The effect of pulsatile pump perfusion on hepatitis C transmission in kidney transplantation: A prospective pilot study.

With increasing utilization of hepatitis C (HCV) viremic donor organs, there may be a role for kidney pump perfusion to reduce viral load and prevent HCV transmission. We performed a prospective pilot study of HCV viremic donors; one kidney from each donor pair was pumped with perfusate exchanges and viral load testing at least every 4 hours. Donor, recipient, and transplant characteristics were obtained with clinical outcomes. Linear regression was performed to quantify the association between pump time and perfusate viral load. Six HCV viremic donors for six pairs of aviremic recipients were included. Perfusate of the pumped kidneys showed detectable virus throughout the pump cycles. Although perfusate viral levels decreased with increasing pump times, this was not statistically significant (ß = -.48, P = .36). All recipients had detectable HCV RNA postoperatively. The pumped cohort had an insignificantly reduced mean viral load compared to pumped recipients (1352 ± 2006 vs 26 170 ± 61 211, P = .09). Time to initiation of direct-acting antiviral was 32 ± 12 vs 26 ± 7 days (P = .17) and to undetectable levels was 66 ± 27 vs 55 ± 22 days (P = .82) for the pumped and unpumped cohorts, respectively. Pulsatile perfusion alone does not appear adequate to decrease HCV transmission. Future studies will need to explore additional ex vivo interventions to pumping.

The impact of antibodies and virtual crossmatching on intestinal transplant outcomes.

PURPOSE OF REVIEW: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies. RECENT FINDINGS: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes. Most have reported associations between DSA presence and rejection-related graft failure. The evolution of antibody detection methods and improvements in crossmatch testing have allowed for a systematic approach to the broadly sensitized transplant candidate, and facilitated the identification of compatible organ donors. The virtual crossmatch can be used to aid in organ allocation and avoid transplantation across preformed DSA. However, much remains unknown about the mechanisms of antibody-mediated injury in the intestinal graft, and the effectiveness of current therapies against DSA has yet to be established. SUMMARY: On the basis of available data, we will provide recommendations for the testing and management of DSA among intestinal transplant recipients. The precise management protocol should be tailored to each individual based on immunologic risk as well as clinical status.

BH3-only proteins contribute to steatotic liver ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion injury (IRI) to the liver continues to be a source of significant morbidity, especially in patients with hepatic steatosis. This is a growing problem given the increase in nonalcoholic fatty liver disease. B-cell lymphoma-2 homology3-only members of the B-cell lymphoma-2 protein family are known mediators of cellular apoptosis, although their role in hepatic IRI is still emerging. The goal of this study was to investigate the effect of Bim and Bid on warm hepatic IRI in the setting of steatosis. METHODS: Lean and obese Bim and/or Bid wild-type (WT) and double knockout (DKO) mice underwent 60 min of warm hepatic ischemia using a 70% segmental occlusion technique. Obesity and hepatic steatosis were induced using a high fat diet. Hepatocellular injury patterns were compared among lean and steatotic mice after reperfusion. Differences were analyzed using a Student t-test and reported as mean ± standard error of the mean. RESULTS: DKO mice were protected from IRI relative to WT. A high fat diet created equal degrees of steatosis in both WT and DKO mice. The IRI was increased in steatotic WT livers; however, DKO mice remained protected relative to WT despite hepatic steatosis. CONCLUSIONS: The B-cell lymphoma-2 homology3-only proteins are important mediators of hepatic IRI in both lean and steatotic livers. These mechanisms have been underappreciated in steatotic liver injury and may be leveraged as targets for intervention in clinical scenarios such as transplant and hypovolemic shock.

Incisional Hernia Development after Live Donor Nephrectomy: Impact of Surgical Technique.

BACKGROUND: Characteristics of incisional hernia (IH) formation after live donor nephrectomy (LDN) are not well-defined. The goal of this study was to describe the incidence of IH within 3 years after LDN and identify risk factors contributing to their formation. METHODS: We performed a single-center, retrospective review of all LDN between February 2013 and October 2018. Patients with and without IH were compared based on donor and operative variables. Data were analyzed using chi-square tests with column proportions. Multivariable logistic regression with backward elimination was used to evaluate the likelihood of IH on the basis of potential risk factors. RESULTS: Three hundred one individuals underwent live donor nephrectomy. Twenty-eight patients (9.3%) developed an IH, with a median time to development of 7 months (range: 2-24 months). Obesity (body mass index ≥30), periumbilical hand port, and vertical infraumbilical hand port were associated with increased risk of IH development on univariate analysis. On multivariate analysis, obesity and periumbilical hand port location were persistent risk factors for IH. CONCLUSIONS: The incidence of IH after LDN is prevalent and associated with obesity and operative technique. Placing the hand port infraumbilical with a transverse fascial incision may reduce the risk of IH after LDN.

Novel three-dimensional imaging technique improves the accuracy of hepatic volumetric assessment.

BACKGROUND: With pre-operative prediction of liver volume becoming increasingly important to safely carry out complex hepatic resections, the aim of the present study was to validate the accuracy of a three-dimensional (3-D) liver surgery operative planning software in performing hepatic volumetry. METHODS: Between 1999 and 2007, we performed 29 live donor liver resections for transplantation. Eleven patients had pre-operative volumetry performed by radiologists from either computed tomography (CT) or magnetic resonance (MR) imaging with documentation of the corresponding specimen weight. Retrospectively, images were uploaded into Scout™ where 3-D models of each case were generated to perform volumetry. A correlational analysis was performed followed by an accuracy comparison. RESULTS: Estimations by both radiologists and Scout™ were significantly correlated with the specimen weights, P ≤ 0.0001. Compared with radiologists' volumetry, Scout™ significantly improved overall accuracy [per cent error (PE) 20.0% ± 5.3 vs. 32.9% ± 5.7, P=0.005], accuracy of CT-based estimations (PE 23.2% ± 6.7 vs. 37.2% ± 6.9, P=0.023) and accuracy of the left lateral section (PE 11.1% ± 3.9 vs. 26.6% ± 6.8, P=0.027). DISCUSSION: This 3-D planning software is a valid tool for use in volumetry. Significance is greatest for CT-based models of the left lateral section. This approach gives surgeons the ability to assess volumetrics and actively plan resections.

Hepatocellular carcinoma: a review of the surgical approaches to management.

Hepatocellular carcinoma (HCC) is increasing in incidence in the United States and is strongly associated with chronic liver disease and cirrhosis. Surgical therapy with liver transplantation or resection remains the mainstay of curative therapy for patients with HCC. Therapeutic decisions in patients with HCC are complex and are best approached via a multidisciplinary group of liver transplant and hepatobiliary surgeons, oncologists, and hepatologists. In this manuscript, we review the current surgical management of HCC.

Impact of Social Media on Self-Referral Patterns for Living Kidney Donation.

Background: As the organ-shortage crisis continues to worsen, many patients in need of a kidney transplant have turned to social media to find a living donor. The effect of social media on living kidney donation is not known. The goal of this study is to investigate the influence of social media on those interested in donating a kidney. Methods: Self-referrals for living kidney donation from December 2016 to March 2019 were retrospectively reviewed. Age, sex, race, and relationship of individuals petitioned through social media (SM) were compared with those petitioned through verbal communication (VC). Data were analyzed using chi-squared tests, with z tests of column proportions, and multivariable logistic regression. Results: A total of 7817 individuals (53% SM, 36% VC, and 10% other) were self-referred for living kidney donation. The analysis sample included 6737 adults petitioned through SM (n=3999) or VC (n=2738). Half (n=3933) of the individuals reported an altruistic relationship, and 94% of these respondents were petitioned through SM. Although univariate analyses indicated that SM respondents were younger, more likely female, more likely White, and more likely to have directed altruistic intent than those petitioned through VC (all P<0.05), multivariable logistic regression demonstrated that only decreased age, female sex, and relationship were significantly related to likelihood of SM use (all P<0.001). Conclusions: The use of SM to petition living kidney donors is prevalent and accounts for a greater proportion of respondents compared with VC. SM respondents tend to be younger, female, and altruistic compared with VC. Directed altruistic interest in kidney donation is almost exclusively generated through SM.

Intestinal failure after bariatric surgery: Treatment and outcome at a single-intestinal rehabilitation and transplant center.

BACKGROUND: Though intestinal failure (IF) after bariatric surgery (BS) is uncommon, its prevalence is increasing. However, data on the outcomes for these patients are limited. OBJECTIVES: To analyze the outcomes of treatment for patients with IF after BS. SETTING: University hospital. METHODS: A single-center analysis (1991-2016) of outcomes according to treatment arms established by a multidisciplinary team. RESULTS: Twenty-five IF patients were identified (median age 45 yr). BS was 92% Roux-en-Y gastric bypass. The major cause of IF was volvulus/internal hernia (72%). Median time from BS to IF was 48 months. Treatment arms were intestinal rehabilitation (IR, n = 15), transplantation (TXP, n = 5), and parenteral nutrition (PN, n = 5). For IR, median bowel length was 60 cm. Forty-six percent ultimately discontinued PN. Twenty-seven percent were partially weaned PN and 27% failed IR. Common surgical rehabilitation was Roux-en-Y gastric bypass reversal and restoration of gastrointestinal continuity. The 5-year overall survival was 74%. For TXP, 7 patients were listed for TXP (5 initially and 2 after failed IR). Three underwent TXP, 2 isolated intestine and 1 isolated liver. Three were delisted (1 improvement and 2 death). For PN, 6 patients required long-term PN (5 initially and 1 after failed IR). Four patients are alive currently. CONCLUSIONS: IF after BS is an increasing problem facing IR centers. Internal hernia is the major cause. Surgical IR is the first-line therapy and affords the best outcome. TXP is reserved for rescuing patients who failed IR or develop PN complications. Long-term PN is suitable for patients in whom IR or TXP is impractical.

Quantification of hepatic functional capacity: a call for standardization.

Reliable assessments of liver function are becoming increasingly important as more patients with surgically amenable liver disease are considered for treatment. Static markers of liver function are not sufficient to provide accurate assessments of hepatic function in order to risk stratify patients undergoing hepatic resection. Metabolic tests are dynamic indicators of liver function, but can be unreliable under certain conditions and thus difficult to make comparisons. Clearance tests avoid some of the pitfalls encountered during metabolic testing, but depend on hepatic blood flow and say little about hepatocyte function. Testing that combines imaging with measures of hepatocyte uptake may offer the most utility when planning surgical resections.

Extrapleural pneumonectomy complicated by acute superior mesenteric artery syndrome.

We present a patient who developed an acute superior mesenteric artery (SMA) syndrome following pneumonectomy. Although rarely described, a majority of cases develop insidiously from a gradual loss of retroperitoneal fat in the setting of malnourishment. A postoperative presentation is atypical, however procedures that narrow the aortomesenteric angle have been associated with the development of SMA syndrome. This case illustrates an important anatomic relationship that thoracic surgeons performing lung resection surgery should be aware of in order to avoid predisposing patients to SMA syndrome.

Novel in vitro model for studying hepatic ischemia-reperfusion injury using liver cubes.

BACKGROUND: Although inflow occlusion techniques have given surgeons the ability to carry out increasingly complex liver resections, ischemia-reperfusion (IR) injury continues to be a source of morbidity. Efforts to ameliorate IR injury have been hindered in absence of adequate preclinical models. The goal of the present study was to develop a simple, efficient, and cost-effective means of studying hepatic IR injury. METHODS: Liver cubes were procured from normal (C57BL/6) mice. After hepatectomy, 4-mm punch biopsies were taken for individual placement in culture wells containing hepatocyte media. Experimental cubes underwent hypoxia for 60 minutes, whereas controls remained normoxic. Supernatants were collected from individual wells after 0, 6, and 12 hours of rediffusion for transaminase and cytokine measurement. Histologic examination was performed on individual cubes. RESULTS: Extensive histologic injury was seen in the experimental cubes compared with controls with greater staining for activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling at 6 and 24 hours, respectively. Changes consistent with ischemic injury occurred more centrally in liver cubes, whereas markers for rediffusion injury were appreciated along the periphery. Transaminases were significantly higher at 6 hours after rediffusion in experimental cubes compared with controls (P = .02). tumor necrosis factor-α and interleukin-1ß were significantly higher in the media of experimental cubes compared with controls at 12 hours rediffusion (P = .05 and .03 respectively). CONCLUSION: In vitro IR of cubes produces a significant injury with a pattern reflective of hepatic lobular architecture. This novel technique may open new avenues for uncoupling the mechanisms of IR while facilitating rapid screening of potential therapies.

Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma.

OBJECTIVE: To correlate microscopic margin status with survival and local control in a large cohort of patients from a high-volume pancreatic cancer center. DESIGN: Retrospective database review. A uniform procedure for margin analysis was used with 4-color inking (neck, portal vein groove, uncinate, and posterior pancreatic margin) by the surgeon in the operating room. SETTING: A tertiary care hospital. PATIENTS: We reviewed patients who underwent pancreaticoduodenectomy between September 1, 1997, and December 31, 2008, from a prospective, institutional database. MAIN OUTCOME MEASURES: Using Cox regression models, we identified pathologic characteristics associated with local recurrence (LR) after controlling for potential confounding variables. Overall and LR-free survival curves were generated by the Kaplan-Meier method. RESULTS: Of 285 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma, 97 (34.0%) had 1 or more positive microscopic margins (uncinate, 16.5%; portal vein groove, 8.8%; neck, 7.7%; and posterior, 10.5%). A total of 198 patients (69.5%) recurred, with the first site of failure being LR only in 47 (23.7%), local plus distant recurrence in 42 (21.2%), and distant recurrence only in 109 (55.1%). Patients with LR only were significantly more likely to have lymph node involvement (adjusted hazard ratio, 2.66; 95% CI, 1.25-5.63) or a positive posterior margin (adjusted hazard ratio, 4.27; 95% CI, 2.07-8.81). Patients with a positive posterior margin had significantly poorer LR-free survival with (P < .001) or without (P = .01) lymph node involvement. CONCLUSIONS: When systematically assessed, the incidence of positive microscopic margins is high. Positive posterior margins and lymph node involvement were each independently and significantly associated with LR.