Aslam Ejaz

Surgery for colorectal liver metastases: The evolution of determining prognosis.

Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative factors, these have been inconsistent in accurately determining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcriptase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predicting survival after surgical resection have been supported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver metastasis. We herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergoing resection with curative intent.

Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis.

BACKGROUND Reports on recurrence and outcomes of US patients with gastric cancer are scarce. The aim of this study was to determine incidence and pattern of recurrence after curative intent surgery for gastric cancer. STUDY DESIGN Using the multi-institutional US Gastric Cancer Collaborative database, we identified 817 patients undergoing curative intent resection for gastric cancer between 2000 and 2012. Patterns and rates of recurrence along with associated risk factors were identified using adjusted regression analysis. Recurrences were classified as locoregional, peritoneal, or hematogenous. RESULTS Median patient age was 65.8 years (interquartile range [IQR] 56.4, 74.7); the majority of patients were male (n = 462, 56.6%) and white (n = 511, 62.5%). At the time of surgery, the majority of patients underwent a partial gastrectomy (n = 481, 59.2%) with a complete R0 resection achieved in 91.6% (n = 748) of patients. At the time of last follow-up, 244 (29.9%) of 817 patients developed a recurrence; 163 (66.8%) patients had recurrence at only a single site; the remaining 81 (33.2%) had multiple sites of initial recurrence. Among patients who recurred at a single site, recurrence was most common at a distant location and included hematogenous (n = 57, 23.4%) or peritoneal (n = 47, 19.3%) only metastasis. Tumors at the gastroesophageal junction (odds ratio [OR] 3.18, 95% CI 1.08 to 9.40; p = 0.04) were associated with higher risk of locoregional recurrence, while the presence of multiple lesions (OR 10.82, 95% CI 3.56 to 32.85; p < 0.001) remained associated with an increased risk of distant hematogenous recurrence after adjusted analysis. Recurrence was associated with worse survival, with a median recurrence-free survival of 10.8 months (IQR 8.9, 12.8) among those who experienced a recurrence. CONCLUSIONS Nearly one-third of patients experienced recurrence after gastric cancer surgery. The most common site of recurrence was distant.

Failure to rescue as a source of variation in hospital mortality after hepatic surgery

The mechanisms that underlie the association between high surgical volume and improved outcomes remain uncertain. This study examined the impact of complications and failure to rescue patients from these complications on mortality following hepatic resection.

Variation in triggers and use of perioperative blood transfusion in major gastrointestinal surgery

The decision to perform intraoperative blood transfusion is subject to a variety of clinical and laboratory factors. This study examined variation in haemoglobin (Hb) triggers and overall utilization of intraoperative blood transfusion, as well the impact of transfusion on perioperative outcomes.

Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis

IMPORTANCE Currently, one of the most commonly available biomarkers in the treatment of patients with colorectal liver metastases (CRLM) is the Kirsten rat sarcoma viral oncogene homolog (KRAS); however, the prognostic implications of specific mutations of the KRAS gene are still not well defined. OBJECTIVE To investigate the prognostic impact of specific KRAS mutations on patients undergoing liver resection for CRLM. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-center study was conducted from January 1, 2003, to December 31, 2013. Data about specific KRAS mutations for 331 patients who underwent hepatic resection for CRLM at Johns Hopkins Hospital between 2003 and 2013 were analyzed. Clinicopathological characteristics, perioperative details, and outcomes were stratified by specific KRAS mutation at codons 12 and 13. INTERVENTION Resection of CRLM. MAIN OUTCOMES AND MEASURES Overall survival (OS) and recurrence-free survival. RESULTS A mutated KRAS (mtKRAS) was identified in 91 patients (27.5%). At a median follow-up of 27.4 months, recurrence was observed in 48 patients (52.7%) with mtKRAS and 130 patients (54.2%) with wild-type KRAS (wtKRAS) (P = .82). Median and 5-year survival among patients with mtKRAS was 32.4 months and 32.7%, respectively, vs 58.5 months and 46.9%, respectively, for patients with wtKRAS (P = .02). Patients with KRAS codon 12 mutations had worse OS (hazard ratio [HR], 1.54; 95% CI, 1.05-2.27; P = .03) vs those with wtKRAS, whereas a KRAS codon 13 mutation was not associated with prognosis (HR, 1.47; 95% CI, 0.83-2.62; P = .19). Among the 6 most common mutations in codons 12 and 13, only G12V (HR, 1.78; 95% CI, 1.00-3.17; P = .05) and G12S (HR, 3.33; 95% CI, 1.22-9.10; P = .02) were associated with worse OS compared with patients with wtKRAS (both P < .05). Among patients who recurred, G12V (HR, 2.96; 95% CI, 1.32-6.61; P = .01), G12C (HR, 6.74; 95% CI, 2.05-22.2; P = .002), and G12S mutations (HR, 4.91; 95% CI, 1.52-15.8; P = .01) were associated with worse OS (both P < .05). CONCLUSIONS AND RELEVANCE G12V and G12S mutations of codon 12 were independent prognostic factors of worse OS. Among patients who recurred after resection of CRLM, G12V, G12C, and G12S mutations were associated with worse OS. Information on specific KRAS mutations may help individualize therapeutic and surveillance strategies for patients with resected CRLM.

Conditional Probability of Long-term Survival After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 535 Patients

IMPORTANCE Whereas conventional actuarial overall survival (OS) estimates rely exclusively on static factors determined around the time of surgery, conditional survival (CS) estimates take into account the years that a patient has already survived. OBJECTIVE To define the CS of patients following liver resection for intrahepatic cholangiocarcinoma (ICC). DESIGN, SETTING, AND PARTICIPANTS Between January 1, 1990, and December 31, 2013, a total of 535 patients who underwent resection of ICC were identified from an international multi-institutional database. In this retrospective international study conducted from January to June 2014, clinicopathological characteristics, operative details, and long-term survival data were analyzed. Conditional survival estimates were calculated as the probability of survival for an additional 3 years. INTERVENTION Resection of ICC. MAIN OUTCOMES AND MEASURES Overall survival and CS. RESULTS While actuarial OS decreased over time from 39% at 3 years to 16% at 8 years (P = .002), the 3-year CS (CS₃) increased over time among those patients who survived. The CS₃ at 5 years-the probability of surviving to postoperative year 8 after having already survived to postoperative year 5-was 65% compared with 8-year OS of 16% (P = .002). Factors that were associated with worse OS included larger tumor size (hazard ratio [HR], 1.02; 95% CI, 1.00-1.05; P = .05), multifocal disease (HR, 1.49; 95% CI, 1.19-1.86; P = .01), lymph node metastasis (HR, 2.21; 95% CI, 1.67-2.93; P < .01), and vascular invasion (HR, 1.39; 95% CI, 1.10-1.75; P = .006). The calculated CS₃ exceeded the actuarial survival for all high-risk subgroups. For example, patients with lymph node metastasis had an actuarial OS of 11% at 6 years vs a CS₃ of 49% at 3 years (Δ38%). Similarly, patients with vascular invasion had an actuarial OS of 15% at 6 years compared with a CS₃ of 50% at 3 years (Δ35%). CONCLUSIONS AND RELEVANCE Conditional survival estimates may provide critical quantitative information about the changing probability of survival over time among patients undergoing liver resection for ICC. Therefore, such estimates can be of significant value to patients and health care professionals.

Temporal Trends in Population-Based Death Rates Associated With Chronic Liver Disease and Liver Cancer in the United States Over the Last 30 Years

The health and economic burden from liver disease in the United States is substantial and rising. The objective of this study was to characterize temporal trends in mortality from chronic liver disease and liver cancer and the incidence of associated risk factors using population‐based data over the past 30 years.

Enhanced Recovery After Surgery Protocols for Open Hepatectomy—Physiology, Immunomodulation, and Implementation

There has been recent interest in enhanced-recovery after surgery (ERAS®) or “fast-track” perioperative protocols in the surgical community. The subspecialty field of colorectal surgery has been the leading adopter of ERAS protocols, with less data available regarding its adoption in hepato-pancreato-biliary surgery. This review focuses on available data pertaining to the application of ERAS to open hepatectomy. We focus on four fundamental variables that impact normal physiology and exacerbate perioperative inflammation: (1) the stress of laparotomy, (2) the use of opioids, (3) blood loss and blood product transfusions, and (4) perioperative fasting. The attenuation of these inflammatory stressors is largely responsible for the improvements in perioperative outcomes due to the implementation of ERAS-based pathways. Collectively, the data suggest that the implementation of ERAS principles should be strongly considered in all patients undergoing hepatectomy.

Prognostic Performance of Different Lymph Node Staging Systems After Curative Intent Resection for Gastric Adenocarcinoma

Objective: To compare the prognostic performance of American Joint Committee on Cancer/International Union Against Cancer seventh N stage relative to lymph node ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric adenocarcinoma. Background: Metastatic disease to the regional LN basin is a strong predictor of worse long-term outcome following curative intent resection of gastric adenocarcinoma. Methods: A total of 804 patients who underwent surgical resection of gastric adenocarcinoma were identified from a multi-institutional database. The relative discriminative abilities of the different LN staging/scoring systems were assessed using the Akaikes Information Criterion (AIC) and the Harrells concordance index (c statistic). Results: Of the 804 patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph node metastasis. Patients with ≥N1 disease had an increased risk of death (hazards ratio = 2.09, 95% confidence interval: 1.68–2.61; P < 0.001]. When assessed using categorical cutoff values, LNR had a somewhat better prognostic performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC: 4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0) outperformed other staging/scoring systems including the N score (C index: 0.632; AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR scores of 0 or 1, there was a residual heterogeneity of outcomes that was better stratified and characterized by the LODDS. Conclusions: When assessed as a categorical variable, LNR was the most powerful manner to stratify patients on the basis of LN status. LODDS was a better predicator of survival when LN status was modeled as a continuous variable, especially among those patients with either very low or high LNR.

Interhospital Transfer and Adverse Outcomes after General Surgery: Implications for Pay for Performance

BACKGROUND Interhospital transfer is frequent, and transferred patients can have worse outcomes than direct admissions. We sought to define the incidence of interhospital transfer in general surgery and evaluate its association with surgical outcomes. STUDY DESIGN The 2011 American College of Surgeons NSQIP database was used. Transferred patients were compared with urgent, inpatient direct admissions in a series of increasingly complex risk-adjustment models, including multiple regression using modified Poisson and negative binomial models, as well as propensity scores. Primary outcomes were overall complications, mortality, length of stay, and readmission. RESULTS Overall, 7% of inpatient general surgery cases were transferred in. Among urgent cases, there were 6,197 transferred patients and 47,267 direct admissions. The most common procedures for direct admissions were appendectomy and cholecystectomy, and transfers had a more complex and broader range of procedures. On unadjusted analysis, transferred patients had a much higher risk for complications (risk ratio [RR] = 1.48; 95% CI, 1.45-1.52) and mortality (RR = 2.70; 95% CI, 2.48-2.94), as well as a longer length of stay (1.74 times longer; 95% CI, 1.69-1.78) and higher risk of readmission (RR = 1.31; 95% CI, 1.20-1.44). In the most sophisticated model, the propensity score match, the difference in outcomes for transferred patients was only modestly higher or equivalent (complications: RR = 1.03; 95% CI, 1.00-1.07; mortality: RR = 0.98; 95% CI, 0.88-1.09; length of stay: 1.08 times longer; 95% CI, 1.04-1.11; readmission: RR = 0.97; 95% CI, 0.88-1.08). CONCLUSIONS Interhospital transfer is frequent in surgery. Worse outcomes seen in transferred patients are largely due to confounding by patient characteristics rather than any true harm from transfer. Pay-for-performance schemes should adjust for transfer status to avoid unfairly penalizing hospitals that frequently accept transfers.