Pretreatment Health-Related Quality-of-Life Status and Survival in Pancreatobiliary Surgical Patients.

BACKGROUND: Pancreatobiliary (PB) disorders, especially cancer, negatively affect patients' health-related quality of life (HRQoL). However, the influence of baseline, preintervention HRQoL on perioperative and oncologic outcomes has not been well defined. We hypothesized that low baseline HRQoL is associated with worse perioperative and long-term survival outcomes for PB surgical patients. STUDY DESIGN: Pretreatment Functional Assessment of Cancer Therapy - Hepatobiliary Survey results and clinical data from PB patients (2008 to 2016) from a single center's prospective database were analyzed. Survey responses were aggregated into composite scores and divided into quintiles. Patients in the highest quintile of HRQoL were compared to patients in the bottom four quintiles combined. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Logistic and Cox regressions were used to determine associations between quintiles of HRQoL scores and 30-day complications and long-term survival, respectively. RESULTS: Of 162 patients evaluated, 99 had malignancy, and 63 had benign disease. Median follow-up was 31 months. Baseline HRQoL scores were similar for benign and malignant disease (p = 0.42) and were not associated with the development of any (p = 0.08) or major complications (p = 0.64). Patients with highest quintile HRQoL scores had improved 3-year OS (84.6 vs 61.7%, p = 0.03) compared to patients in the lowest four quintiles of HRQoL. Among cancer patients only, those with the highest quintile scores had improved 3-year OS (81.6 vs 47.4%, p = 0.02). On multivariable analysis, highest quintile HRQoL scores were associated with longer OS and DFS for patients with malignancy. CONCLUSIONS: Pretreatment HRQoL was associated with both OS and DFS among PB patients and might have prognostic utility. Future studies are necessary to determine whether patients with poorer HRQoL may benefit from targeted psychosocial interventions.

Ampullary Carcinosarcoma with Enteroblastic Differentiation: A Case Report.

Adenocarcinoma with enteroblastic differentiation is an extremely rare tumor with poor prognosis and unique pathologic features. The tumor appears to be relatively more common in stomach, with rare cases reported in esophagus, colon, rectum and ampulla. Underrecognition by pathologists may be a contributing factor towards underreporting of this tumor. Combination of carcinosarcoma and enteroblastic differentiation has not been reported so far.We report a unique case of ampullary carcinosarcoma with enteroblastic differentiation in a 59-year-old female, diagnosed in the pancreatoduodenectomy specimen. The carcinomatous component showed features of enteroblastic differentiation characterized by tubular architecture with clear cytoplasm, solid component with trabecular architecture and immunohistochemical expression of SALL4 and AFP. The patient was treated with adjuvant Folfirinox chemotherapy and is disease free at 17 months follow up.

B7-H3 targeted antibody-based immunotherapy of malignant diseases.

Introduction: Recent advances in immuno-oncology and bioengineering have rekindled the interest in monoclonal antibody (mAb)-based immunotherapies for malignancies. Crucial for their success is the identification of tumor antigens (TAs) that can serve as targets. B7-H3, a member of the B7 ligand family, represents such a TA. Although its exact functions and receptor(s) remain unclear, B7-H3 has predominantly a pro-tumorigenic effect mainly by suppressing the anti-tumor functions of T-cells.Areas covered: Initially we present a historical perspective on TA-specific antibodies for diagnosis and treatment of malignancies. Following a description of the TA requirements to be an attractive antibody-based immunotherapy target, we show that B7-H3 fulfills these criteria. We discuss its structure and functions. In a review and pooled analysis, we describe the limited B7-H3 expression in normal tissues and estimate B7-H3 expression frequency in tumors, tumor-associated vasculature and cancer initiating cells (CICs). Lastly, we discuss the association of B7-H3 expression in tumors with poor prognosis.Expert opinion: B7-H3 is an attractive target for mAb-based cancer immunotherapy. B7-H3-targeting strategies are expected to be highly effective and - importantly - safe. To fully exploit the diagnostic and therapeutic potential of B7-H3, its expression in pre-malignant lesions, serum, metastases, and CICs requires further investigation.

Medical Tourism and Diabetes Care: Experience from a Tertiary Referral Center.

OBJECTIVE: Medical tourism, a form of patient mobility across international borders to seek medical services, has gained significant momentum. We aimed to assess the outcomes of medical tourism consultations on chronic diseases, more specifically diabetes mellitus, amongst a cohort of international patients, originating from different healthcare systems, and referred to the United States for medical care. METHODS: We identified international adults with established diabetes mellitus, referred globally from 6 countries to the United States between 2010 and 2016 for medical care, and were seen at the Cleveland Clinic Foundation (CCF). Group 1 included adults seen by an endocrinology provider during their CCF medical stay, whilst group 2 included those not seen by an endocrinology provider. To assess the impact of our consultations, changes in hemoglobin A1c (HbA1c) were assessed between visit(s). RESULTS: Our study included 1,108 subjects (771 in group 1, 337 in group 2), with a mean age (± SD) of 61.3±12.7 years, 62% male, and a median medical stay of 136 days (interquartile range: 57, 660). Compared to group 2, group 1 had a higher baseline mean HbA1c (8.0 ± 1.8% [63.9 mmol/mol] vs. 7.1 ± 1.4% [54.1 mmol/mol]; P<.001). After 1 visit with endocrinology, there was a significant decrease in mean HbA1c from 8.44 ± 1.98% (68.3 mmol/mol) to 7.51 ± 1.57% (58.5 mmol/mol) (P<.001). Greatest reductions in mean HbA1c were -1.47% (95% CI: -2.21, -0.74) and -1.27% (95% CI: -1.89, -0.66) after 3 and 4 visits, respectively (P<.001). CONCLUSION: Short-term diabetes mellitus consultations, in the context of medical tourism, are effective.

Evidence Versus Practice in Early Drain Removal After Pancreatectomy.

BACKGROUND: Early drain removal when postoperative day (POD) one drain fluid amylase (DFA) was ≤5000 U/L reduced complications in a previous randomized controlled trial. We hypothesized that most surgeons continue to remove drains late and this is associated with inferior outcomes. METHODS: We assessed the practice of surgeons in a prospectively maintained pancreas surgery registry to determine the association between timing of drain removal with demographics, comorbidities, and complications. We selected patients with POD1 DFA ≤5000 U/L and excluded those without drains, and subjects without data on POD1 DFA or timing of drain removal. Early drain removal was defined as ≤ POD5. RESULTS: Two hundred and forty four patients met inclusion criteria. Only 90 (37%) had drains removed early. Estimated blood loss was greater in the late removal group (190 mL versus 100 mL, P = 0.005) and pathological findings associated with soft gland texture were more frequent (97 [63%] versus 35 [39%], P < 0.0001). Patients in the late drain removal group had more complications (84 [55%] versus 30 [33%], P = 0.001) including pancreatic fistula (55 [36%] versus 4 [4%], P < 0.0001), delayed gastric emptying (27 [18%] versus 3 [3%], P = 0.002), and longer length of stay (7 d versus 5 d, P < 0.0001). In subset analysis for procedure type, complications and pancreatic fistula remained significant for both pancreatoduodenectomy and distal pancreatectomy. CONCLUSIONS: Despite level one data suggesting improved outcomes with early removal when POD1 DFA is ≤ 5000 U/L, experienced pancreas surgeons more frequently removed drains late. This practice was associated with known risk factors (estimated blood loss, soft pancreas) and may be associated with inferior outcomes suggesting potential for improvement.

Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy.

BACKGROUND: Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management. METHODS: In this retrospective cohort study of 4,404 patients aged 18-79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004-2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression. RESULTS: Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log-rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89-1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55-0.74). CONCLUSION: The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher-stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease.

Evidence-Based Management of Drains Following Pancreatic Resection: A Systematic Review.

Many pancreatic surgeons continue to use intraperitoneal drains, but others have limited or avoided their use, believing this improves outcomes. We conducted a systematic review and meta-analysis of the literature assessing outcomes in pancreatectomy without drains, selective drainage, and early drain removal. We searched PubMed, Embase, and the Cochrane Library databases and conducted a systematic review of randomized and nonrandomized studies comparing routine intra-abdominal drainage versus no drainage, selective drain use, and early versus late drain removal after pancreatectomy, with major complications as the primary outcome. A meta-analysis of the literature assessing routine use of drains was conducted using the random-effects model. A total of 461 articles met search criteria from PubMed (168 articles), Embase (263 articles), and the Cochrane Library (30 articles). After case reports and articles without primary data on complications were excluded, 14 studies were identified for systematic review. Definitive evidence-based recommendations cannot be made regarding the management of drains following pancreatectomy because of limitations in the available literature. Based on available evidence, the most conservative approach, pending further data, is routine placement of a drain and early removal unless the patient's clinical course or drain fluid amylase concentration suggests a developing fistula.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage.

OBJECTIVE: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

Proximal Roux-en-y Gastrojejunal Anastomosis with Pyloric Ring Resection Improves Gastric Emptying After Pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication of pancreaticoduodenectomy. We determined the efficiency of a new reconstruction technique, designed to preserve motilin-secreting cells and maximize the utility of their receptors, in reducing the incidence of DGE after pancreaticoduodenectomy. METHODS: From April 2005 to September 2014, 217 consecutive patients underwent pancreaticoduodenectomy at our institution. Nine patients who underwent total pancreatectomy were excluded. We compared outcomes between patients who underwent pancreaticoduodenectomy with resection of the pyloric ring followed by proximal Roux-en-y gastrojejunal anastomosis (group I, n = 90) and patients who underwent standard pancreaticoduodenectomy with the orthotopic reconstruction technique (group II, n = 118). RESULTS: Overall and clinically relevant rates of DGE were significantly lower in group I than in group II (10 and 2.2 % vs. 57 and 24 %, respectively; p < 0.05). Length of hospital stay as a result of DGE was shorter in group I than in group II. In univariate analysis, older age, comorbidities, ASA grade 4, operative time, preoperative diabetes, standard reconstruction technique, and postoperative complications were significant risk factors for DGE. In multivariate analysis, older age, standard technique, and postoperative complications were independent risk factors for DGE. CONCLUSION: Our new reconstruction technique reduces the occurrence of DGE after pancreaticoduodenectomy.

A randomized prospective multicenter trial of pancreaticoduodenectomy with and without routine intraperitoneal drainage.

OBJECTIVE: To test by randomized prospective multicenter trial the hypothesis that pancreaticoduodenectomy (PD) without the use of intraperitoneal drainage does not increase the frequency or severity of complications. BACKGROUND: Some surgeons have abandoned the use of drains placed during pancreas resection. METHODS: We randomized 137 patients to PD with (n = 68, drain group) and without (n = 69, no-drain group) the use of intraperitoneal drainage and compared the safety of this approach and spectrum of complications between the 2 groups. RESULTS: There were no differences between drain and no-drain cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, baseline quality of life, or operative technique. PD without intraperitoneal drainage was associated with an increase in the number of complications per patient [1 (0-2) vs 2 (1-4), P = 0.029]; an increase in the number of patients who had at least 1 ≥grade 2 complication [35 (52%) vs 47 (68%), P = 0.047]; and a higher average complication severity [2 (0-2) vs 2 (1-3), P = 0.027]. PD without intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess (10% vs 25%, P = 0.027), severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. The Data Safety Monitoring Board stopped the study early because of an increase in mortality from 3% to 12% in the patients undergoing PD without intraperitoneal drainage. CONCLUSIONS: This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

Long-Term Survival, Toxicity Profile, and role of F-18 FDG PET/CT scan in Patients with Progressive Neuroendocrine Tumors Following Peptide Receptor Radionuclide Therapy with High Activity In-111 Pentetreotide.

AIM: To study the long term benefits, toxicity and survival rate in patients with neuroendocrine tumors receiving multiple cycles of high activity In-111 Pentetreotide therapy. Moreover, our secondary aim was to evaluate the value of F-18 FDG PET-CT scan as prognostic indicator in this group of patients. BACKGROUND: Neuroendocrine tumors are a heterogeneous group of malignancies which are usually metastatic at diagnosis. Standard chemotherapy in these patients is associated with appreciable adverse events and low effectiveness. Since 1990s, Peptide receptor radionuclide therapy (PRRT) with radio-labeled somatostatin analogues has been introduced as a new method of treatment in patients with unresectable and/or metastatic neuroendocrine tumors expressing high levels of Somatostatin receptors. METHODS: 112 patients with progressive disseminated and unresectable neuroendocrine tumor (stage III and stage IV) were enrolled in a non-randomized trial in an out-patient setting. High activity In-111 Pentetreotide (500 mCi (18.5 GBq) per cycle) was administered as an intravenous infusion over 3 hours and repeated therapy cycles every 9-12 weeks in eligible patients up to maximum of 4 cycles. Response to therapy was evaluated by clinical imaging using the RECIST criteria, metabolic criteria and patient's quality of life questionnaire. Dosimetry and biodistribution studies were also performed. Finally, Kaplan-Meier survival analysis was performed for patients followed for greater than 12 months. The relationship between pretreatment F-18 FDG PET-CT scan status and survival was determined by two-tailed Student's t-test in 42 patients who underwent pre-therapy PET scans. RESULTS: For an average of 25 (median 18.65) months following the therapy, patients were evaluated for any evidence of toxicity. No significant acute toxicity was observed in patients. Grade II or III hematological toxicity (7.6% of patients), liver toxicity (18.4%) and also grade I renal toxicity (6.1%) was observed in 92 evaluable patients. Radiological responses were evaluated for an average of 29 months following their last cycle of therapy and results were analyzed by the RECIST criteria. Majority (85%) of patients had stable disease (SD), partial response (PR) rate was 7.5% and progressive disease (PD) was observed in 7.5% of patients. The average survival was 24.67 months after 2 cycles of therapy, 30.53 months after 3 cycles of therapy and 30.19 months after 4 cycles of therapy. Of the 42 patients who had pretreatment PET-CT imaging, 31 patients had positive F-18 FDG scans (SUV > 2.5) with an average survival time of 18.9 months (range 1.4-45.8 months) and 11 patients had negative F-18 FDG scans (SUV ≤ 2.5) with an average survival time of 31.8 months (range 7.4-42.9 months). Survival times for FDG negative patients were significantly longer than those for FDG positive patients (p = 0.001 with 95% confidence). CONCLUSION: High activity In-111 therapy is a safe and effective therapy for patients with progressive disseminated neuroendocrine tumors. No major hematological, renal and hepatic toxicities were observed. There was an increase in survival time particularly in patients with lower degree of liver involvement as well as patients who received three or more cycles of therapy, as compared to historical data. Pre-treatment FDG status may be a predictor of survival following In-111 pentetreotide therapy.

Topically applied 2-octyl cyanoacrylate (Dermabond) for prevention of postoperative pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVE: We examined whether 2-octyl cyanoacrylate (Dermabond) topically applied to the pancreaticojejunostomy (PJ) anastomotic site after pancreaticoduodenectomy (PD) reduces the rate of postoperative pancreatic fistula (POPF). METHODS: Patients who underwent PD with duct-to-mucosa PJ were evaluated (n = 124). Outcome was compared between patients who received Dermabond (n = 75) after PD and historic patients who did not (n = 49). Risk factors for POPF were identified. RESULTS: Overall and clinically relevant rates of POPF were significantly lower in patients who received Dermabond than in patients who did not (2.6 % and 1.3 % vs. 22 % and 12 %, respectively; p = 0.001). In univariate analysis, pancreatic duct diameter ≤3 mm, low serum albumin level, and no Dermabond were independent risk factors for POPF; in multivariate analysis, no Dermabond was an independent risk factor for POPF. In patients with pancreatic duct diameter ≤3 mm, the rate of POPF was significantly lower in patients who received Dermabond than in patients who did not (3.5 % versus 36 %, respectively; p = 0.0001). Patients who received Dermabond had significantly shorter hospital stays and lower re-operation and re-admission rates. CONCLUSIONS: Topical application of Dermabond to the PJ anastomotic site after PD significantly reduced the rate of POPF, particularly in patients at risk.

Use of decellularized porcine liver for engineering humanized liver organ.

BACKGROUND: New bioartificial liver devices are needed to supplement the limited supply of organ donors available for patients with end-stage liver disease. Here, we report the results of a pilot study aimed at developing a humanized porcine liver by transplanting second trimester human fetal hepatocytes (Hfh) co-cultured with fetal stellate cells (Hfsc) into the decellularized matrix of a porcine liver. MATERIAL AND METHODS: Ischemic livers were removed from 19 Yorkshire swine. Liver decellularization was achieved by an anionic detergent (SDS). The decellularized matrix of three separate porcine liver matrices was seeded with 3.5 × 10(8) and 1 × 10(9) of Hfsc and Hfh, respectively, and perfused for 3, 7, and 13 d. The metabolic and synthetic activities of the engrafted cells were assessed during and after perfusion. RESULTS: Immunohistologic examination of the decellularized matrix showed removal of nuclear materials with intact architecture and preserved extracellular matrix (ECM) proteins. During perfusion of the recellularized matrices, measurement of metabolic parameters (i.e., oxygen concentration, glucose consumption, and lactate and urea production) indicated active metabolism. The average human albumin concentration was 29.48 ± 7.4 µg/mL. Immunohistochemical analysis revealed cell differentiation into mature hepatocytes. Moreover, 40% of the engrafted cells were actively proliferating, and less than 30% of cells were apoptotic. CONCLUSION: We showed that our decellularization protocol successfully removed the cellular components of porcine livers while preserving the native architecture and most ECM protein. We also demonstrated the ability of the decellularized matrix to support and induce phenotypic maturation of engrafted Hfh in a continuously perfused system.

Clinical value of plasma hepatocyte growth factor measurement for the diagnosis of periampullary cancer and prognosis after pancreaticoduodenectomy.

BACKGROUND: Previous studies suggest that serum hepatocyte growth factor (HGF) level may be a useful diagnostic and prognostic biomarker for various tumors. We investigated the utility of plasma HGF level measurements in diagnosing periampullary cancer (PAC). METHODS: Of the patients enrolled in this pilot study (n = 118), 57 had PAC, 21 had benign pancreatic tumor (BPT), 20 had chronic pancreatitis (CP), and 20 were healthy controls. Plasma HGF was measured with ELISA kits. It was measured again at 10 days and 1, 2, 3, 6, and 12 months after pancreaticoduodenectomy (PD). RESULTS: Plasma HGF levels were significantly higher in PAC patients than in BPT patients, CP patients, or healthy controls. When a cutoff value of 1,120 pg/ml was used, 48/57 (84%) patients with PAC were positive for elevated HGF, but only 6/20 (30%) of patients with CP and none of the controls or patients with BPT were positive for elevated HGF. After PD, HGF levels were significantly elevated at day 10. CONCLUSIONS: Plasma HGF level discriminates well between PAC and other, benign diseases. Therefore, HGF measurement could be a useful addition to the existing array of diagnostic tools for PAC pancreatic cancer. The higher postoperative value may reflect the stress of surgery.

Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-treat analysis.

In selected patients, locoregional therapy (LRT) has been successful in downstaging advanced hepatocellular carcinoma (HCC) so that the conventional criteria for liver transplantation (LT) can be met. However, the factors that predict successful treatment are largely unidentified. To determine these factors, we analyzed our experience with multimodal LRT in downstaging advanced HCC before LT in a retrospective cohort study. Thirty-two patients with advanced HCC exceeding conventional and expanded criteria for LT underwent therapy, but only those patients whose tumors were successfully downstaged were considered for LT. Eighteen patients (56%) had their tumors successfully downstaged; 14 patients (44%) did not. No intergroup differences existed with respect to patient characteristics or the types and number of treatments. However, mean alpha-fetoprotein levels were significantly higher in the non-downstaged group than in the downstaged group (P < 0.048), and significantly more patients in the non-downstaged group had infiltrative tumors (P = 0.0001). The median survival time was 42 and 7 months for the downstaged and non-downstaged groups, respectively (P = 0.0006). Fourteen patients (43.3%) underwent LT. After a median follow-up period of 35 months (range, 1.5-50 months) after LT, 2 patients (14.2%) developed tumor recurrence. The Kaplan-Meier survival rates after LT were 92% at 1 year and 75% at 2 years. The noninfiltrative expanding tumor type was the sole predictor of successful downstaging and improved outcome on univariate and multivariate analyses. Our study suggests that, in patients with advanced HCC, morphological characteristics of the tumor may predict a good response to downstaging and an improved outcome after LT.

Gastric radiation enteritis after intra-arterial yttrium-90 microsphere therapy for early stage hepatocellular carcinoma.

OBJECTIVES: As clinicians who treat hepatocellular carcinoma move yttrium-90 intra-arterial radiotherapy from the palliative setting to the treatment of patients with potentially curable early stage disease, more intense scrutiny of the safety of that procedure is warranted. To demonstrate the potential risks associated with this treatment, in the following case report, we describe a patient with early stage hepatocellular carcinoma who experienced severe toxicity from intra-arterial radiotherapy. MATERIALS AND METHODS: Screening studies in a 64-year-old Asian woman with a history of hepatitis C virus infection and cirrhosis identified a 3.5-cm well-differentiated hepatocellular carcinoma with no vascular invasion. After initial evaluation, the patient received treatment with intra-arterial radiotherapy. Four weeks after the conclusion of that therapy, she experienced nausea, vomiting, and weight loss. Upper endoscopy with biopsy identified antral gastritis and embolic microspheres in the submucosal layer of the gastric antrum. RESULTS: When she was subsequently referred for a liver transplant evaluation, her symptoms included failure to thrive and persistent weight loss. She was initially treated with feeding via a jejunostomy tube and ultimately received a liver transplant. However, 8 months after transplant she required an urgent gastrojejunostomy to bypass a progressive pyloric outlet obstruction. At the time of this writing, 1 year has elapsed since this patient received a liver transplant. No evidence of malignancy has been identified, but she remains partially dependent on tube feedings. CONCLUSIONS: This case highlights the potential risks associated with radioactive microsphere embolization in patients with hepatocellular carcinoma. Given the paucity of data regarding the efficacy of this therapy in treating early stage disease, the use of radioactive microsphere therapy in that patient population should be prospectively studied. To minimize the risk of complications, internationally approved consensus guidelines for the delivery of yttrium-90 should be followed.

Major liver resection for hepatocellular carcinoma in the morbidly obese: a proposed strategy to improve outcome.

BACKGROUND: Morbid obesity strongly predicts morbidity and mortality in surgical patients. However, obesity's impact on outcome after major liver resection is unknown. CASE PRESENTATION: We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2). Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection. CONCLUSION: To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts.

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

PURPOSE: To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. MATERIALS AND METHODS: Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. RESULTS: There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. CONCLUSION: (90)Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Complex liver resection for a large intrahepatic cholangiocarcinoma in a Jehovah's witness: a strategy to avoid transfusion.

Although morbidity and mortality after liver resection have improved over the last two decades, complex liver resections still require perioperative blood transfusions. In this report, we describe the use of a combined left trisegmentectomy and caudate lobectomy, along with resection of the inferior vena cava, to treat a large intrahepatic cholangiocarcinoma in a Jehovah's Witness. To our knowledge, this is the first report of major liver resection for a large malignant tumor in this patient population. We also discuss the perioperative strategy and surgical technique we used to minimize blood loss and avoid transfusion. This approach could be a safe alternative for use in all patients with complex liver tumor, regardless of their religious beliefs, to reduce the risks and cost associated with blood transfusion.