Amy Evenson

Current Management of Enterocutaneous Fistula

Enterocutaneous fistulas, defined as abnormal communications between bowel and skin, are among the most challenging conditions managed by the general surgeon. In an era when the mortality from pan-creaticoduodenectomy is less than 3%, the mortality of enterocutaneous fistulas remains 10 to 30% due to the often-present complications of sepsis, malnutrition, and electrolyte abnormalities. Taking ad-vantage of recent advances in techniques of pre- and post-surgical management and support, employing a multidisciplinary team approach, and executing a well-delineated management plan provide the patient and surgeon with the best possibility of success in treating this potentially devastating condition.

Expression and activity of C/EBPβ and δ are upregulated by dexamethasone in skeletal muscle

The influence of glucocorticoids on the expression and activity of the transcription factors CCAAT/enhancer binding protein (C/EBP)β and δ in skeletal muscle was examined by treating rats or cultured L6 myotubes with dexamethasone. Treatment of rats with 10 mg/kg of dexamethasone resulted in increased C/EBPβ and δ DNA binding activity in the extensor digitorum longus muscle as determined by electrophoretic mobility shift assay (EMSA) and supershift analysis. A similar response was noticed in dexamethasone‐treated myotubes. In other experiments, myocytes were transfected with a plasmid containing a promoter construct consisting of multiple C/EBP binding elements upstream of a luciferase reporter gene. Treatment of these cells with dexamethasone resulted in a fourfold increase in luciferase activity, suggesting that glucocorticoids increase C/EBP‐dependent gene activation in muscle cells. In addition, dexamethasone upregulated the protein and gene expression of C/EBPβ and δ in the myotubes in a time‐ and dose‐dependent fashion as determined by Western blotting and real‐time PCR, respectively. The results suggest that glucocorticoids increase C/EBPβ and δ activity and expression through a direct effect in skeletal muscle.

Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma

Background: Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. Methods: Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The CyberknifeTM stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. Results: 34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. Conclusions: SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma.

Evaluation of Native Kidney Recovery After Simultaneous Liver-Kidney Transplantation

Background. Debate continues about which liver transplantation candidates with impaired renal function should undergo liver transplant alone versus simultaneous liver-kidney transplantation (SLK). Identifying predictors of native kidney function recovery after SLK requires an accurate measure of the relative function of all three kidneys in patients with SLK. Methods. The distance of a transplanted kidney from the renal scan camera can be substantially different from that of native kidneys. We developed a technique to correct attenuation of counts of all three kidneys based on their depth. Results. In our series of 13 SLK recipients, attenuation correction increased the measured renal function of native kidneys by up to 40%, demonstrating the importance of this procedure for accurately measuring kidney function. Eight patients met the United Network for Organ Sharing (UNOS)-proposed criteria for receiving a SLK, but four of these still had significant native kidney function (>40% of total function) after transplant. Five patients did not meet the UNOS-proposed criteria for SLK, yet only one of these had native kidney function recovery. Conclusion. The criteria proposed by UNOS to determine that SLK is indicated, and thus that native kidney recovery is not expected, are not always accurate. Further study of factors associated with native kidney recovery after SLK is required.

[18F]fludeoxyglucose positron emission tomography and computed tomography as a prognostic tool before liver transplantation, resection, and loco‐ablative therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer‐related death worldwide. Orthotopic liver transplantation (OLT) and resection are curative treatment options for well‐selected patients with HCC, whereas loco‐ablative therapy has been shown to prolong survival. Organ and treatment allocations for these patients are currently based on the number and size of tumors, as defined by the Milan criteria, and on functional capacity, and they are incorporated into the Barcelona Clinic Liver Cancer staging system and treatment strategy. Even though these staging criteria have markedly improved the outcomes of patients with HCC, they still lack accuracy in predicting the risk of tumor recurrence because they do not incorporate markers of tumor biology and behavior. Positron emission tomography (PET) and computed tomography (CT) with [18F]fludeoxyglucose ([18F]FDG) constitute an imaging modality for detecting tumor tissue that is metabolically active. Uptake of [18F]FDG is highly associated with tumor aggressiveness. In this review, we present the accumulating data on the use of [18F]FDG PET‐CT as an in vivo biomarker and its predictive value in identifying patients at risk for HCC recurrence after liver transplantation, resection, or ablation. These data suggest that the introduction of [18F]FDG PET‐CT into the imaging algorithm of patients planned for liver transplantation, resection, or ablation may improve outcomes. Liver Transpl 21:572–580, 2015.

Minimising cold ischaemic time is essential in cardiac death donor-associated liver transplantation

BACKGROUND An important issue in the transplantation of livers procured from cardiac death donors (CDDs) concerns why some centres report equivalent outcomes and others report inferior outcomes in transplantations using CDD organs compared with standard criteria donor (SCD) organs. Resolving this discrepancy may increase the number of usable organs. OBJECTIVES This study aimed to test whether differences in cold ischaemic time (CIT) are critical during CDD organ transplantation and whether such differences might explain the disparate outcomes. METHODS Results of CDD liver transplants in our own centre were compared retrospectively with results in a matched cohort of SCD liver recipients. Endpoints of primary non-function (PNF) and ischaemic cholangiopathy (IC) were used because these outcomes are clearly associated with CDD organ use. RESULTS In 22 CDD organ transplants, CIT was a strong predictor of PNF or IC (P = 0.021). Minimising CIT in CDD organ transplants produced outcomes similar to those in a matched SCD organ transplant cohort at our centre and in SCD organ transplant results nationally (1- and 3-year graft and patient survival rates: 90.9% and 73.3% vs. 77.6% and 69.2% in CDD and SCD grafts, respectively. A review of the published literature demonstrated that centres with higher CITs tend to have higher rates of PNF or IC (correlation coefficient: 0.41). CONCLUSIONS These findings suggest that a targeted effort to minimise CIT might improve outcomes and allow the safer use of CDD organs.

Utilization of kidneys from donation after circulatory determination of death.

Purpose of reviewThe present review describes the recent experience with kidney transplantation using donation after circulatory determination of death (DCDD) including efforts to expand the potential pool of DCDD donors. Recent findingsThe use of DCDD kidneys represents a growing source of kidneys for transplantation in the USA, although not to the same extent as in Europe. Expansion of the potential donor pool has included the use of kidneys with extended time to donor arrest and pediatric donors. The use of machine perfusion for DCDD kidneys has failed to demonstrate significant benefit. SummaryDCDD kidneys continue to demonstrate increased rates of delayed graft function and primary nonfunction when compared with kidneys recovered after donation after brain death (DBD) likely due to increased warm ischemic time during recovery. Despite early complications, DCDD kidneys show comparable function and survival after the immediate postoperative period and have been demonstrated to provide a survival benefit to recipients over waiting for DBD kidneys. The effect of machine perfusion on DCDD kidneys may decrease delayed graft function but has no effect on long-term function. Despite concerns, the increasing number of DCDD donors does not appear to be directly responsible for decreased numbers of DBD donors.

Prenatal Diagnosis and Subsequent Treatment of an Intermediate-Risk Paraspinal Neuroblastoma : Case Report and Review of the Literature

Objectives: Neuroblastoma is the most common extracranial solid tumor of childhood, and the most common malignancy diagnosed during infancy. In comparison, neonatal neuroblastoma is relatively rare. Improvements in prenatal imaging and widespread use of fetal ultrasonography have led to an increased rate of prenatal diagnoses. Methods: Case report and literature review. Results: We report a case of an intermediate-risk neuroblastoma, diagnosed at 36 weeks’ gestation by ultrasound and subsequently visualized by fetal MRI, that resulted in spinal cord compression and decreased fetal movement. A multidisciplinary team approach resulted in rapid delivery, evaluation, biopsy, staging, and treatment implementation in a successful effort to preserve lower extremity function. Conclusion: Prenatal diagnosis of neuroblastoma, management and outcomes are reviewed. Prompt diagnosis can strongly influence perinatal management and improve prognosis.

Concerns of ABO incompatible and crossmatch-positive potential donors and recipients about participating in kidney exchanges.

Kidney paired exchanges (KPEs) have increased, yet are still underutilized. This study aimed to develop tools for assessing KPE concerns, identify predictors of KPE concerns, and describe common KPE concerns among potential living donors (LDs) and intended recipients. Incompatible former potential LDs (n = 135) and intended recipients (n = 83) retrospectively completed questionnaires to assess KPE concerns. Healthcare system distrust also was assessed. A minority (n = 48 or 36.5% of potential LDs; n = 25 or 30.1% of intended recipients) had pursued KPE participation. Of those who pursued KPE participation, 11 (22.9%) and 6 (24.0%) completed KPE donation or transplantation, respectively. The questionnaires for potential LDs and recipients showed good internal consistency and preliminary convergent validity. LDs and patients less willing to pursue KPE reported more KPE concerns. Common KPE concerns for both potential LDs and recipients were related to perceived Distrust/Inequity and Inconvenience/Cost. Multivariate predictors of more KPE concerns were as follows: male gender (t = 4.5, p < 0.001) and more healthcare system distrust (t = 2.5, p = 0.01) for potential LDs; black race (t = 2.1, p = 0.04) and more healthcare system distrust (t = 2.3, p = 0.03) for intended recipients. These findings underscore the importance of addressing concerns potential LDs and patients have about KPE if the true potential of KPE is to be realized.

Emergency hernia repair in cirrhotic patients with ascites.

BACKGROUND The optimal treatment for abdominal wall hernias in the setting of ascites is not clear. We describe our experience with emergent surgery for hernias in patients with cirrhosis and ascites and assess variables associated with poor short- and long-term outcomes to inform decisions about aggressive early repair. METHODS We performed a retrospective review of all emergency abdominal wall hernia repairs admitted from the emergency department from January 2000 to December 2011 in all patients with ascites caused by liver cirrhosis. Demographic data, comorbidities, complications, operative details, hospital length of stay, and admission model of end-stage liver disease (MELD) score was determined. Follow-up was detailed via comprehensive liver service electronic records. RESULTS There were 69 emergent hernia surgeries in 68 patients during the study period. There were two early deaths (both MELD score> 20). Multivariate analysis revealed MELD score (18% increase in risk with each point of MELD), preoperative anemia (sevenfold increase in risk), and preoperative small bowel obstruction (ninefold increase in risk) as predictive factors of major complication. In patients with MELD score greater than 10, morbidity was more than 50%, and major morbidity is greater than 12% when MELD score is greater than 20. CONCLUSION Emergent hernia surgery in patients with ascites has low mortality but high morbidity and requires intense use of resources. To decrease the incidence of emergent hernia surgery, we recommend the aggressive use of elective repair. Emergent hernia repair, when necessary, should be performed at experienced centers and must include adequate ascites control with diuretic therapy and percutaneous paracentesis. Preoperative anemia and electrolyte abnormalities should be aggressively treated. Finally, while wound complications are common and frequently require reintervention, they are not associated with increased mortality. LEVEL OF EVIDENCE Prognostic and epidemiologic study, level V.