Troponin Elevation After Colorectal Surgery: Significance and Management.

OBJECTIVE: The aim of this study is to identify the association between early postoperative troponin elevations and outcomes after major colorectal surgery. BACKGROUND: Myocardial infarction is the leading cause of death after noncardiac surgery. Most postoperative myocardial infarctions are clinically silent, and asymptomatic troponin elevations have the same early mortality as symptomatic infarctions. METHODS: Patients over the age of 45, undergoing major colorectal surgery from March 2015 to January 2016, were identified. Plasma troponin T concentrations were prospectively collected within 24 and 48 hours after surgery. Characteristics, evaluations, management, and outcomes of patients with elevated troponin concentrations were analyzed. Mortality within the follow-up period was the primary end point. RESULTS: A total of 1020 patients were screened with postoperative troponin concentrations. Fifty patients had troponin concentrations >0.01 ng/mL. Patients rarely (16%) had ischemic symptoms. Cardiology was consulted for 23 patients and started on medical therapy. Seventeen of these patients were alive at follow-up. Ten patients (20%) with troponin concentrations >0.01 ng/mL died within the follow-up period, 7 of which had concentrations ≥0.03 ng/mL. CONCLUSIONS: Most postoperative myocardial injury is asymptomatic and may only be detected by routine troponin screening. Elevated troponin concentrations after colorectal surgery may facilitate identifying patients at postoperative risk and prompt appropriate testing. Early intervention in select patients may lead to potential reduction of mortality after major colorectal surgery.

Factors affecting the surgical approach and timing of bilateral adrenalectomy.

BACKGROUND: Laparoscopic adrenalectomy has gained widespread acceptance. However, the optimal surgical approach to laparoscopic bilateral adrenalectomy has not been clearly defined. The aim of this study is to analyze the patient and intraoperative factors affecting the feasibility and outcome of different surgical approaches to define an algorithm for bilateral adrenalectomy. METHODS: Between 2000 and 2013, all patients who underwent bilateral adrenalectomy at a single institution were selected for retrospective analysis. Patient factors, surgical approach, operative outcomes, and complications were analyzed. RESULTS: From 2000 to 2013, 28 patients underwent bilateral adrenalectomy. Patient diagnoses included Cushing's disease (n = 19), pheochromocytoma (n = 7), and adrenal metastasis (n = 2). Of these 28 patients, successful laparoscopic adrenalectomy was performed in all but 2 patients. Twenty-three out of the 26 adrenalectomies were completed in a single stage, while three were performed as a staged approach due to deterioration in intraoperative respiratory status in two patients and patient body habitus in one. Of the adrenalectomies completed using the minimally invasive approach, a posterior retroperitoneal (PR) approach was performed in 17 patients and lateral transabdominal (LT) approach in 9 patients. Patients who underwent a LT approach had higher BMI, larger tumor size, and other concomitant intraabdominal pathology. Hospital stay for laparoscopic adrenalectomy was 3.5 days compared to 5 and 12 days for the two open cases. There were no 30-day hospital mortality and 5 patients had minor complications for the entire cohort. CONCLUSIONS: A minimally invasive operation is feasible in 93% of patients undergoing bilateral adrenalectomy with 65% of adrenalectomies performed using the PR approach. Indications for the LT approach include morbid obesity, tumor size >6 cm, and other concomitant intraabdominal pathology. Single-stage adrenalectomies are feasible in most patients, with prolonged operative time causing respiratory instability being the main indication for a staged approach.

KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies.

Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.

Combined Primary Resection with Hepatic Artery Infusion Pump Implantation Is Safe for Unresectable Colorectal Liver Metastases.

BACKGROUND: Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established. METHODS: Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics. RESULTS: Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS). CONCLUSION: Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing.

Single-Center Experience with Magnetic Retraction in Colorectal Surgery.

Background: Appropriate tissue retraction is essential in laparoscopic surgery, and colorectal operations often require an additional incision and trocar that can disturb visualization and maneuverability. Each incision carries an increased risk for complications as well as increased pain and cosmetic issues. Magnetic devices have been developed for a less invasive retraction. The objective of this study is to report our initial experience using magnet retraction. Methods: Ten consecutive patients who underwent laparoscopic colorectal procedures by a single surgeon using a magnetic retractor (Levita Magnetics® Surgical System, San Mateo, CA) between October 2017 and June 2018 at Duke Regional Hospital in Durham, NC, were included. Results: The cases included four single-port right colectomies, one sigmoidectomy, and five rectopexies. Nine cases were completed laparoscopically, as one right colectomy required conversion due to adhesions and bulky specimen. Indications included adenocarcinoma, diverticular disease, and rectal prolapse. The magnet was successfully used for uterus, colon, or colonic pedicle retraction. No intraoperative or 30-day complications were observed. Conclusion: Magnetic surgical retractors are a safe, dynamic, and incision-less option for surgical field exposure during laparoscopic colorectal surgery. Reduced trocars decrease tissue trauma, enhances maneuverability, and potentially improves outcomes; however, further studies are required.

Long-term histological effects of preemptive antiviral therapy in liver transplant recipients with hepatitis C virus infection.

The long-term effects of preemptive antiviral therapy on fibrosis progression in liver transplant recipients with hepatitis C virus (HCV) were examined in a cohort of consecutive liver transplant recipients who received preemptive antiviral therapy for 48 weeks (95% were virologic nonresponders). Control patients were transplanted during this same period but did not receive preemptive therapy. Patients were followed to the date of last biopsy and censored at the time of subsequent HCV treatment. Eighty-six patients surviving >/=90 days were included. Treated and control patients were similar, except that treated patients had longer histological follow-up (60 versus 50 months), a lower median Model for End-Stage Liver Disease score at liver transplant (17 versus 23), and a shorter median length of hospital stay (6 versus 9.5 days). In the uncensored analysis, the cumulative probability of a Batts-Ludwig fibrosis score >/= 2 at 48 months post-liver transplant was 22% in the preemptive therapy group and 49% in the nonpreemptive therapy group (P = 0.08). In multivariate analysis, preemptive therapy was associated with a 48% reduced risk of a fibrosis score >/= 2 (hazard ratio = 0.52, 95% confidence interval = 0.24-1.12, P = 0.09), but this failed to achieve statistical significance. Receipt of preemptive therapy was associated with a delay in subsequent HCV therapy for moderate to severe disease (fibrosis score >/= 2 or moderate necroinflammatory activity) with a median time of 36.3 months versus 20.3 months in the preemptive and nonpreemptive groups (P = 0.004). We conclude that preemptive antiviral therapy in virologic nonresponders delays the time to subsequent HCV treatment and may confer a reduced risk of fibrosis progression. Further study of preemptive antiviral therapy is warranted.

Positron emission tomography in hepatobiliary and pancreatic malignancies: a review.

BACKGROUND: The prognosis for hepatobiliary and pancreatic malignancies is dismal. Surgery remains the primary curative option, but unresectable disease is often discovered during operative exploration. Positron emission tomography (PET) provides unique biological information different from current imaging modalities. The role of PET in detecting hepatobiliary and pancreatic malignancies has not yet been established. The purpose of this article was to review the literature on the use of PET in hepatobiliary and pancreatic malignancies. DATA SOURCES: We performed an extensive search on PubMed using PET and hepatocellular, pancreatic, gallbladder, and cholangiocarcinoma as keywords, excluding articles not written in English or on nonhuman subjects, case reports, and series with <5 patients. CONCLUSIONS: Although PET has shown usefulness in the diagnosis of certain cancers, current literature cautions against the use of PET for determining malignant potential of primary liver and pancreatic lesions. Literature on PET more strongly supports clinical roles for restaging of hepatobiliary and pancreatic malignancies, and for identifying metastatic disease.

Liver-specific loss of beta-catenin results in delayed hepatocyte proliferation after partial hepatectomy.

UNLABELLED: Recent studies have suggested that beta-catenin is involved in the regulation of hepatocyte proliferation in multiple contexts, including organ development and tumorigenesis. We explored the role of beta-catenin during liver regeneration using T cell factor/lymphoid enhancer factor (TCF/LEF)-reporter mice (TOPGal mice) and liver-specific beta-catenin knockout mice. Liver-specific beta-catenin knockout mice showed a delayed onset of DNA synthesis after hepatectomy, whereas recovery of liver mass was not affected. Among putative beta-catenin target genes examined, the induction of Ccnd1 expression was reduced, whereas the expression of Myc and Egfr was unaffected. Furthermore, cyclin D1 protein levels were not induced, and the expression of cyclins A, E, and proliferating cell nuclear antigen was delayed. Intriguingly, the analysis of TOPGal mice showed that hepatocytes with active TCF/LEF transcription are confined to the pericentral zone and are not increased in number during regeneration, indicating an uncoupling between beta-catenin/TCF signaling activity and hepatocyte proliferation. CONCLUSION: Our results indicate that beta-catenin is critical for the proper regulation of hepatocyte proliferation during liver regeneration; however, the activity of beta-catenin/TCF signaling does not correlate with hepatocyte proliferation, suggesting that this regulation might be indirect/secondary.

Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice.

There is accumulating evidence that Wnt/beta-catenin signaling is involved in the regulation of liver development and physiology. The presence of genetic alterations resulting in constitutive beta-catenin stabilization in human and murine liver tumors also implicates this pathway in hepatocyte proliferation. In the present study, we generated hepatocyte-specific beta-catenin knockout mice to explore the role of beta-catenin in liver function. Conditional knockout mice were born at the expected Mendelian ratio and developed normally to adulthood, indicating beta-catenin is dispensable for essential liver function under normal breeding conditions. However, the liver mass of knockout mice was 20% less than those of mice in the control groups. Expression analysis revealed loss of genes required for glutamine synthesis in knockout mice. Loss of the liver glutamine synthesis pathway did not affect the blood ammonia level in mice fed a standard diet, yet, knockout mice showed significantly elevated blood ammonia levels with high-protein dietary feeding. Furthermore, the expression of two cytochrome P450 enzymes, CYP1A2 and CYP2E1, was almost completely abolished in livers from hepatocyte-specific beta-catenin knockout mice. Consequently, these mice were resistant to acetaminophen challenge, confirming the requirement of these cytochrome P450 enzymes for metabolism of xenobiotic substances. In conclusion, in addition to regulating hepatocyte proliferation, beta-catenin may also control multiple aspects of normal liver function.