Andrew S. Barbas

Simultaneous resections of colorectal cancer and synchronous liver metastases: A multi-institutional analysis

BackgroundThe safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections.MethodsClinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985–2006 were reviewed.Results610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (≥ three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008].ConclusionsSimultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.

The impact of portal vein resection on outcomes for hilar cholangiocarcinoma: a multi-institutional analysis of 305 cases.

BACKGROUND. Surgical strategy for hilar cholangiocarcinoma often includes hepatectomy, but the role of portal vein resection (PVR) remains controversial. In this study, the authors sought to identify factors associated with outcome after surgical management of hilar cholangiocarcinoma and examined the impact of PVR on survival.

Major Liver Resection in Elderly Patients: A Multi-Institutional Analysis

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.

Aptamer applications for targeted cancer therapy.

Aptamers are single-stranded DNA or RNA oligonucleotides that assume specific 3D structures and bind to target molecules with high affinity. The unique specificity of aptamers has made them attractive agents for targeted cancer therapy. Aptamers have been developed against a variety of cancer targets, including extracellular ligands and cell surface proteins. In addition, aptamers have been incorporated into novel constructs involving siRNAs, chemotherapeutic agents, cell toxins and nanoparticles, in which they function as delivery agents for therapeutic cargo. In this article, we review recent developments in the use of aptamers for targeted cancer therapy, particularly focusing on novel applications of aptamers targeting the cell surface.

Synchronous Colorectal Liver Metastases: Is It Time to Reconsider Traditional Paradigms of Management?

BackgroundPatients with synchronous colorectal liver metastases (CLM) are typically treated with initial colorectal resection followed by arbitrary and prolonged courses of chemotherapy. Partial hepatectomy is considered only for patients without interval disease progression. This review describes the rationale for this treatment approach and the recent developments suggesting that this management paradigm should be reconsidered.ResultsBecause asymptomatic colorectal cancer often does not lead to complications, and given the potential benefit of chemotherapy in downsizing unresectable to resectable liver disease, most patients with asymptomatic primary tumors and unresectable synchronous CLM should be first treated with chemotherapy. In contrast, initial hepatic resection should be considered for resectable synchronous CLM. Survival benefits from prehepatectomy chemotherapy have not been established. Several reports demonstrate morbidity after hepatic resection from extended durations of irinotecan- and/or oxaliplatin-based prehepatectomy chemotherapy. Although shorter treatment periods may not have these deleterious effects on subsequent hepatic resection, prospective studies reveal that most patients with supposedly aggressive disease with short treatment durations will not be identified. Moreover, a complete radiologic response to prehepatectomy chemotherapy is not only rare but also does not equate with a complete pathological response. Finally, several studies suggest that simultaneous colorectal and minor hepatic resections can performed safely with benefits in total morbidity when compared with traditional staged procedures.Conclusions The traditional treatment paradigm centering on the utility of prehepatectomy chemotherapy for resectable synchronous CLM should be reconsidered. Recent developments underscore the need for prospective randomized controlled trials evaluating the optimal timing of hepatectomy relative to chemotherapy.

Biofilms in the normal human large bowel: fact rather than fiction

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Examining Reoperation and Readmission after Hepatic Surgery

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.

Laparoscopic Versus Open Hartmann Procedure for the Emergency Treatment of Diverticulitis: A Propensity-matched Analysis

BACKGROUND: A laparoscopic approach has been proposed to reduce the high morbidity and mortality associated with the Hartmann procedure for the emergency treatment of diverticulitis. OBJECTIVE: The objective of our study was to determine whether a laparoscopic Hartmann procedure reduces early morbidity or mortality for patients undergoing an emergency operation for diverticulitis. DESIGN: This is a comparative effectiveness study. A subset of the entire American College of Surgeons National Surgical Quality Improvement Program patient sample matched on propensity for undergoing their procedure with the laparoscopic approach were used to compare postoperative outcomes between laparoscopic and open groups. SETTING: This study uses data from the American College of Surgeons National Surgical Quality Improvement Program Participant User Files from 2005 through 2009. PATIENTS: All patients who underwent an emergency laparoscopic or open partial colectomy with end colostomy for colonic diverticulitis were reviewed. MAIN OUTCOME MEASURES: The main outcome measures were 30-day mortality and morbidity. RESULTS: Included in the analysis were 1186 patients undergoing emergency partial colectomy with end colostomy for diverticulitis. Among the entire cohort, the laparoscopic group had fewer overall complications (26% vs 41.7%, p = 0.008) and shorter mean length of hospitalization (8.9 vs 11.6 days, p = 0.0008). Operative times were not significantly different between groups. When controlling for potential confounders, a laparoscopic approach was not associated with a decrease in morbidity or mortality. In comparison with a propensity-match cohort, the laparoscopic approach did not reduce postoperative morbidity or mortality. LIMITATIONS: This study is limited by its retrospective nature and the absence of pertinent variables such as postoperative pain indices, time for return of bowel function, and rates of readmission. CONCLUSIONS: A laparoscopic approach to the Hartmann procedure for the emergency treatment of complicated diverticulitis does not significantly decrease postoperative morbidity or mortality in comparison with the open technique.

Hepatic Resection for Metastatic Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era

Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer‐related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5‐year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long‐term follow‐up (10‐years) using an intention‐to‐treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow‐up from listing was 59.7 (26.8‐103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10‐year actuarial survival from transplant between groups. On an intention‐to‐treat basis, the dropout rate was higher in the M+ group and the 5‐year and 10‐year survival rates from listing were decreased in the M+ group. An alpha‐fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. Conclusion: Tumor differentiation and cancer‐related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha‐fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077‐2088)