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Background: A significant proportion of patients with rectal cancer will present with synchronous metastasis at the time of diagnosis. Overall survival (OS) for these patients are highly variable and previous attempts to build predictive models often have low predictive power, with concordance indexes (c-index) less than 0.70.Methods: Using the National Cancer Database (2010-2014), we identified patients with synchronous metastatic rectal cancer. The data was split into a training dataset (diagnosis years 2010-2012), which was used to build the machine learning model, and a testing dataset (diagnosis years 2013-2014), which was used to externally validate the model. A nomogram predicting 3-year OS was created using Cox proportional hazard regression with lasso penalization. Predictors were selected based on clinical significance and availability in NCDB. Performance of the machine learning model was assessed by c-index.Results: A total of 4098 and 3107 patients were used to construct and validate the nomogram, respectively. Internally validated c-indexes at 1, 2, and 3 years were 0.816 (95% CI 0.813-0.818), 0.789 (95% CI 0.786-0.790), and 0.778 (95% CI 0.775-0.780), respectively. External validated c-indexes at 1, 2, and 3 years were 0.811, 0.779, and 0.778, respectively.Conclusions: There is wide variability in the OS for patients with metastatic rectal cancer, making accurate predictions difficult. However, using machine learning techniques, more accurate models can be built. This will aid patients and clinicians in setting expectations and making clinical decisions in this group of challenging patients. [ABSTRACT FROM AUTHOR]

Background: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation.Methods: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers.Results: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients.Conclusions: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed. [ABSTRACT FROM AUTHOR]

Introduction: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. Methods: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results: During the median follow up duration of 31 months (range 1–208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34–3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01–2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10–2.25; P = .04), and tumor size ≥5 cm (HR, 1.84; 95% CI, 1.28–2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. Conclusion: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence. [Copyright &y& Elsevier]

Background: Although standard of care after most abdominal surgeries, post-operative pharmacologic thromboprophylaxis after major hepatectomy is commonly withheld due to bleeding risks. The objective of this retrospective study is to evaluate the benefits and risks of post-operative pharmacologic thromboprophylaxis after major hepatectomy at two high volume academic centers.Methods: Demographics, clinicopathologic data, treatments, and post-operative outcomes from patients who underwent major hepatectomy were reviewed.Results: From 2005 to 2010, 419 patients underwent major hepatectomy; 275 (65.6%) were treated with pharmacologicthromboprophylaxis beginning a median of 1 day after resection. Post-operative symptomatic venous thromboembolism (VTE) occurred in 15 (3.6%) patients. Patients treated with pharmacologic thromboprophylaxis had lower rates of symptomatic VTE (2.2% vs. 6.3%, p = 0.03) and post-operative red blood cell (RBC) transfusion (16.7% vs. 26.4%, p = 0.02) with similar rates of overall RBC transfusion (35.0% vs. 30.6%, p = 0.36) compared to untreated patients. Specifically, isolated deep venous thrombosis (0% vs. 2.1%, p = 0.04) and pulmonary embolism (2.2% vs. 4.2%, p = 0.35) occurred less often in treated patients. Analysis of demographics, clinicopathologic data, and treatment factors revealed that pharmacologic thromboprophylaxis was the only variable associated with post-operative VTE.Conclusions: Post-operative pharmacologic thromboprophylaxis lowers the incidence of symptomatic VTE after major hepatectomy without increasing the rate of RBC transfusion. [ABSTRACT FROM AUTHOR]

Introduction: The lack of accurate markers makes preoperative differentiation between pancreatic cancer and non-malignant head lesions clinically challenging. In this study, we investigated the incidence of benign disease in patients that underwent resection for presumed pancreatic cancer diagnosed by EUS and EUS-guided FNA.Methods: Medical records of consecutive patients who underwent pancreaticoduodenectomy at Duke University were reviewed. Demographics, clinicopathologic characteristics, preoperative imaging, EUS, EUS-guided FNA, and postoperative outcomes were analyzed.Results: Seven percent of the total 494 patients studied were found to have benign disease on postoperative pathology. Fifty-nine percent of these patients with benign disease underwent preoperative EUS. EUS was positive for a head mass in 70%, demonstrated enlarged lymph nodes in 27%, and showed signs concerning for vascular invasion in 13%. FNA was suspicious or indeterminate for cancer in 63% of patients. Postoperative complications occurred in 47% and one patient died after surgery. The overall pancreatic leak rate was 15%.Conclusions: Even with aggressive use of preoperative evaluation, there is still a small subset of patients where malignancy cannot be excluded without pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

Introduction: Proposed criteria for resection of pancreatic cystic lesions have included symptoms, size (>3 cm), and suspicious features by endoscopic ultrasound (EUS). The objective of this study was to evaluate risk factors for malignancy in a large series of patients undergoing resection of suspected pancreatic cystic neoplasms.Methods: Medical records of patients selected for resection of pancreatic cystic lesions at Duke University Medical Center from 2000 to 2008 were reviewed. Lesions with solid components on cross-sectional imaging were excluded. Malignancy was defined as invasive or in situ carcinoma.Results: After review, 101 patients were confirmed to have undergone resection for suspected cystic neoplasms of the pancreas. Preoperative EUS was performed in 71 patients. Sixteen patients (16%) had malignant lesions (preoperative size 1.5-5.9 cm). There was no clear association between size and malignancy. Male gender, biliary ductal dilatation (BDD), pancreatic ductal dilatation (PDD), and suspicious cytology (but not age, symptoms, or size) were associated with increased risk of malignancy. When factors available for all patients were incorporated into a multivariate model, only BDD and PDD were independent risk factors for malignancy. Only one patient with malignancy had neither BDD nor PDD but did have solid components by EUS.Conclusions: In patients selected for resection, size was not an independent risk factor for malignancy. While size might be appropriate for stratification of asymptomatic patients with simple cysts, size should not be used as a selection criterion for patients who have cysts with solid components or with associated BDD or PDD. [ABSTRACT FROM AUTHOR]

Background: Few studies identifying variables associated with prognosis after resection of colorectal liver metastases (CLM) account for treatment with multiagent chemotherapy (fluoropyrmidines with irinotecan, oxaliplatin, bevacizumab, and/or cetuximab). The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM.Methods: Demographics, clinicopathologic tumor characteristics, treatments, and long-term outcomes were reviewed.Results: From 1996 to 2006, 230 patients underwent resection of CLM. Treatment strategies before and after resection included fluoropyrimidine monotherapy (n = 34 and n = 39), multiagent chemotherapy (n = 81 and n = 73), and observation (n = 115 and n = 118). Prehepatectomy treatment strategy was not associated with overall survival. Actuarial 4-year survival was 63%, 39%, and 40% for patients treated with multiagent chemotherapy, fluoropyrimidine monotherapy, and observation after hepatectomy, p = 0.06. Posthepatectomy multiagent chemotherapy (p = 0.04, HR 0.52 [0.27-1.03]), duration of posthepatectomy chemotherapy treatment of 2 months or longer (p = 0.05, HR 0.49 [0.25-0.99]), carcino-embryonic antigen level >10 ng/mL (p = 0.03, HR 2.09, 95% CI [1.32-3.32]), and node positive primary tumor (p = 0.002, HR 1.79 [1.06-3.02]) were associated with overall survival in multivariate analysis.Conclusions: The association of posthepatectomy multiagent chemotherapy with overall survival in this retrospective study indicates the need for prospective randomized trials comparing multiagent chemotherapy and fluoropyrimidine monotherapy for CLM. [ABSTRACT FROM AUTHOR]

Most patients with familial adenomatous polyposis (FAP) develop disease in the duodenum. The duodenal lesions mostly occur in the periampullary region, but some patients develop diffuse polyposis involving all parts of the duodenum. These neoplastic polpys have malignant potential, and thus warrant surveillance and timely intervention. We reviewed our experience with management of FAP over a 10-year period, focusing on patients who had diffuse polyposis of the duodenum and their subsequent management. Three patients with FAP had diffuse duodenal involvement, documented by upper gastrointestinal endoscopy. Neoplasia was confirmed by endoscopic biopsy, but no patients had histologic evidence of carcinoma. The patients underwent resection of the entire duodenum from the pylorus to the ligament of Treitz with preservation of the pancreas. Our surgical technique is described. One patient had a postoperative wound infection and one patient had a biliary leak that resolved with closed suction drainage for 5 days. Long-term follow-up in these patients revealed excellent functional status. One patient had polyp recurrence in the jejunum at 5-year follow-up, but no patients have developed adenocarcinoma. We conclude that patients with duodenal polyps associated with FAP may be safely and effectively treated by pancreas-preserving duodenectomy. ( J Gastrointest Surg 2002;6:82–87.) [Copyright &y& Elsevier]

An introduction to the journal is presented in which the editor discusses the roles of systemic therapies in patients with unresectable and resectable hepatic metastases.

Background Hepatic and pancreatic surgery is rarely performed in patients with end-stage renal disease ( ESRD). The present authors used a national clinical database to characterize outcomes and perioperative risk in ESRD patients who require hepatic or pancreatic resection. Methods The 2005-2011 National Surgical Quality Improvement Program database was queried for all patients undergoing hepatic or pancreatic resection. Patients were classified by the presence or absence of ESRD. The independent effects of ESRD on outcomes were assessed after propensity score adjustment and multivariable logistic regression. Results Of the 27 376 patients submitted to hepatic or pancreatic procedures identified in the database, 101 patients were found to have preoperative ESRD. Patients with ESRD experienced perioperative mortality at a rate similar to that in those without ESRD (5.0% versus 2.3%; P = 0.08). After risk adjustment, the presence of ESRD was associated with three-fold higher odds of postoperative sepsis (adjusted odds ratio: 2.98, P = 0.014), but no significant differences in mortality or major complication rates. Conclusions Hepatic and pancreatic resections can be performed safely in selected patients with ESRD. These patients may have an increased risk for the development of postoperative sepsis. Further study is needed to characterize modifiable risk factors that impact outcomes in patients with ESRD who require hepatic or pancreatic resection. [ABSTRACT FROM AUTHOR]

Background: The goal of our study was to determine the temporal trends in provider volume for liver resection procedures. Study Design: The Nationwide Inpatient Sample database for 1988 through 2003 was used to determine temporal trends in hospital and surgeon volume of liver resection procedures. We also examined whether these trends in provider volume were associated with any changes in postoperative outcomes or in patients'' access to high-volume providers. Results: Regionalization of liver resection procedures to high-volume surgeons and hospitals has been occurring since 1988 and, in the most recent time period assessed, 25.8% of patients underwent hepatic resection by high-volume surgeons (≥ 17 procedures per year) and 29.9% of patients underwent resection in high-volume hospitals (≥ 45 procedures per year). Unadjusted mortality data suggest that these trends might be associated with a strengthening of the inverse relationship between hospital volume of hepatic resection and postoperative mortality and with an increasing disparity for some patient populations in use of high-volume hospitals. Conclusions: Regionalization of liver resections is occurring at both the level of the individual surgeon and the hospitals where these procedures are performed. These trends in provider volume might be associated with increasing discrepancies in outcomes and patient demographics among different volume categories of hospitals. [Copyright &y& Elsevier]

Introduction The drive to improve outcomes and the inevitability of mandated public reporting necessitate uniform documentation and accurate databases. The reporting of wound classification in patients undergoing hepato-pancreatico-biliary ( HPB) surgery and the impact of inconsistencies on quality metrics were investigated. Methods The 2005-2011 National Surgical Quality Improvement Program ( NSQIP) participant use file was interrogated to identify patients undergoing HPB resections. The effect of wound classification on post-operative surgical site infection ( SSI) rates was determined through logistic regression. The impact of variations in wound classification reporting on perceived outcomes was modelled by simulating observed-to-expected ( O/E) ratios for SSI. Results In total, 27 376 patients were identified with significant heterogeneity in wound classification. In spite of clear guidelines prompting at least 'clean-contaminated' designation for HPB resections, 8% of all cases were coded as 'clean'. Contaminated [adjusted odds ratio ( AOR): 1.39, P = 0.001] and dirty ( AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas clean-contaminated were not ( P = 0.99). O/E ratios were highly sensitive to modest changes in wound classification. Conclusions Perceived performance is affected by heterogeneous reporting of wound classification. As institutions work to improve outcomes and prepare for public reporting, it is imperative that all adhere to consistent reporting practices to provide accurate and reproducible outcomes. [ABSTRACT FROM AUTHOR]

Background: Despite the rising incidence of hepatocellular carcinoma (HCC), challenges and controversy persist in optimizing treatment. As recent randomized trials suggest that ablation can have oncologic equivalence compared with resection for early HCC, the relative morbidity of the 2 approaches is a central issue in treatment decisions. Although excellent contemporary perioperative outcomes have been reported by a few hepatobiliary units, it is not clear that they can be replicated in broader practice. Our objective was to help inform this treatment dilemma by defining perioperative outcomes in a broader set of patients as represented in NSQIP-participating institutions. Study Design: Mortality and morbidity data were extracted from the 2005–2010 NSQIP Participant Use Data Files based on Current Procedural Terminology (hepatectomy and ablation) and ICD-9 (HCC). Perioperative outcomes were reviewed, and factors associated with morbidity and mortality were identified with multivariable logistic regression. Results: Eight hundred and thirty-seven (52%) underwent minor hepatectomy, 444 (28%) underwent major hepatectomy, and 323 (20%) underwent surgical ablation. Mortality rates were 3.4% for minor hepatectomy, 3.7% for ablation, and 8.3% for major hepatectomy (p < 0.01). Major complication rates were 21.3% for minor hepatectomy, 9.3% for ablation, and 35.1% for major hepatectomy (p < 0.01). When controlling for confounders, ablation was associated with decreased mortality (adjusted odds ratio = 0.20; 95% CI, 0.04–0.97; p = 0.046) and major complications (adjusted odds ratio = 0.34; 95% CI, 0.22–0.52; p < 0.001). Conclusions: Exceedingly high complication rates after major hepatectomy for HCC exist in the broader NSQIP treatment environment. These data strongly support the use of parenchymal-sparing minor resections or ablation over major hepatectomy for early HCC when feasible. [Copyright &y& Elsevier]

Background: Although the perioperative mortality from hepatic resection has improved considerably, this procedure is still associated with substantial morbidity and resource use. The goal of this investigation was to characterize the incidence, patterns, and risk factors for early reoperation and readmission after hepatectomy. Study Design: Perioperative outcomes of 1,281 patients undergoing hepatic resection at an academic center from 1996 to 2009 were analyzed. The indications for early reoperation and readmission (90 days) were reviewed. Multivariate logistic regression analysis was performed to determine variables associated with reoperation and readmission. A scoring system was generated to predict the need for readmission after hepatectomy. Results: Eighty-seven patients (6.8%) required reoperation. The perioperative mortality in patients requiring reoperation was significantly higher than for those not requiring reoperation (23.0% vs 3.4%; p < 0.001). Variables associated with reoperation included male sex, performance of concomitant major nonhepatic procedures, and greater intraoperative blood loss. One hundred and eighty-four patients (14.4%) required readmission. Variables associated with readmission included major hepatectomy, development of major postoperative complications, and index hospitalization >7 days. A Readmission Prediction Score ranging from 0 to 4 was generated and directly correlated with need for readmission. Conclusions: In the current era of hepatic surgery, early reoperation and readmission remain relatively frequent. As we care for patients who are increasingly receiving regionalized care far from home, we must be mindful of patients at increased risk for readmission. The development of strategies to minimize the complications that necessitate reoperation and readmission is critical to improving patient care. [ABSTRACT FROM AUTHOR]

Background: Although a concomitant diaphragm resection might be required at the time of hepatectomy to achieve tumor-free surgical margins, studies addressing its effect on postoperative morbidity and mortality have been inconclusive. The objective of this study was to determine whether the need for diaphragm resection at the time of hepatectomy truly increases 30-day morbidity or mortality using data from the American College of Surgeons National Surgical Quality Improvement Program. Study Design: Data were obtained from the 2005-2010 American College of Surgeons National Surgical Quality Improvement Program Participant User Files based on CPT coding. All patients undergoing a simultaneous liver and diaphragm resection were propensity-matched to a subset of liver resection patients not undergoing a diaphragm resection. The main outcomes measures were 30-day mortality and morbidity. Results: One hundred and ninety-two patients who underwent combined liver and diaphragm resection were matched to 192 patients treated with liver resection alone. The need for concomitant diaphragm resection was associated with a higher overall complication rate (38.54% vs 28.65%; p = 0.048), major complication rate (33.33% vs 23.44%; p = 0.030), and respiratory complication rate (14.06% vs 7.81%; p = 0.058). Postoperative mortality was similar between groups. Combined diaphragm and liver resection was also associated with longer operative times (median 311 minutes vs 247.5 minutes; p < 0.001), higher rates of intraoperative packed RBC transfusion (33.33% vs 23.44%; p = 0.037), and a longer length of hospitalization (median 7 vs 6 days; p = 0.002). Conclusions: The results of this study, when taken into account with those reported previously, suggest that the need for diaphragm resection at time of hepatectomy increases postoperative morbidity but not mortality. [ABSTRACT FROM AUTHOR]

Background: Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases. Study Design: A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. Results: There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003). Conclusions: Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined. [Copyright &y& Elsevier]

Background: While commonly used to describe liver resections at risk for post-operative complications, no standard definition of 'major hepatectomy' exists. The objective of the present retrospective study is to specify the extent of hepatic resection that should describe a major hepatectomy. Methods: Demographics, diagnoses, surgical treatments and outcomes from patients who underwent a liver resection at two high-volume centres were reviewed. Results: From 2002 to 2009, 1670 patients underwent a hepatic resection. Post-operative mortality and severe, overall and hepatic-related morbidity occurred in 4.4%, 29.7%, 41.6% and 19.3% of all patients. Mortality (7.4% vs. 2.7% vs. 2.6%) and severe (36.7% vs. 24.7% vs. 24.1%), overall (49.3% vs. 40.6% vs. 35.9%) and hepatic-related (25.6% vs. 16.4% vs. 15.2%) morbidity were more common after resection of four or more liver segments compared with after three or after two or fewer segments (all P < 0.001). There were no significant differences in any post-operative outcome after resection of three and two or fewer segments (all P > 0.05). On multivariable analysis, resection of four or more liver segments was independently associated with post-operative mortality and severe, overall, and hepatic-related morbidity (all P < 0.01). Conclusions: A major hepatectomy should be defined as resection of four or more liver segments. [ABSTRACT FROM AUTHOR]

Background: Because of the aging United States population, increase in overall life expectancy, and rising incidence of hepatobiliary tumors, more elderly patients are considered for hepatic resection. The objective of this study was to assess the influence of age on postoperative outcomes after major hepatectomy among a contemporary cohort from 2 high volume centers. Study Design: Demographics, diagnoses, surgical treatments, and postoperative outcomes of patients who underwent major hepatic resection were reviewed. Results: There were 856 patients who underwent major hepatectomy (resection of 3 or more segments) from 2002 to 2009. Postoperative mortality and morbidity occurred in 53 (6.2%) and 403 (47.1%) patients, respectively. Increasing age was independently associated with postoperative mortality (p = 0.0345). Each 1-year and 10-year increase in age resulted in an odds ratio of mortality after major hepatic resection of 1.036 (95% CI [1.003-1.071]) and 1.426 (95% CI [1.026-1.982]), respectively. This relationship was independent of American Society of Anesthesiology (ASA) score. Increasing age was associated with postoperative sepsis (p = 0.0224, odds ratio for each year 1.025 [range 1.003 to 1.048]) after major hepatic resection, but not overall postoperative morbidity. Conclusions: In the contemporary era, increasing age is independently associated with postoperative mortality after major hepatic resection at high volume academic centers. [Copyright &y& Elsevier]

Introduction: Nomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC).hpb_106 592..599 Methods: An external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram. Results: After median follow-up of 30.4 months (range 0.33-150), Kaplan--Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram- predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n = 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P = 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients. Conclusions: The CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatocellular carcinoma (HCC) most often occurs within hepatocellular adenomas (HCAs) in glycogen storage disease Ia (GSD Ia) patients. The objective of this retrospective study is to assess outcomes after liver transplantation (LT) for GSD Ia where the principal indication for transplantation was prevention of HCC. Methods: Petitions to the United Network for Organ Sharing region 11 review board for additional model for end-stage liver disease listing points were made on behalf of GSD Ia patients. Demographics, pre-operative comorbidity, and outcomes for GSD Ia patients who underwent LT were reviewed. Results: Between 2004 and 2006, five GSD Ia patients underwent LT. Multiple HCAs with focal hemorrhage and/or necrosis but without histological evidence of malignancy were identified in all explanted specimens. Four of five patients had complications after LT, including cytomegalovirus (CMV) infections and steroid responsive allograft rejection. Hemoglobin levels and serum triglyceride, total cholesterol, blood glucose, and lactic acid concentrations improved in all patients after LT. Corn starch feeding was not required in any patient after LT. Renal function worsened in three patients despite modifications to primary immunosuppressive medications. All patients are alive at last follow-up (range 25–48 months) and all post-transplant complications have resolved. Conclusions: By removing all possible adenomatous tissue and reversing the underlying hepatic enzymatic deficiency, LT provides definitive prevention against HCC and correction of most metabolic derangements in GSD Ia patients. Renal dysfunction secondary to GSD Ia persists—underscoring the need for further studies to better understand the mechanisms of renal dysfunction in these patients. [Copyright &y& Elsevier]

Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age ≤60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic therapy. [Copyright &y& Elsevier]

Background: We wanted to determine whether current levels of fellowship training in hepato-pancreato-biliary (HPB) surgery will be sufficient to meet demand for HPB procedures in 2020. Study Design: The Nationwide Inpatient Sample database for 1988 through 2003 was used to construct projections for the number of HPB procedures that will be performed in the US each year through 2020. Available workforce literature was also used to generate estimates of current and future supply of HPB subspecialists. These demand and supply estimates were then used to construct sensitivity analyses of the mean number of HPB procedures per subspecialist in 2020, depending on the degree of regionalization that exists and the number of fellowship-trained subspecialists needed to train each year to meet projected demand for HPB procedures in 2020. Results: An estimated 16,800 HPB procedures will be performed in 2020, representing a 25% increase during the next 15 years. We estimate that 28 fellowship-trained HPB subspecialists will enter the workforce each year. If half of all HPB procedures are performed by HPB subspecialists in 2020, then the average subspecialist will perform only 14 such procedures that year. If high-volume HPB surgery is defined as 40 procedures per year, and 50% of HPB procedures are performed by high-volume surgeons in 2020, then only 15 fellows need to be trained in HPB surgery each year to meet demand in 2020. Conclusions: Current levels of fellowship training will result in an excess of HPB subspecialists in 2020. [Copyright &y& Elsevier]

Background: Although commonly used in combination with irinotecan or oxaliplatin (iri/oxal) for treatment of colorectal liver metastases before extirpation, the effects of preoperative bevacizumab on surgical outcomes are not established. The objective of this retrospective study was to determine if addition of bevacizumab to iri/oxal preoperative chemotherapy increases morbidity after hepatic resection.Study Design: We compared demographics, clinicopathologic data, treatments, and postoperative outcomes between patients given preoperative iri/oxal with and without bevacizumab and patients who underwent hepatic resection within and after 8 weeks from the last dose of bevacizumab.Results: From 1996 to 2006, 96 patients were treated with preoperative iri/oxal; 39 (40.6%) received concurrent bevacizumab. Preoperative bevacizumab treatment was associated with less blood loss (median 425 mL versus 600 mL, p=0.01) and lower RBC transfusion rates (43.9% versus 23.1%, p=0.06) after partial hepatectomy on univariable analysis. Only age>or=70 years (hazard ratio=8.52, 95% CI [2.00 to 36.45]) and concurrent extrahepatic procedures (hazard ratio=4.12, 95% CI [1.49 to 11.39]) independently predicted RBC transfusion and overall complications, respectively. There were no differences in overall (43.6% versus 38.6%), severe (28.2% versus 24.6%), hepatic (17.9% versus 26.3%), wound (10.3% versus 7%), or thromboembolic or bleeding (2.6% versus 5.3%) complications (all p > 0.05). For patients treated with iri/oxal and bevacizumab, overall complications were more common when resection was performed within 8 weeks after the last bevacizumab dose (62.5% versus 30.4%), but this difference was not statistically significant (p=0.06).Conclusions: If discontinued at least 8 weeks before hepatic resection, addition of bevacizumab to preoperative iri/oxal does not increase morbidity after hepatic resection. [ABSTRACT FROM AUTHOR]

Due to the prevalence of tumor chemoresistance, the clinical response of advanced non-small cell lung cancer (NSCLC) to chemotherapy is poor. We suppressed tumor resistance to doxorubicin (Dox) in A549 cells, a human NSCLC cell line, both in vitro and in vivo in a lung tumor xenograft model, using a novel adenoviral expression system to deliver an RNA aptamer (A-p50) that specifically inhibits nuclear factor-κB (NF-κB) activation. By achieving selective, targeted, and early inhibition of NF-κB activity, we demonstrate that NF-κB plays a critical role in Dox-induced chemoresistance by regulating genes involved in proliferation (Ki-67), response to DNA damage (GADD153), antiapoptosis (Bcl-XL), and pH regulation (CA9). This Dox-induced NF-κB activation and subsequent chemoresistance is dependent on expression of p53. We also demonstrate that NF-κB promotes angiogenesis in the presence of Dox via the hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway, revealing a previously unknown mechanism of NSCLC resistance to Dox. These studies provide important insights into the mechanisms of Dox-induced chemoresistance, and they demonstrate a novel, effective, and clinically practical strategy for interfering with these processes.Molecular Therapy (2007) 16 1, 66–73. doi:10.1038/sj.mt.6300320 [ABSTRACT FROM AUTHOR]

Purpose: To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT). Methods and Materials: This was a retrospective analysis of all patients undergoing potentially curative therapy for adenocarcinoma of the duodenum at Duke University Medical Center and affiliated hospitals between 1975 and 2005. Overall survival (OS), disease-free survival (DFS), and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis evaluated the effect of CT-RT on clinical endpoints. Results: Thirty-two patients were identified (23 M, 9 F). Median age was 60 years (range, 32–77 years). Surgery alone was performed in 16 patients. An additional 16 patients received either preoperative (n = 11) or postoperative (n = 5) CT-RT. Median RT dose was 50.4 Gy (range, 12.6–54 Gy). All patients treated with RT also received concurrent 5-fluorouracil-based CT. Two patients treated preoperatively had a pathologic complete response (18%), and none had involved lymph nodes at resection. Five-year OS, DFS, and LC for the entire group were 48%, 47%, and 55%, respectively. Five-year survival did not differ between patients receiving CT-RT vs. surgery alone (57% vs. 44%, p = 0.42). However, in patients undergoing R0 resection, CT-RT appeared to improve OS (5-year 83% vs. 53%, p = 0.07). Conclusions: Local failure after surgery alone is high. Given the patterns of relapse with surgery alone and favorable outcomes in patients undergoing complete resection with CT-RT, the use of CT-RT in selected patients should be considered. [Copyright &y& Elsevier]

Background/Aims: Because dietary modifications have prolonged the life expectancy of patients with glycogen storage disease type Ia (GSD Ia), the incidence of hepatocellular adenoma (HCA) to carcinoma (HCC) transformation is increasing. The objective of this retrospective study is to assess the safety and effectiveness of HCA resection in GSD Ia patients. Methods: Clinicopathologic, peri-operative, and long-term data were reviewed from patients who underwent HCA resection. Comparisons were made with Fisher’s exact, Mann–Whitney U, and log-rank tests; survival was estimated with Kaplan–Meier analysis. Results: From 1998 to 2006, 38 patients underwent HCA resection. Seven (22%) had GSD Ia. Post-operative mortality occurred in one GSD Ia patient. GSD Ia patients had greater morbidity (86% vs. 20%) and shorter time to adenoma progression (median 23 months vs. not yet reached) after partial hepatectomy compared to the general population (p <0.05). Six GSD Ia patients had no evidence of HCC and recovered after resection without long-term morbidity. Three GSD Ia patients underwent liver transplantation 77, 32, and 23 months after adenoma resection. Conclusions: Despite substantial morbidity, partial hepatectomy is feasible in GSD Ia patients and is an effective intermediate step in the prevention of HCC until definitive treatment with liver transplantation. [Copyright &y& Elsevier]

Abstract: Background: Although radical cholecystectomy is the standard of care for gallbladder cancers that invade perimuscular connective tissue or perforate visceral peritoneum, the role of extended right hepatectomy in achieving negative resection margins is not clear. Methods: Clinicopathologic, perioperative, and long-term outcome data were reviewed from patients who underwent hepatic resection for gallbladder cancer. Results: From 1995 to 2005, 22 consecutive patients underwent hepatic resection for gallbladder cancer, and 11 underwent extended hepatectomy. Negative resection margins were achieved in all patients. There were no significant differences in postoperative morbidity, mortality, and long-term survival after extended and minor hepatectomy. T3 tumors negatively predicted overall and recurrence-free survival. Comments: Extended hepatectomy achieves negative resection margins for patients with gallbladder cancer and is associated with acceptable morbidity and long-term survival. [Copyright &y& Elsevier]

Background: To establish a reliable definition of postoperative hepatic insufficiency (PHI) in noncirrhotic patients undergoing major hepatectomy. No standard definition of PHI has been established, but one is essential for meaningful comparison of outcomes data across studies. Methods: Data from 1,059 noncirrhotic patients who underwent major hepatectomy (3 or more liver segments) at 3 centers from 1995 to 2005 were analyzed. Receiver operating characteristics (ROC) analysis of peak postoperative bilirubin (PeakBil) and international normalized ratio (PeakINR) were used to define PHI. Results: A total of 669 patients (63%) underwent resection of 3 to 4 liver segments; 390 (37%) underwent resection of 5 or more segments. Complications occurred in 453 (43%). The 90-day all-cause mortality rate was 4.7%, which is 47% higher than the 30-day rate (3.2%). Twenty (1.9%) patients died of causes unrelated to the liver. Of the remaining 1,039 patients, 30 (2.8%) died a median 36 days from liver-related causes (liver failure with or without multiorgan failure). ROC analysis revealed cut-offs that predict liver-related death are PeakBil 7.0 mg/dL (area under the curve 0.982; sensitivity 93.3%; specificity 94.3%) and PeakINR 2.0 (area under the curve 0.846; sensitivity 76.7%; specificity 82.0%). PeakBil > 7.0 mg/dL was the most powerful predictor of any (odds ratio [OR] = 83.3) or major complication (OR = 10.0), 90-day mortality (OR = 10.8), and 90-day liver-related mortality (OR = 250) (all p < 0.0001). Conclusions: PHI defined as PeakBil > 7.0 mg/dL accurately predicts liver-related death and worse outcomes after major hepatectomy. Standardized reporting of complications, PHI, and 90-day mortality is essential to accurately determine the risk of major hepatectomy and to compare outcomes data. [Copyright &y& Elsevier]

Background: Although established for metastatic colorectal (CR) and neuroendocrine (NE) malignancies, the role of partial hepatectomy in management of metastases from other primaries (NCRNE) is not well-defined. Study design: The objective of this retrospective study is to compare outcomes after partial hepatectomy for NCRNE, NE, and CR metastases and to identify factors associated with longterm survival for patients with NCRNE diseases. Tumor characteristics, treatments, and outcomes of 360 consecutive patients undergoing resection of NCRNE (n = 82), CR (n = 245), and NE (n = 33) hepatic metastases from 1995 to 2005 were analyzed. NCRNE tumors included breast (n = 20), sarcomas (n = 19), genitourinary (n = 18), melanoma (n = 11), and other (n = 14) cancers. The start date for followup and survival analyses was the date of partial hepatectomy. Results: For patients with NCRNE, CR, and NE tumors, there were no marked differences in postoperative mortality (4%, 4%, and 9%) or complication (30%, 42%, and 42%) rates. Median overall survival was longest for NE patients (not yet reached) versus NCRNE and CR (both 44 months) patients (p < 0.05, log-rank test). NCRNE patients had shorter disease-free survival than CR counterparts (13 versus 16 months), p < 0.05 (log-rank test). After median followup of 59 months for NCRNE patients, actuarial 5-year overall and disease-free survival was 37% and 16%, respectively, with 15 5-year survivors. Multivariable analysis suggests that interval from discovery of liver metastases to resection > 6 months (p = 0.08) and administration of chemoradiotherapy after resection (p = 0.06) might be associated with improved overall survival. Conclusions: In selected patients, resection of NCRNE liver metastases can be done safely with survival similar to CR metastases. Delay of liver resection for at least 6 months and treatment with chemoradiotherapy after resection might be associated with improved longterm survival after partial hepatectomy. [Copyright &y& Elsevier]

Purpose: Primary adenocarcinoma of the gallbladder is a rare malignancy. To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken. Methods and Materials: Twenty-two patients with primary and nonmetastatic gallbladder cancer were treated with radiation therapy after surgical resection. Median radiation dose was 45 Gy. Eighteen patients received concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in all patients and 3.9 years in survivors. Results: The 5-year actuarial overall survival, disease-free survival, metastases-free survival, and local-regional control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median survival for all patients was 1.9 years. Conclusion: Our series suggests that an approach of radical resection followed by external-beam radiation therapy with radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma of the gallbladder may improve survival. This regimen should be considered in patients with resectable gallbladder carcinoma. [Copyright &y& Elsevier]