD and that irritation caused a choledochoduodenal fistula to form. To our knowledge, this is the first reported case in which an external biliary catheter caused the formation of a choledochoduodenal fistula after a bile duct injury from a laparoscopic cholecystectomy.

Bile Metabolism and Lithogenesis: An Update.

Bile is composed of multiple macromolecules, including bile acids, free cholesterol, phospholipids, bilirubin, and inorganic ions that aid in digestion, nutrient absorption, and disposal of the insoluble products of heme catabolism. The synthesis and release of bile acids is tightly controlled and dependent on feedback mechanisms that regulate enterohepatic circulation. Alterations in bile composition, impaired gallbladder relaxation, and accelerated nucleation are the principal mechanisms leading to biliary stone formation. Various physiologic conditions and disease states alter bile composition and metabolism, thus increasing the risk of developing gallstones.

Systematic review of islet cryopreservation.

Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets. After exposure to the freezing and thawing, islets are usually either apoptotic, non-functional, or non-viable. Several studies have proposed various techniques that could lead to increased cell survival and function following a deep freeze. The purpose of this article is to critically review the techniques of islet cryopreservation, with the goal of highlighting optimization parameters that can lead to the most viable and functional islet upon recovery and/or transplant.