HCC Liver Transplantation Wait List Dropout Rates Before and After the Mandated 6-Month Wait Time.

BACKGROUND: Studies have shown significant improvement in hepatocellular carcinoma (HCC) recurrence rates after liver transplantation since the united network of organ sharing (UNOS) implementation of a 6-month wait period prior to accrued exception model for end-stage liver disease (MELD) points enacted on October 8, 2015. However, few have examined the impact on HCC dropout rates for patients awaiting liver transplant. Our objective is to evaluate the outcomes of HCC dropout rates before and after the mandatory 6-month wait policy enacted. METHODS: We conducted a retrospective cohort study on adult patients added to the liver transplant wait list between January 1, 2012, and March 8, 2019 (n = 767). Information was obtained through electronic medical records and organ procurement and transplant network (OPTN) publicly available national data reports. RESULTS: In response to the 2015 UNOS-mandated 6-month wait time, dropout rates in the HCC patient population at our center increased from 12% pre-mandate to 20.8% post-mandate This increase was similarly reflected in the national dropout rate, which also increased from 26.3% pre-mandate to 29.0% post-mandate. DISCUSSION: From these changes, it is evident that the UNOS mandate achieved its goal of increasing equity of liver organ allocation, but HCC patients are nonetheless dropping off of the wait list at an increased rate and are therefore disadvantaged.

Outcomes in Hepatocellular Carcinoma Liver Transplantation before and after the Mandated Six-Month Wait Time.

The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018. Patients were classified into prepolicy or postpolicy groups based on 964 days before or after the wait-time policy. We also retrieved national survival outcome data from United Network for Organ Sharing. Differences across compared groups for continuous variables were assessed using the independent sample t test, and the chi-squared test was used for binary variables. We found statistical differences in recipient age (P = 0.005), days on wait-list (P = 0.001), sustained virological response (P < 0.001), and hepatocellular carcinoma recurrence one year posttransplant (P = 0.04). There were statistically significant differences in the number of treatment days pretransplant and length of transplant admission stay, indicating an increase in resource utilization in the postpolicy group. No statistically significant differences were found between groups in one-year graft or patient survival despite an observed increase in resource utilization by the hepatocellular carcinoma postpolicy group.

Incisional Hernia Repairs after Abdominal Organ Transplantation.

Incisional hernias occur after abdominal organ transplantation with rates of 1.6 per cent to 18 per cent in kidney transplants (KTs) and 1.7 to 32.4 per cent in liver transplants (LTs). We hypothesized a difference in KT and LT outcomes in patients with and without repair of incisional hernias. We conducted a retrospective cohort study of abdominal transplants from 2012 through 2016. The difference across compared groups for continuous variables was assessed using the independent sample t test, and for binary variables, using the chi-squared test. A total of 1518 transplants were performed, including 1138 KTs and 380 LTs. There were 83 KT incisional hernias (67 repaired) and 59 LT incisional hernias (48 repaired). There was no difference between groups with regard to smoking, diabetes, age, BMI, days on dialysis (KTs), pretransplant Model for End-Stage Liver Disease (MELD) (LTs), cold ischemic time, graft survival, or recurrence rate by repair method. In the LT population, there was a statistically significant difference in days on the waitlist (P = 0.02), drain placement (P = 0.04), and cytomegalovirus (CMV) mismatch (P = 0.02). Patient survival was also statistically significant for KTs (P = 0.04) and LTs (P = 0.01). KT and LT patients who have their incisional hernias repaired have better overall survival, regardless of the repair technique.

Import kidney offers and DonorNet: a view from the trenches.

The ability of DonorNet2007(®) screening functions to expedite placement of locally rejected kidneys is unknown. We separately evaluated non-mandatory share regional (n = 641) and national (n = 720) kidney offers to our center between 5/2007 and 2/2009 for cold ischemia time at offer (oCIT) with respect to candidate ranking to identify donor factors associated with early oCIT and assess the impact of screening functions. oCIT was <7 h after recovery in 83.2% of regional and 34% of national offers. Of national offers, donor characteristics significantly (p < 0.05) associated with oCIT less than median (10 h) were as follows: age <4 yr (vs. 4-35 yr), age >69 yr (vs. 60-69 yr), serum creatinine peak >2.0 and terminal >2.0 mg/dL, and glomerulosclerosis >15% (vs. 0-5%). The trend in early offers was predominantly attributed to greater proportions of pre-recovery offers. Only one factor, age >69 yr, was significantly associated with proportionately more offers at low sequence numbers. Our data suggest an effect of age within DonorNet(®) screening functions to reduce candidate list size and result in earlier offers. Shorter offer oCITs are otherwise occur largely because of pre-recovery offers from donors with certain types of pre-recovery characteristics.

Apoptosis is differentially regulated by burn severity and dermal location.

BACKGROUND: The cellular processes that contribute to cell death in burns are poorly understood. This study evaluated the distribution and extent of apoptosis in an established rat model of acute dermal burn injury. MATERIALS AND METHODS: A branding iron (100 degrees C) was applied to the depilated dorsum of seven rats, creating burn contact times of 1-8, 10, 12, and 14 s. Biopsies were collected and immunohistochemistry performed for apoptosis and cell injury/necrosis by detection of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and high-mobility group box 1 (HMGB1), respectively. The slides were scored by evaluating staining in superficial, middle, and deep dermal fields. Within these, basal keratinocytes of the epidermis, mesenchymal cells, adnexal epithelia, and vasculature wall cells were morphometrically analyzed for stain detection of selected markers. RESULTS: TUNEL staining had an inverse relationship with contact time in most fields except in deep dermal mesenchymal cells where it was increased. HMGB1 nuclear staining was significantly decreased with progressive contact time consistent with transition to cell injury/necrosis. CONCLUSIONS: This study is the first to demonstrate that apoptosis rate is dependent on dermal location, cell type, and severity of thermal injury. Furthermore, this work suggests that for most dermal locations increased thermal injury corresponds with decreased apoptosis and increased cell injury/necrosis. Together, these findings indicate that many parameters can regulate apoptosis in burn wounds, and these results will be critical to understanding burn pathogenesis and assessing future therapies.

Pharmacologic modification to resuscitation fluid after thermal injury--is drotrecogin alfa the answer to arrest burn depth progression?

HYPOTHESIS: The addition of drotrecogin alfa (DA), an anti-inflammatory useful in septic shock, to standard burn shock resuscitation fluids will protect burned, injured skin from further injury. METHODS: Anesthetized animals were subjected to a standardized burn pattern by applying a branding iron to 10 different locations on the back of the rat for 1 seconds to 14 seconds, creating a range of burn depths and severities. DESIGN: Animal burn shock and resuscitation model. PARTICIPANTS: Thirty-one male adult Sprague-Dawley rats. INTERVENTIONS: Control animals were resuscitated with lactated Ringer's solution (LRS) at 2 mL/kg/percent total body surface area/24 h; experimental animals received LRS plus DA 24 microg/kg/h (LRS + DA). OUTCOME MEASURES: Perfusion to each burned area was assessed using a laser Doppler imaging technology. Punch biopsies at each burned area were stained with hematoxylin and eosin and assessed for burn depth and for inflammation using previously reported measures. Samples from 14 animals were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and caspase-3 (apoptosis markers). RESULTS: Increasing branding iron contact times worsened perfusion, burn depth, and apoptotic ratios. There was no correlation between inflammatory markers and burn contact time. The addition of DA leads to worse perfusion, deeper burns, worse inflammation, and decreased apoptotic ratios. CONCLUSIONS: Laser Doppler imaging is a useful technology to assess burn depth. The addition of DA to traditional resuscitation fluids for burn shock is deleterious to the injured, burned skin. Modifying the traditional burn shock resuscitation fluids, although intellectually attractive, needs to be rigorously studied.

Expanding the indications for laparoscopic gastric resection for gastrointestinal stromal tumors.

OBJECTIVE: Laparoscopic resection of large gastric gastrointestinal stromal tumors (GIST) has been controversial. This generally has been limited to small lesions. We hypothesize that laparoscopic mobilization and resection using, in some cases, extracorporeal anastomosis of the gastrointestinal (GI) tract is an oncologically safe alternative to open surgery even when tumors are large. METHODS: Four patients underwent a laparoscopic approach for gastric GIST tumors >2 cm at Methodist Dallas Medical Center over a 6-month period. Patient demographics, operative findings, postoperative course, and pathologic characteristics were examined. RESULTS: The mean age in this patient group was 58 years (range, 36 to 77). Gastrointestinal bleeding and dyspepsia were the most common symptoms. Seventy-five percent of the patients were females. Mean tumor size was 10 cm (range, 2.5 to 20) with distribution in the stomach as follows: 75% greater curvature and 25% antrum. Tumors were removed by wedge, sleeve, and partial gastrectomies. Two of these tumors showed a high grade and the other 2 a moderate grade of differentiation. The number of mitoses was <5/50 HPF in all the tumors. No intraoperative spillage occurred in any patients, even with the largest tumor (20 cm). Importantly, all tumors were excised with a negative gross and microscopic margin. Average length of stay was 4 days. No patients required reoperation, and there were no complications postoperatively. CONCLUSION: Minimally invasive assisted approaches may be an option to treat large GIST tumors. Obeying principles of minimal touch, no spillage, and obtaining a negative margin, a safe operation with a laparoscopic approach is feasible, even in giant tumors. The large size of diagnosed GIST tumors should not preclude a minimally invasive approach.

Morphological parameters for assessment of burn severity in an acute burn injury rat model.

Determination of burn severity (i.e. burn depth) is important for effective medical management and treatment. Using a recently described acute burn model, we studied various morphological parameters to detect burn severity. Anaesthetized Sprague-Dawley rats received burns of various severity (0- to 14-s contact time) followed by standard resuscitation using intravenous fluids. Biopsies were taken from each site after 5 h, tissues fixed in 10% neutral-buffered formalin, processed and stained with haematoxylin and eosin. Superficial burn changes in the epidermis included early keratinocyte swelling progressing to epidermal thinning and nuclear elongation in deeper burns. Subepidermal vesicle formation generally decreased with deeper burns and typically contained grey foamy fluid. Dermal burns were typified by hyalinized collagen and a lack of detectable individual collagen fibres on a background of grey to pale eosinophilic seroproteinaceous fluid. Intact vascular structures were identified principally deep to the burn area in the collagen. Follicle cell injury was identified by cytoplasmic clearing/swelling and nuclear pyknosis, and these follicular changes were often the deepest evidence of burn injury seen for each time point. Histological scores (epidermal changes) or dermal parameter depths (dermal changes) were regressed on burn contact time. Collagen alteration (r(2) = 0.91) correlated best to burn severity followed by vascular patency (r(2) = 0.82), epidermal changes (r(2) = 0.76), subepidermal vesicle formation (r(2) = 0.74) and follicular cell injury was useful in all but deep burns. This study confirms key morphological parameters can be an important tool for the detection of burn severity in this acute burn model.

Retroperitoneal leiomyosarcoma of the inferior vena cava mimicking a liver tumor.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare sarcoma, but it is the most common primary malignancy of the IVC. It has an extremely poor prognosis. We describe a 60-year-old white female complaining of abdominal fullness for 7 weeks before she sought medical assistance. Initial work-up including sonography, computed tomography, and magnetic resonance showed a tumor in the right upper quadrant of the abdominal cavity originating from the liver with compression of the IVC and displacement of the right kidney. The patient underwent surgical resection of the tumor with clear margins and reconstruction of the IVC using a Dacron tubular graft. Postoperatively, she was placed on Coumadin and adjuvant chemotherapy was started. Subsequently, the patient developed metastasis into the liver and peripancreatic nodes during the follow-up period. Considering the aggressiveness of this tumor, early radical en block resection with clear margins is still the only chance for long-term survival.

Repetitive ischemia-reperfusion injury: a plausible mechanism for documented clinical burn-depth progression after thermal injury.

Our previous studies confirmed the phenomenon of burn depth progression despite adequate Parkland formula resuscitation [Kim et al. J Burn Care Rehabil 2001;22960:406-6]. Repetitive ischemia-reperfusion injury (I-R) is a plausible explanation and is suggested by the concomitant swings we have observed in serum base deficit (BD) during resuscitation from burn shock. We chose to explore whether laser Doppler imaging (LDI) evidence of burn depth progression mirrored cycles of I-R (episodic swings in continuously measured BD). Positive findings would support the hypothesis that repetitive episodes of I-R is a factor in burn depth progression despite apparently adequate resuscitation. A total of 14 patients with severe life-threatening burns (median 51% TBSA) underwent continuous BD monitoring using a Paratrend 7 (Malvern PA) during 48 hours of resuscitation. Fluid needs were estimated using the Parkland formula, then were titrated to urine output. The slopes of BD changes were then analyzed. Worsening of BD greater than 0.2 mmol/l/min was noted, and a proportion derived relative to pooled data on 5-minute intervals. In four of the patients, LDI scans were performed on six representative areas sequentially every 4 hours. The analysis of median flux in these LDI images provided real-time determination of burn depth progression. Eight patients eventually died. Only four patients achieved a normal BD within 12 hours of monitoring despite exceeding the Parkland formula estimate and meeting urinary output parameters. Our analysis also showed cyclical peaks and valleys in the BD curve (P < .001), suggesting repetitive I-R insults. All increases in BD preceded changes that could be detected in vital signs or urine output. Finally, LDI confirmed that the burn depths continued to progress despite apparently adequate resuscitation, and also showed that there are similar peaks and valleys in the perfusion of the wounds (P < .0001), which mimic the changes in the BD curve. Responses to fluid resuscitation do not follow a linear pattern in the case of massive burns. These results in repetitive periods of tissue hypoperfusion evidenced by BD alterations and may contribute to progressive deepening of the burn wound.

Seven years' experience with Integra as a reconstructive tool.

The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro, NJ) was developed and has been widely used as primary coverage for excised acute burns. Our take has been slightly different, finding it most useful in the management of complex soft-tissue loss and threatened extremities as the result of tendon, joint, or bone exposure. Often tasked to fill significant volume loss, we have become adept at stacked multiple-layer applications. Creative use of this material has resulted in unexpected successes with distal limb salvage; the technique takes its place beside adjacent tissue transfer, composite flaps, and vascular pedicle flaps in our burn reconstructive practice. A prospective registry (44 patients) has been kept during the past 7 years that catalogs wounds with complex soft-tissue loss treated with Integra grafts. Many of these patients were at risk of extremity loss because of exposed tendons, joints, or bone. Integra was applied after 1:1 meshing. With profound soft-tissue defects, multiple layers of Integra were serially applied 1 to 2 weeks apart for reconstitution of soft-tissue contours. Local Integra graft infections were managed by silicone unroofing followed by topical sulfamylon liquid dressings. Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper envenomations, and total abdominal wall avulsion in one patient after being run over by a bus. Patients generally were free of pain from their wounds during the maturation phase of the Integra neodermis. Restoration of tissue contour was significantly better when using multiple layers for deep defects. Second and third layers of Integra were successfully applied after an abbreviated first graft maturation period of 7 days. Epithelial autografts on multilayer Integra applications frequently "ghosted"; they would auto-digest to dispersed cells followed subsequently by the reappearance of a confluent epithelial layer. Final grafted skin morphology over palmar and plantar surfaces assumed the type and fingerprint pattern of the original tissues. Infections were readily visible. Early recognition kept them to easily treated circumscribed areas, which did not jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but not significantly greater than with traditional techniques. The specific reconstructive use of Integra permitted unexpected salvage of several threatened extremities by protecting exposed tendons, bones and joints. Long-term histologic examination revealed unexpected persistence of Integra collagen. Large volume loss wounds benefited from the ability to fill voids with multilayered applications.