Zhi Ven Fong

The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review.

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver‐European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines. Cancer 2014;120:2824–2838.

Biomarkers in pancreatic cancer: diagnostic, prognostic, and predictive.

Abstract Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. There has been minimal progress with regard to cancer-specific outcomes in recent decades. Although effective therapies will undoubtedly change the natural history of the disease, effective biomarkers are a promising tool that will likely have a positive impact and will undoubtedly have an important role in the management of patients with pancreatic ductal adenocarcinoma (PDA) in the future. At present, serum CA-19-9 (carbohydrate antigen 19-9) is the only Food and Drug Administration–approved biomarker for PDA, and it has utility as a prognostic marker and as a marker of disease recurrence. There has been a recent explosion in the pancreatic cancer biomarker field with more than 2000 biomarker studies implicating thousands of informative genes as candidate biomarkers. In this review, we summarize the literature on CA-19-9 in PDA and highlight the most promising investigational biomarkers. Distinctions are made between diagnostic biomarkers (detection of disease), prognostic biomarkers (provide information on prognosis and recurrence pattern), and predictive biomarkers (predict treatment response).

Comparison of melanoma guidelines in the U.S.A., Canada, Europe, Australia and New Zealand: a critical appraisal and comprehensive review

There are several well‐established guidelines for the staging of melanoma and the size of excisional margins, along with recommendations for sentinel lymph node biopsy. Guidelines have been proposed in the U.S.A. (National Comprehensive Cancer Network), Canada (Cancer Care Ontario and Canadian Medical Association), Europe (European Society for Medical Oncology) and Australia and New Zealand (Australian Cancer Network). The guidelines set by these groups are largely based on current evidence, or expert panel consensus where evidence is lacking. The recommendations are more controversial and varying where there is a lack of level‐one evidence in the literature (e.g. screening, adjuvant therapy, follow‐up intensity). We review the evidence and available literature for the management of melanoma worldwide.

Risk-adjusted Outcomes of Clinically Relevant Pancreatic Fistula Following Pancreatoduodenectomy: A Model for Performance Evaluation.

Objective: To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator. Background: Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of interest and (2) a comprehensive risk-adjustment process to control for differences in patient risk. Methods: This multinational, retrospective study of 4301 pancreatoduodenectomies involved 55 surgeons at 15 institutions. Risk for CR-POPF was assessed using the previously validated Fistula Risk Score, and pancreatic fistulas were stratified by International Study Group criteria. CR-POPF variability was evaluated and hierarchical regression analysis assessed individual surgeon and institutional performance. Results: There was considerable variability in both CR-POPF risk and occurrence. Factors increasing the risk for CR-POPF development included increasing Fistula Risk Score (odds ratio 1.49 per point, P < 0.00001) and octreotide (odds ratio 3.30, P < 0.00001). When adjusting for risk, performance outliers were identified at the surgeon and institutional levels. Of the top 10 surgeons (≥15 cases) for nonrisk-adjusted performance, only 6 remained in this high-performing category following risk adjustment. Conclusions: This analysis of pancreatic fistulas following pancreatoduodenectomy demonstrates considerable variability in both the risk and occurrence of CR-POPF among surgeons and institutions. Disparities in patient risk between providers reinforce the need for comprehensive, risk-adjusted modeling when assessing performance based on procedure-specific complications. Furthermore, beyond inherent patient risk factors, surgical decision-making influences fistula outcomes.

Incorporation of Procedure-specific Risk Into the ACS-NSQIP Surgical Risk Calculator Improves the Prediction of Morbidity and Mortality After Pancreatoduodenectomy.

Objective: This multicenter study sought to evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Programs (ACS-NSQIP) surgical risk calculator for predicting outcomes after pancreatoduodenectomy (PD) and to determine whether incorporating other factors improves its predictive capacity. Background: The ACS-NSQIP surgical risk calculator has been proposed as a decision-support tool to predict complication risk after various operations. Although it considers 21 preoperative factors, it does not include procedure-specific variables, which have demonstrated a strong predictive capacity for the most common and morbid complication after PD – clinically relevant pancreatic fistula (CR-POPF). The validated Fistula Risk Score (FRS) intraoperatively predicts the occurrence of CR-POPF and serious complications after PD. Methods: This study of 1480 PDs involved 47 surgeons at 17 high-volume institutions. Patient complication risk was calculated using both the universal calculator and a procedure-specific model that incorporated the FRS and surgeon/institutional factors. The performance of each model was compared using the c-statistic and Brier score. Results: The FRS was significantly associated with 30-day mortality, 90-day mortality, serious complications, and reoperation (all P < 0.0001). The procedure-specific model outperformed the universal calculator for 30-day mortality (c-statistic: 0.79 vs 0.68; Brier score: 0.020 vs 0.021), 90-day mortality, serious complications, and reoperation. Neither surgeon experience nor institutional volume significantly predicted mortality; however, surgeons with a career PD volume >450 were less likely to have serious complications (P < 0.001) or perform reoperations (P < 0.001). Conclusions: Procedure-specific complication risk influences outcomes after pancreatoduodenectomy; therefore, risk adjustment for performance assessment and comparative research should consider these preoperative and intraoperative factors along with conventional ACS-NSQIP preoperative variables.

Discordance Between Perioperative Antibiotic Prophylaxis and Wound Infection Cultures in Patients Undergoing Pancreaticoduodenectomy

IMPORTANCE Wound infections after pancreaticoduodenectomy (PD) are common. The standard antibiotic prophylaxis given to prevent the infections is often a cephalosporin. However, this decision is rarely guided by microbiology data pertinent to PD, particularly in patients with biliary stents. OBJECTIVE To analyze the microbiology of post-PD wound infection cultures and the effectiveness of institution-based perioperative antibiotic protocols. DESIGN, SETTING, AND PARTICIPANTS The pancreatic resection databases of 3 institutions (designated as institutions A, B, or C) were queried on patients undergoing PD from June 1, 2008, to June 1, 2013, and a total of 1623 patients were identified. Perioperative variables as well as microbiology data for intraoperative bile and postoperative wound cultures were analyzed from June 1, 2008, to June 1, 2013. INTERVENTIONS Perioperative antibiotic administration. MAIN OUTCOMES AND MEASURES Wound infection microbiology analysis and resistance patterns. RESULTS Of the 1623 patients who underwent PD, 133 with wound infections (8.2%) were identified. The wound infection rate did not differ significantly across the 3 institutions. The predominant perioperative antibiotics used at institutions A, B, and C were cefoxitin sodium, cefazolin sodium with metronidazole, and ampicillin sodium-sulbactam sodium, respectively. Of the 133 wound infections, 89 (67.1%) were deep-tissue infection, occurring at a median of 8 (range, 1-57) days after PD. A total of 53 (40.0%) of the wound infections required home visiting nurse services on discharge, and 73 (29.1%) of all PD readmissions were attributed to wound infection. Preoperative biliary stenting was the strongest predictor of postoperative wound infection (odds ratio, 2.5; 95% CI, 1.58-3.88; P = .03). There was marked institutional variation in the type of microorganisms cultured from both the intraoperative bile and wound infection cultures (Streptococcus pneumoniae, 114 cultures [47.9%] in institution A vs 3 [4.5%] in institution B; P = .001) and wound infection cultures (predominant microorganism in institution A: Enterococcus faecalis, 18 cultures [51.4%]; institution B: Staphylococcus aureus, 8 [43.9%]; and institution C: Escherichia coli, 17 [36.2%], P = .001). Similarly, antibiotic resistance patterns varied (resistance pattern in institution A: cefoxitin, 29 cultures [53.1%]; institution B: ampicillin-sulbactam, 9 [69.2%]; and institution C: penicillin, 32 [72.7%], P < .001). Microorganisms isolated in intraoperative bile cultures were similar to those identified in wound cultures in patients with post-PD wound infections. CONCLUSIONS AND RELEVANCE The findings of this large-scale, multi-institutional study indicate that intraoperative bile cultures should be routinely obtained in patients who underwent preoperative endoscopic retrograde cholangiopancreatography since the isolated microorganisms closely correlate with those identified on postoperative wound cultures. Institution-specific internal reviews should amend current protocols for antibiotic prophylaxis to reduce the incidence of wound infections following PD.

Recurrence and Survival After Resection of Small Intraductal Papillary Mucinous Neoplasm-associated Carcinomas (≤20-mm Invasive Component): A Multi-institutional Analysis.

Background:Early invasive carcinoma may be encountered in association with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The natural history of these early invasive lesions is unknown. Methods:Pancreatic surgical databases from 4 high-volume centers were queried for IPMNs, with invasive components measuring 20 mm or less. All cases were reviewed by GI gastrointestinal pathologists, and pathologic features were analyzed to identify predictors of recurrence and survival. Results:A total of 70 small IPMN-associated invasive carcinomas (⩽20-mm invasion) were identified, comprising 25% of resected IPMN-associated carcinomas (n = 280). Most of these small invasive cancers were multifocal (66%), less than 10 mm in size (73%), and arose in the setting of a main duct IPMN (96%). The most common adenocarcinoma subtypes were tubular (57%) and colloid (29%). Lymph node metastases were present in 19% of cases and 23% were T3 lesions. The overall recurrence rate was 24% (n = 17), and the median time to recurrence was 16 months (range: 4–132 months). Median and 5-year survival rates were 99 months and 59%. Recurrence patterns of invasive disease were local in 35%, distant in 47%, and both in 18%. Lymphatic spread and T3 stage were predictive of recurrence (univariate, P = 0.006), whereas tubular carcinoma type was the most predictive of poor overall survival (multivariate hazard ratio = 3.7, P = 0.04). Conclusions:This study represents the largest multi-institutional experience of resected small IPMN-associated carcinoma. Although these malignancies may frequently be cured with resection, recurrence risk is significant. Lymphatic spread, increased T stage, and tubular type carcinoma were associated with the poorest outcome.

Preoperative biliary drainage does not increase major complications in pancreaticoduodenectomy: a large single center experience from the Massachusetts General Hospital.

The impact of preoperative biliary drainage (PBD) on perioperative morbidity and mortality in pancreatic surgery is still under debate. The aim of this study was to investigate outcomes of stented vs. non‐stented patients undergoing pancreatoduodenectomy (PD).

Sarcoid-Reaction Mimicking Metastatic Malignant Hepatopancreatobiliary Tumors: Report of Two Cases and Review of the Literature

IntroductionSarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of systemic non-caseating granulomas; however, a variation of this disease known as “sarcoid-like reaction” has been described in patients with underlying cancer.ReportSarcoid-like reactions in patients with hepatopancreatobiliary (HPB) tumors are rare findings, with only 15 cases having been reported in the English language literature. These reactions can be found in local lymph nodes or in distant organs, and when present in patients with cancer, they can mimic metastatic disease on imaging, potentially resulting in incorrect cancer staging and management.DiscussionWe describe two cases of patients with HPB tumors who had distant organ disease on cross-sectional imaging suspicious for metastases, which on further workup were found to be sarcoid-like reactions. We also discuss malignancy-induced sarcoid-like reactions and provide a review of the literature of sarcoid-like reactions in the setting of HPB tumors.

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current State of the Art and Ongoing Controversies.

With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms.