Tumor Biology Impacts Survival in Surgically Managed Primary Hepatic Vascular Malignancies.

BACKGROUND: Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database. MATERIALS AND METHODS: In a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified. RESULTS: Three hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P< 0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival. CONCLUSIONS: In this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

Non-home Discharge and Prolonged Length of Stay After Cytoreductive Surgery and HIPEC.

BACKGROUND: Predictive models for nonhome discharge (NHD) have been proposed in major surgical specialties. The rates and risk factors associated with NHD and prolonged length of stay (PLOS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have not been evaluated. The aim of this study is to identify risk factors for NHD and PLOS after CRS/HIPEC in a national cohort of patients. MATERIALS AND METHODS: CRS/HIPEC cases were identified from the National Surgical Quality Improvement Program 2011-2012 data set. Patients with an NHD or PLOS (>30 d) were compared with a group of patients discharged to home within 30 d. Univariate analysis was used to compare patient characteristics, operative variables, and postoperative complications among both groups. Multivariate regression analysis was used to identify independent predictors of NHD and PLOS. RESULTS: Five hundred fifty-six patients undergoing CRS/HIPEC were identified, of which 44 (7.9%) were not discharged to home within 30 d. The rate of NHD and PLOS in this cohort was 4.1% and 3.7%, respectively. Multivariate analysis identified age ≥65 y, pre-op albumin <3.0 g/dL, and having a multivisceral resection as independent predictors of NHD/PLOS. If all three predictors are met preoperatively, the probability of NHD/PLOS was calculated to be 30.2%. CONCLUSIONS: The main risk factors for NHD/PLOS after CRS/HIPEC were advanced age, hypoalbuminemia, and multivisceral resection. Adequate identification of these risk factors may facilitate preoperative discussion with patients, and improve discharge planning and resource utilization.

Statistical justification of expansion cohorts in phase 1 cancer trials.

BACKGROUND: Phase I cancer trials increasingly incorporate dose-expansion cohorts (DECs), reflecting a growing demand to acquire more information about investigational drugs. Protocols commonly fail to provide a sample-size justification or analysis plan for the DEC. In this study, we develop a statistical framework for the design of DECs. METHODS: We assume the maximum tolerated dose (MTD) for the investigational drug has been identified in the dose-escalation stage of the trial. We use the 80% lower confidence bound and the 90% upper confidence bound for the response and toxicity rates, respectively, as decision thresholds for the dose-expansion stage. We calculate the operating characteristics with reference to prespecified minimum effective response rates and maximum safe DLT rates. RESULTS: We apply our framework to specify a system of DEC plans. The design comprises three components: 1) the number of subjects enrolled at the MTD, 2) the minimum number of responses necessary to indicate provisional drug efficacy, and 3) the maximum number of dose-limiting toxicities (DLTs) permitted to indicate drug safety. We demonstrate our method in an application to a cancer immunotherapy trial. CONCLUSIONS: Our simple and practical tool enables creation of DEC designs that appropriately address the safety and efficacy objectives of the trial.

Adoption of evidence-based novel therapies in the treatment of gastric cancer: A national observational study.

BACKGROUND: The adoption of novel and effective gastric cancer therapies into general clinical practice has crucial implications for patient outcomes. The current study explored trends in treatment use and overall survival in patients with gastric cancer in the United States. METHODS: Patients with adenocarcinoma of the gastric cardia and noncardia were identified in the National Cancer Data Base between 2006 and 2014. Tumor stages were divided into early (IA), locally advanced (IB-IIIC), and metastatic (IV) stage. Treatment use was examined according to tumor stage and location. Time trend analyses of treatment use and overall survival were conducted. RESULTS: A total of 89,098 patients with gastric adenocarcinoma were identified. In those with early-stage cancer, endoscopic treatment increased over time in patients with cardia and noncardia disease. In patients with locally advanced cardia disease, preoperative therapy use increased over time (2013-2014 [vs 2006-2008]: odds ratio [OR], 3.09; 95% confidence interval [95% CI], 2.80-3.41). In patients with locally advanced noncardia disease, the use of preoperative therapy also increased (2013-2014: OR, 3.32; 95% CI, 2.88-3.82) as did the use of perioperative therapy (2013-2014: OR, 4.21; 95% CI, 3.52-5.03) in lieu of postoperative treatment (2013-2014: OR, 0.66; 95% CI, 0.60-0.71). In patients with metastatic disease, approximately 34% of patients with cardia and 40% of patients with noncardia cancer did not receive treatment. Stage-specific and location-specific overall survival was found to improve over the study period. CONCLUSIONS: Practice patterns for the treatment of gastric cancer in the United States reflect the increased adoption of evidence-based therapies, including endoscopic resection of early-stage cancer and preoperative therapy for patients with locally advanced disease. Treatment for metastatic disease remains markedly underused. Cancer 2018;124:1122-31. © 2017 American Cancer Society.

Effect of hospital safety net designation on treatment use and survival in hepatocellular carcinoma.

BACKGROUND: Racial/ethnic minorities with hepatocellular carcinoma (HCC) have worse survival than non-Hispanic whites. Comparing patient outcomes across health care delivery systems can identify biological and care delivery mechanisms contributing to this disparity. We compared presentation, treatment, and survival of HCC patients treated at safety net hospitals (SNHs) and non-SNHs. METHODS: Patients diagnosed with HCC from 2001 to 2012 were identified in the Texas Cancer Registry. We compared hospital and patient characteristics across three hospital categories: non-SNHs, low-proportion SNHs (l-SNHs), and high-proportion SNHs (h-SNHs). Covariate-adjusted treatment use and overall survival were compared among the 3 hospital categories. RESULTS: Despite comprising only 23% of hospitals, h-SNHs cared for 42% of 17,489 HCC patients and disproportionately delivered care to racial/ethnic minorities and patients of low socioeconomic status compared with non-SNHs. Compared with non-SNHs, treatment use was similar at l-SNHs (45% vs 45%; adjusted odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06) but significantly lower at h-SNHs (32% vs 45%; OR, 0.64; 95% CI, 0.57-0.73). Similarly, patients with localized HCC were less likely to undergo curative treatment at h-SNHs than non-SNHs (OR, 0.51; 95% CI, 0.40-0.66). Compared with non-SNHs, overall survival was similar at l-SNHs (hazard ratio [HR], 0.93; 95% CI, 0.89-0.98) but significantly worse at h-SNHs (HR, 1.30; 95% CI, 1.22-1.39). CONCLUSION: Patients at SNHs are less likely to undergo HCC treatment, even when diagnosed at an early stage, which likely contributes to worse survival. System-level differences in care delivery may partly explain racial/ethnic and socioeconomic disparities in HCC prognosis. Cancer 2018;124:743-51. © 2017 American Cancer Society.

Adjuvant Therapy Is Associated With Improved Survival in Resected Perihilar Cholangiocarcinoma: A Propensity Matched Study.

BACKGROUND: There are limited well-controlled studies that conclusively demonstrate a benefit of adjuvant therapy in resected perihilar cholangiocarcinoma. Most studies include all biliary tract tumors as one entity despite the heterogeneity of these diseases. METHODS: We identified patients with resected perihilar cholangiocarcinoma from the National Cancer Database between 2006 and 2013. Patients who received adjuvant therapy (AT) were compared to an observation (OB) cohort by propensity score matching. RESULTS: We identified 1846 patients: 1053 patients (57%) in the OB group, and 793 (43%) in the AT group. Patients who received adjuvant therapy were more likely to be younger, have a higher rate of private insurance, have higher T and N stage tumors, and were more likely to have positive resection margins. After 1:1 propensity score matching, 577 OB group patients were compared with 577 AT group patients. The AT cohort was associated with better overall survival compared with the OB cohort (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.64-0.83). The median survival was 29.5 and 23.3 months for the AT and OB groups, respectively (P < 0.01). Subgroup analysis demonstrated a survival advantage for adjuvant therapy in disease with positive resection margins (HR 0.53; 95% CI 0.42-0.67). CONCLUSIONS: Adjuvant therapy is associated with improved survival in resected perihilar cholangiocarcinoma, especially in disease with positive resection margins. This study supports the use of adjuvant therapy in high-risk patients.

Comparison of Overall Survival Between Preoperative Chemotherapy and Chemoradiotherapy for Resectable Pancreatic Adenocarcinoma.

Background: Preoperative therapy is being increasingly used in the treatment of resectable pancreatic cancer. Because there are only limited data on the optimal preoperative regimen, we compared overall survival (OS) between preoperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) in resectable pancreatic adenocarcinoma. Patients and Methods: Patients receiving preoperative therapy and resection for clinical T1-3N0-1M0 adenocarcinoma of the pancreas were identified in the National Cancer Database for 2006 through 2012. We constructed inverse probability of treatment weights to balance baseline group differences, and compared OS between CT and CRT, as well as pathologic and postoperative findings. Results: We identified 1,326 patients (CT: 616; CRT: 710). Differences in OS were not significant between CRT and CT (median survival, 25 vs 26 months; P=.10; weight-adjusted hazard ratio, 0.89; 95% CI, 0.77-1.02). Compared with patients in the CT group, those in the CRT group had lower pathologic T stage (ypT0/T1/T2: 36% vs 21%; P<.01), less lymph node involvement (ypN1: 35% vs 59%; P<.01), and fewer positive resection margins (14% vs 21%; P=.01), but had more postoperative unplanned readmissions (9% vs 6%; P=.01) and increased 90-day mortality (7% vs 4%; P=.03). Those in the CRT group were also less likely to receive postoperative therapy (26% vs 51%; P<.01). Conclusions: Preoperative CT and CRT have similar OS, but CRT is associated with more favorable pathologic features at the cost of higher postoperative morbidity and mortality. Additional trials investigating preoperative therapy are needed for patients with resectable pancreatic cancer.

Racial and ethnic disparities in a national cohort of ampullary cancer patients.

BACKGROUND AND OBJECTIVES: Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. METHODS: Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. RESULTS: A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. CONCLUSIONS: Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors.

Bracketed radioactive seed localization vs bracketed wire-localization in breast surgery.

Multiple localizers placed in a bracketed fashion facilitates excision of radiographically extensive breast lesions. In this study, bracketed radioactive seed localization (bRSL) was compared to bracketed wire localization (bWL). We hypothesized that bRSL would achieve adequate margins and decrease re-operation rates with similar or less specimen volumes (SV) than bWL. Retrospective review identified patients who underwent bracketed breast procedures at an academic medical center. Data collected included patient demographics, tumor features, treatment variables, and surgical outcomes. Wilcoxon rank-sum test and chi-square test were used to compare continuous and categorical data, respectively. A multivariable logistic regression model was used to evaluate the association between re-excision and localization technique after adjusting for clinically relevant variables. Patients who underwent bWL were 3.9 times more likely to undergo re-excision compared to patients in bRSL group (OR=3.9, 95% CI: 2.0-7.4). Initial and total SV did not significantly differ between the two groups (P=.4). Patients were significantly more likely to undergo a mastectomy in the bWL group than in the bRSL group (24% vs 7%; P<.01). For patients undergoing excision of radiologically extensive breast lesions, bRSL serves as an alternative to bWL. In this retrospective study, bRSL was associated with a decreased re-excision rate with similar SV and a lower rate of mastectomy when compared to bWL.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

Vascular Invasion and Metastasis is Predictive of Outcome in Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) have variable long-term outcomes. Better delineation of prognosis is important for clinical trial enrollment and clinical practice in an era of precision medicine. We hypothesized that stratification of patients with BCLC stage C HCC by presence of vascular invasion and/or metastasis improves prognostic discrimination. Methods: Using a prospectively maintained database, we identified 234 patients diagnosed with BCLC stage C HCC between 2005 and 2015. Patients were stratified into 3 groups based on tumor characteristics: (1) vascular invasion alone, (2) metastasis alone, and (3) vascular invasion and metastasis. Overall survival (OS) was compared using a Cox model. A subgroup analysis was performed based on extent of vascular invasion and site of metastasis. Results: The cohort comprised 123 patients (53%) with vascular invasion alone, 34 (15%) with metastasis alone, and 77 (33%) with both vascular invasion and metastasis. Median survival was 5.7, 3.9, and 3.0 months, respectively (P<.01). Patients with vascular invasion or metastasis alone had significantly better survival compared with those with vascular invasion and metastasis (adjusted hazard ratio [HR],0.68; 95% CI, 0.49-0.94, and HR, 0.61; 95% CI, 0.39-0.96, respectively). Compared with tumoral invasion of branch portal veins, involvement of the main portal vein was associated with worse survival (HR, 2.13; 95% CI, 1.29-3.49). OS did not differ by site of metastasis. Conclusions: Stratification of patients within the BCLC stage C staging subgroup by vascular invasion and presence of metastasis further discriminates patient prognosis. This substratification may have implications for therapy and more accurate prognostic features.

Resident postgraduate year does not influence rate of complications following inguinal herniorrhaphy.

BACKGROUND: Previous data indicate that patients who undergo surgery with a postgraduate year 3 (PGY-3) resident as the junior surgeon have a lower rate of recurrence compared with PGY-1 and PGY-2 after an open inguinal herniorrhaphy. Lower PGY level was also associated with increased operative time. We hypothesize that when controlling for surgeon, technique, and hernia type, the outcomes for inguinal herniorrhaphy are the same independent of PGY level. MATERIALS AND METHODS: A retrospective review of all open unilateral inguinal hernia repairs done by residents who assisted the same senior surgeon at the Veterans Affairs North Texas Health Care System was performed. RESULTS: Seven hundred fifty-two open unilateral inguinal hernia were identified: mean patient age = 60.6 ± 12.7 y; mean body mass index = 27.0 ± 10.8 kg/m2; American Society of Anesthesia III-IV = 51%; and Nyhus type 2 = 44.7%, 3a = 41.6%, and 3b = 13.7%. Residents involved were PGY-1 (17.2%), PGY-2/3 (71.1%), and PGY-4/5 (11.7%). Postoperative complications for intern, junior (PGY-2 and PGY-3), and senior residents (PGY-4 and PGY-5) were 4%, 9%, and 6%, respectively (P = 0.14). Compared to interns, junior residents finished the operation 3.9 min faster (95% confidence interval = -7.5, -0.3). There was no time difference between interns and senior residents completing the operations after controlling for hernia type. Logistic regression did not identify PGY level as an independent predictor of complications or recurrence. CONCLUSIONS: There was a slight decrease in operative time when the repair was done with junior-level residents. PGY level did not influence outcomes for open, unilateral inguinal herniorrhaphy when controlled for hernia type and technique.

Predictors of a histopathologic diagnosis of complicated appendicitis.

BACKGROUND: Despite its utilization, the intraoperative (IO) assessment of complicated appendicitis (CA) is subjective. The histopathologic (HP) diagnosis should be the gold standard in identifying patients with CA; however, it is not immediately available to guide postoperative management. The objective of this study was to identify predictors of an HP diagnosis of CA. MATERIALS AND METHODS: A retrospective review of all patients who underwent appendectomy at our institution from 2011-2013 was conducted. CA was defined by perforation or abscess on pathology report. Predictors of an HP diagnosis of CA were evaluated using a multivariable regression model. RESULTS: A total of 239 of 1066 patients had CA based on IO assessment, whereas 143 of 239 patients (60%) had CA on HP and IO assessment. On multivariable analysis, an IO diagnosis of CA was associated with an HP diagnosis of CA (odds ratio [OR]: 10.92; 95% confidence interval [CI]: 7.19-16.58). Other risk factors were age (OR: 1.28; 95% CI: 1.09-1.49), number of days of pain (OR: 1.20; 95% CI: 1.07-1.37), increased heart rate (OR: 1.14; 95% CI: 1.02-1.26), appendix size (OR: 1.09; 95% CI: 1.03-1.16), and an appendicolith (OR: 1.74; 95% CI: 1.12-2.71) on preoperative CT imaging. CONCLUSIONS: In addition to age, increased heart rate, pain duration, appendix size and appendicolith, the IO assessment is also associated with an HP diagnosis of CA; however, 40% of patients were incorrectly classified. Using these predictors with improved IO grading may achieve more accurate diagnosis of CA.

Failure to rescue following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can significantly improve the survival in selected patients with peritoneal carcinomatosis. This study aims to identify perioperative patient characteristics predictive of failure to rescue (FTR), mortality following postoperative complications from CRS/HIPEC. METHODS: Patients suffering a complication following CRS/HIPEC between 2005 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program data set. FTR was defined as 30-d mortality in the setting of a complication. Patients who suffered FTR were compared against those who survived a complication (non-FTR). Predictors of FTR were identified using a multivariable logistic regression model. RESULTS: A total of 915 eligible CRS/HIPEC cases were identified. In all, 382 patients (42%) developed ≥1 postoperative complication, and 88 patients (10%) suffered ≥1 major complication. Seventeen patients died following a complication, amounting to an FTR rate of 4%. FTR patients were more likely than non-FTR patients to have dependent functional status (18% versus 2%, P = 0.01), have American Society of Anesthesiologists (ASA) class 4 status (29% versus 8%, P = 0.01), develop ≥3 complications (65% versus 24%, P < 0.01), and suffer a major complication (94% versus 20%, P < 0.01). The following were independently associated with FTR: ASA class 4 (odds ratio [OR]: 13.4, 95% confidence interval [CI], 1.2-146.8) and major complications (OR: 66.0, 95% CI, 8.4-516.6). CONCLUSIONS: ASA class 4, major morbidity, and likely dependent functional status are independent predictors of FTR following CRS/HIPEC to treat peritoneal carcinomatosis. Therefore, ASA class 4 and dependent functional status should be considered as contraindications for CRS/HIPEC and only offered in highly selective cases.

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

BACKGROUND AND OBJECTIVES: Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. METHODS: A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. RESULTS: The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls. CONCLUSIONS: Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit.

Nomogram to predict non-home discharge following pancreaticoduodenectomy in a national cohort of patients.

BACKGROUND: Despite the development of pathways to enhance recovery and discharge to home, a significant proportion of patients are discharged to inpatient facilities after pancreaticoduodenectomy (PD). The aim of this study was to determine the rate of non-home discharge (NHD) following PD in a national cohort of patients and to develop predictive nomograms for NHD. METHODS: The National Surgical Quality Improvement Program was used to construct and validate pre- and postoperative nomograms for NHD following PD. RESULTS: A total of 6856 patients who underwent PD were identified, of which 927 (13.5%) had an NHD. The independent preoperative predictors of NHD were being female, older age, higher BMI, low serum albumin, >10% weight loss, ASA class III/IV, and being diagnosed with a bile duct/ampullary neoplasm or neuroendocrine tumor. A preoperative nomogram was constructed with a concordance index of 0.77. When postoperative variables were added to the model, the concordance index increased to 0.82. The postoperative predictors of NHD were return to the operating room, length of stay of ≥14 days, and any inpatient complications. CONCLUSIONS: These nomograms could be useful risk assessment tools to predict NHD after PD and therefore facilitate patient counseling and improve resource utilization and discharge planning.

Hospital Volume and Survival After Hepatocellular Carcinoma Diagnosis.

OBJECTIVES: The association between hospital volume and outcome following high-risk low volume cancer surgery is well documented. However, this association is not well understood in cancer patients undergoing non-surgical therapies. We explored this association in a cohort of newly diagnosed patients with hepatocellular carcinoma (HCC). METHODS: Data from the 2000 through 2011 in Texas Cancer Registry were used to study adults with newly diagnosed HCC (17,231 patients from 322 hospitals). Hospital volume was stratified into low and high volume using Contal's outcome-based method. A multivariable Cox regression with shared frailty was used to evaluate the association between hospital volume and overall survival. The relationship between treatment modality and hospital volume was explored using mixed effects logistic regression. RESULTS: The majority (61%) of HCC patients were seen in 21 high-volume hospitals. An annual hospital volume cutoff point of 24 patients was determined to stratify between high- and low-volume hospitals. Patients at high-volume hospitals presented more commonly with localized disease (56 vs. 50%, P<0.01) and were more likely to receive curative therapies including surgical resection, liver transplantation, or ablation (22 vs. 12%, P<0.01). High-volume hospitals were significantly associated with improved survival (HR=0.96, 95% CI=0.94-0.98). In multivariable analysis, hospital volume was associated with increased overall treatment utilization (OR=1.3, 95% CI=1.2-1.4). CONCLUSIONS: Hospital volume is associated with improved overall survival, particularly in localized HCC. Improved survival may be mediated by increased utilization of treatments in high HCC volume hospitals.

The neutrophil to albumin ratio as a predictor of pathological complete response in rectal cancer patients following neoadjuvant chemoradiation.

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), in patients with locally advanced rectal cancer, occurs in 15-27% of patients. Because blood cell counts and albumin are a direct indicator of the host environment, a response to nCRT might be predicted by these markers. This study was carried out to determine whether the neutrophil to albumin ratio (NAR) was predictive of pCR in veteran patients. Ninety-eight patients with rectal cancer who underwent standard nCRT, followed by TME were analyzed. Pre-nCRT and post-nCRT hematologic data were collected. Univariate and multivariate analyses were carried out. Kaplan-Meier curves were constructed with our primary endpoint of pCR. Male patients (99%), age 62.4±9.1 years, BMI=27.4±5.9 kg/m, rectal cancer distance from anal verge=7.1±4.5 cm (SD), interval between nCRT and TME=8 weeks, 55% patients=low anterior resection, 95% received 5-fluorouracil, and all patients received radiation, with 15% achieving a pCR. Univariate analysis showed that pre-nCRT carcinoembryonic antigen (15.8±45.1 vs. 3.5±5.3 ng/dl; P=0.002) and the pre-nCRT NAR (16.4±4.8 vs. 14.2±1.6; P=0.002) were associated with pCR. On multivariate analysis, pre-nCRT carcinoembryonic antigen (odds ratio=0.41, 95% confidence interval 0.22-0.77) and pre-nCRT NAR (odds ratio=0.76, 95% confidence interval 0.60-0.97) remained independent predictors of pCR. Overall survival between nonresponders and pCR patients at 1, 5, and 10 years was 96, 62, and 44% versus 93, 85, and 61%, P=0.13, and disease-free survival was 95, 60, and 47% versus 93, 85, and 61%, P=0.17; respectively. Our study shows that the pre-nCRT NAR is an independent predictor of pCR. These findings should be applied to other cohorts to determine its validity and reliability for use as a potential predictor of pCR.

Advances in Local and Systemic Therapies for Hepatocellular Cancer.

Global incidence and mortality of hepatocellular carcinoma (HCC) has increased over the past two decades. Although transplantation and surgical resection offer a chance for cure and long-term survival, most patients present with more advanced tumor stage when these therapies are not possible. Although rarely curative, locoregional therapy with transarterial chemoembolization or radioembolization offers a survival benefit for those with liver-isolated HCC who are not amenable to curative therapies. Patients with metastatic disease or macrovascular invasion are treated with systemic therapy; however, median survival remains below 1 year. Patients with severe liver dysfunction or poor performance status should be treated with best supportive care given poor prognosis and no survival benefit for treatment. Lack of predictive and prognostic biomarkers in intermediate and advanced HCC tumors has hampered integration of clinical and molecular data to aid tailoring treatment decisions. However, with increasingly complex treatment decisions, optimal outcomes are achieved through multidisciplinary care.

The state of health in the Arab world, 1990-2010: an analysis of the burden of diseases, injuries, and risk factors.

BACKGROUND: The Arab world has a set of historical, geopolitical, social, cultural, and economic characteristics and has been involved in several wars that have affected the burden of disease. Moreover, financial and human resources vary widely across the region. We aimed to examine the burden of diseases and injuries in the Arab world for 1990, 2005, and 2010 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010). METHODS: We divided the 22 countries of the Arab League into three categories according to their gross national income: low-income countries (LICs; Comoros, Djibouti, Mauritania, Yemen, and Somalia), middle-income countries (MICs; Algeria, Egypt, Iraq, Jordan, Lebanon, Libya, Morocco, occupied Palestinian territory, Sudan, Syria, and Tunisia), and high-income countries (HICs; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). For the whole Arab world, each income group, and each individual country, we estimated causes of death, disability-adjusted life years (DALYs), DALY-attributable risk factors, years of life lived with disability (YLDs), years of life lost due to premature mortality (YLLs), and life expectancy by age and sex for 1990, 2005, and 2010. FINDINGS: Ischaemic heart disease was the top cause of death in the Arab world in 2010 (contributing to 14·3% of deaths), replacing lower respiratory infections, which were the leading cause of death in 1990 (11·0%). Lower respiratory infections contributed to the highest proportion of DALYs overall (6·0%), and in female indivduals (6·1%), but ischaemic heart disease was the leading cause of DALYs in male individuals (6·0%). DALYs from non-communicable diseases--especially ischaemic heart disease, mental disorders such as depression and anxiety, musculoskeletal disorders including low back pain and neck pain, diabetes, and cirrhosis--increased since 1990. Major depressive disorder was ranked first as a cause of YLDs in 1990, 2005, and 2010, and lower respiratory infections remained the leading cause of YLLs in 2010 (9·2%). The burden from HIV/AIDS also increased substantially, specifically in LICs and MICs, and road injuries continued to rank highly as a cause of death and DALYs, especially in HICs. Deaths due to suboptimal breastfeeding declined from sixth place in 1990 to tenth place in 2010, and childhood underweight declined from fifth to 11th place. INTERPRETATION: Since 1990, premature death and disability caused by communicable, newborn, nutritional, and maternal disorders (with the exception of HIV/AIDS) has decreased in the Arab world--although these disorders do still persist in LICs--whereas the burden of non-communicable diseases and injuries has increased. The changes in the burden of disease will challenge already stretched human and financial resources because many Arab countries are now dealing with both non-communicable and infectious diseases. A road map for health in the Arab world is urgently needed. FUNDING: Bill & Melinda Gates Foundation.