What Should I Do?

: The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.

How important is social support in determining patients' suitability for transplantation? Results from a National Survey of Transplant Clinicians.

BACKGROUND: National guidelines require programmes use subjective assessments of social support when determining transplant suitability, despite limited evidence linking it to outcomes. We examined how transplant providers weigh the importance of social support for kidney transplantation compared with other factors, and variation by clinical role and personal beliefs. METHODS: The National survey of the American Society of Transplant Surgeons and the Society of Transplant Social Work in 2016. Using a discrete choice approach, respondents compared two hypothetical patient profiles and selected one for transplantation. Conditional logistic regression estimated the relative importance of each factor; results were stratified by clinical role (psychosocial vs medical/surgical providers) and beliefs (outcomes vs equity). RESULTS: Five hundred and eighy-four transplant providers completed the survey. Social support was the second most influential factor among transplant providers. Providers were most likely to choose a candidate who had social support (OR=1.68, 95% CI 1.50 to 1.86), always adhered to a medical regimen (OR=1.64, 95% CI 1.46 to 1.88), and had a 15 years life expectancy with transplant (OR=1.61, 95% CI 1.42 to 1.85). Psychosocial providers were more influenced by adherence and quality of life compared with medical/surgical providers, who were more influenced by candidates' life expectancy with transplant (p<0.05). For providers concerned with avoiding organ waste, social support was the most influential factor, while it was the least influential for clinicians concerned with fairness (p<0.05). CONCLUSIONS: Social support is highly influential in listing decisions and may exacerbate transplant disparities. Providers' beliefs and reliance on social support in determining suitability vary considerably, raising concerns about transparency and justice.

The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant.

CONTEXT: Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. OBJECTIVES: To develop a scoring system to stratify risk of alcohol relapse after liver transplant. DESIGN: Retrospective medical record review. SETTING AND PARTICIPANTS: All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. MAIN OUTCOME MEASURE: The incidence of return to any alcohol consumption after liver transplant. RESULTS: Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. CONCLUSION: Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.

A comparison of surgical outcomes for noncirrhotic and cirrhotic hepatocellular carcinoma patients in a Western institution.

BACKGROUND: Although cirrhosis is common among Western hepatocellular carcinoma (HCC) patients, a substantial proportion are not cirrhotic. Studies examining surgical outcomes in noncirrhotic patients primarily evaluate Asian populations and liver resections. We describe cirrhotic and noncirrhotic HCC patients undergoing resection and transplantation at a Western institution. METHODS: We retrospectively reviewed 188 HCC patients treated surgically from 2000 to 2011 at a single Western institution. The primary endpoint was recurrence. Secondary endpoints included time to recurrence and overall survival. RESULTS: We evaluated 138 cirrhotic and 50 noncirrhotic patients with a median follow-up of 33.8 months. Noncirrhotics mostly underwent liver resection (90%), whereas cirrhotics primarily underwent transplantation (67%). Hepatitis B was the most common underlying liver disease for noncirrhotics (64%), whereas hepatitis C (55%) and alcohol abuse (32%) predominated among cirrhotics. Pathologic evaluation demonstrated tumors in noncirrhotics that were fewer in number, larger, less differentiated, and more likely to have vascular invasion. Recurrence was more common for noncirrhotics (36 vs. 18%; P = .008) and more common after resection compared with transplantation. Overall median survival was 46.9 months for both groups. After resection, noncirrhotics had longer survival times than did cirrhotics (41.6 vs. 32.9 months; P = .04). Vascular invasion was an independent predictor for recurrence; tumor size was a predictor of mortality. CONCLUSION: Noncirrhotics in our Western cohort had higher risk pathologic features, more frequently underwent resection, and suffered more recurrences than did cirrhotics. Overall survival was similar for both groups. Prospective studies of noncirrhotic HCC patients in Asia and Western countries may inform surveillance and treatment.

Failure of fibrotic liver regeneration in mice is linked to a severe fibrogenic response driven by hepatic progenitor cell activation.

Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed in C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced liver fibrosis. Liver function and regeneration was monitored at 1 to 14 days thereafter by assessing liver mass, alanine aminotransferase (ALT), mRNA expression, and histology. Progenitor (oval) cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and TWEAK-neutralizing antibody were used to manipulate progenitor cell proliferation in vivo. In fibrotic liver, hepatocytes failed to replicate efficiently after PHx. Fibrotic livers showed late (day 5) peak of serum ALT (3542 ± 355 IU/L compared to 93 ± 65 IU/L in nonfibrotic livers), which coincided with progenitor cell expansion, increase in profibrogenic gene expression and de novo collagen deposition. In fibrotic mice, inhibition of progenitor activation using TWEAK-neutralizing antibody after PHx resulted in strongly down-regulated profibrogenic mRNA, reduced serum ALT levels and improved regeneration. Failure of hepatocyte-mediated regeneration in fibrotic liver triggers activation of the progenitor (oval) cell compartment and a severe fibrogenic response. Inhibition of progenitor cell proliferation using anti-TWEAK antibody prevents fibrogenic response and augments fibrotic liver regeneration. Targeting the fibrogenic progenitor response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis.

A simultaneous liver-kidney transplant recipient with IgA nephropathy limited to native kidneys and BK virus nephropathy limited to the transplant kidney.

Immunoglobulin A (IgA) deposition in the native kidneys of patients with liver disease is well described. Secondary IgA nephropathy usually is thought to be benign, but hematuria, proteinuria, and loss of kidney function have been reported in this context. BK virus nephropathy is an important cause of kidney transplant loss; however, BK virus nephropathy is rare in the native kidneys of patients who underwent transplantation of other organs. We report the case of a patient with alcohol-related end-stage liver disease and chronic kidney disease with hematuria who underwent simultaneous liver-kidney transplantation. His kidney function decreased over the course of several weeks posttransplantation. Biopsy of the transplant kidney showed BK virus nephropathy, but no IgA deposits. In contrast, biopsy of the native kidneys showed IgA deposits, but no BK virus nephropathy. To our knowledge, this is the first reported case of a simultaneous liver-kidney transplantation wherein both the native and transplant kidneys were biopsied posttransplantation and showed exclusively different pathologies. These findings confirm the predilection of BK virus nephropathy for transplant rather than native kidneys.

Surgical complications in 275 HIV-infected liver and/or kidney transplantation recipients.

BACKGROUND: In this report, we examine the surgical safety and complications (SC) among 125 liver (L) and 150 kidney (K) HIV+ transplantation (TX) recipients in a prospective nonrandomized U.S. multicenter trial. METHODS: Subjects were required to have CD4+ T-cell counts >200/100 cells/mm3 (K/L) and undetectable plasma HIV-1 RNA (Viral Load [VL]) (K) or expected posttransplantation suppression (L). Impact of SCs (N ≥ 7) was evaluated by use of the proportional hazards models. Baseline morbidity predictors for SCs (N ≥ 7) were assessed in univariate proportional hazards models. RESULTS: At median 2.7 (interquartile range 1.9-4.1) and 2.3 (1.0-3.7) years after TX, 3-month and 1-year graft survival were [K] 96% (95% CI 91%-98%) and 91% (95% CI 85%-94%) and [L] 91% (95% CI 85%-95%) and 77% (95% CI 69%-84%), respectively. A total of 14 K and 28 L graft losses occurred in the first year; 6 K and 11 L were in the first 3 months. A total of 26 (17%) K and 43 (34%) L experienced 29 and 62 SCs, respectively. In the liver multivariate model, re-exploration was marginally associated (hazard ratio [HR] 2.8; 95% CI 1.0-8.4; P = .06) with increased risk of graft loss, whereas a greater MELD score before transplantation (HR 1.07 per point increase; 95% CI: 1.01-1.14; P = .02), and detectable viral load before TX (HR 3.6; 95% CI 0.9-14.6; P = .07) was associated with an increased risk of wound infections/dehiscence. CONCLUSION: The rates and outcomes of surgical complications are similar to what has been observed in the non-HIV setting in carefully selected HIV-infected liver and kidney TX recipients.

The Seville expert workshop for progress in posttransplant lymphoproliferative disorders.

: Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein-Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD.

Carbon monoxide enhances early liver regeneration in mice after hepatectomy.

Hepatocyte proliferation early after liver resection is critical in restoring liver mass and preserving function as the liver regenerates. Carbon monoxide (CO) generated by heme oxygenase-1 (HO-1) strongly influences cellular proliferation and both HO-1 and CO are accepted hepatoprotective molecules. Mice lacking functional HO-1 were unable to mount an appropriate regenerative response following partial hepatectomy (PHTx) compared to wildtype controls. We therefore hypothesized that exogenous administration of CO at low, nontoxic concentrations would modulate hepatocyte (HC) proliferation and liver regeneration. Animals treated with a low concentration of CO 1 hour prior to 70% hepatectomy demonstrated enhanced expression of hepatocyte growth factor (HGF) in the liver compared to controls that correlated with a more rapid onset of HC proliferation as measured by phospho-histone3 staining, increased expression of cyclins D1 and E, phosphorylated retinoblastoma, and decreased expression of the mitotic inhibitor p21. PHTx also increased activation of the HGF receptor c-Met, which was detected more then 9 hours earlier in the livers of CO-treated mice. Blockade of c-Met resulted in abrogation of the CO effects on HC proliferation. Corresponding with increased HC proliferation, treatment with CO maintained liver function with normal prothrombin times versus a 2-fold prolongation in controls. In a lethal 85% PHTx, CO-treated mice showed a greater survival rate compared to controls. In vitro, CO increased HGF expression in hepatic stellate cells, but not HC, and when cocultured together led to increased HC proliferation. In summary, we demonstrate that administration of exogenous CO enhances rapid and early HC proliferation and, importantly, preserves function following PHTx. Taken together, CO may offer a viable therapeutic option to facilitate rapid recovery following PHTx.

Impact of substance abuse on access to renal transplantation.

BACKGROUND: With an ever-increasing demand for kidneys and limited supply pool, it is essential to understand the balance between utility and equity in transplant access. The goal of this project was to evaluate the association between recipient's substance abuse and renal transplant access in patients with end-stage renal disease (ESRD). METHODS: We used data from the United States Renal Data System. The primary variables of interest were abuse of alcohol, tobacco, or illicit drugs based on information from Centers for Medicare & Medicaid Services form 2728. We analyzed three outcomes in Cox model: (1) being placed on the waiting list for renal transplantation or transplanted (whichever occurred first); (2) first transplant in patients who were placed on the waiting list; and (3) graft loss or mortality after transplant. In addition, we performed subgroup analysis based on age, race, sex, diabetic status, and donor type. RESULTS: We analyzed 1,077,699 patients (age of ESRD onset 62.9±15.5 years, 54.1% males, 64.2% white, and 29.7% African American). When compared with those with no substance abuse, abusing all three substances was associated with reduced transplant access (hazard ratio 0.39, P<0.001 for wait listing/transplant; hazard ratio 0.67, P=0.019 for transplant). This trend was similar in most subgroups studied. CONCLUSION: We demonstrated that patients with ESRD abusing or dependent on tobacco, alcohol, or illicit drugs are less likely to be placed on the waiting list for kidney transplant; and once on the list are less likely to be transplanted. The possible utility justifications for such disparity and potential interventions are discussed.

Increasing time delay from presentation until surgical referral for hepatobiliary malignancies.

BACKGROUND: Studies have shown that delayed treatment of several non-hepatobiliary (HB) malignancies is associated with adverse effects on disease progression and survival. Delayed treatment of HB malignancies has not been thoroughly investigated. METHODS: We performed a retrospective institutional review of patients referred to the Hepatobiliary Surgery Service at Beth Israel Deaconess Medical Center (BIDMC) for hepatobiliary malignancies from 2002 to 2008. Primary outcomes included the time delays (TD) in patient workup. Secondary outcomes were reasons for delay as well as disparities in TD based on demographic factors. RESULTS: Multivariate-adjusted linear regression showed a significant trend of increasing time from presentation until referral to a HB surgeon over the 7-year period (P= 0.001). There were no differences in TD by gender, age or education level. Multivariate-adjusted linear regression showed a significant trend of increasing number of imaging tests performed prior to referral [computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound and endoscopic ultrasound (US/EUS)] (P < 0.001). Multivariate-adjusted linear regression in resectable patients showed a significant difference in overall length of survival in those with a TD1 > 30 days compared with those with a TD1 (TD from presentation until referral) <30 days (P = 0.042). CONCLUSIONS: Delays were associated with an increase in imaging studies and delays adversely affect survival in resected patients. Referring physicians are encouraged to expedite the evaluation and early referral of all patients to an HB surgeon for evaluation and treatment.

Pancreatic adenocarcinoma in the pregnant patient: a case report and literature review.

Pancreatic cancer is the fifth most common cause of cancer-related death in the USA. However, the antepartum diagnosis of pancreatic adenocarcinoma in the pregnant patient is exceedingly rare, with only six cases previously reported in the literature. Optimizing both maternal and fetal health outcomes is particularly challenging when surgical procedures are necessary for staging and/or therapeutic purposes--as these interventions often pose significant risks to both the mother and the developing fetus. In this article, we report a case of pancreatic adenocarcinoma diagnosed during pregnancy and review the literature on the management issues confronted in this unique clinical situation.

Deceased donors with a past history of malignancy: an organ procurement and transplantation network/united network for organ sharing update.

Approximately 2% of deceased donor organ transplants result from donors with a past history of cancer. An analysis of Organ Procurement and Transplantation Network/United Network for Organ Sharing data on 39,455 deceased donors from 2000 to 2005 showed 1069 donors had a PHC, resulting in 2508 transplants, including 1236 kidneys, 891 livers, 199 hearts, 100 lungs, and 82 miscellaneous organs. The most common type of previous cancer in the donor was nonmelanoma skin cancer (n=776) followed by central nervous system malignancies (n=642) and carcinoma of the uterine cervix (n=336). One donor with a glioblastoma multiforme transmitted fatal tumors to three recipients. One donor with a history of melanoma 32 years earlier transmitted a fatal melanoma to a single recipient and, therefore, donors with a history of melanoma should not be used. Donors with a past history of cancer who have a nontraumatic cerebral hemorrhage cause concern because this hemorrhage may be the result of an unrecognized metastatic tumor.

Intraoperative margin re-resection for colorectal liver metastases.

OBJECTIVE: Evaluate recurrence and survival in patients who underwent intraoperative margin re-resection for colorectal cancer liver (CRC) metastases. DESIGN: Retrospective analysis. SETTING: University Hospital, Cincinnati, Ohio. Academic medical center. PARTICIPANTS: Cohort of 118 patients who underwent resection of CRC liver metastases between 1992 and 2004. All patients were divided into 3 groups: resection margin (MOR) less than 1 cm (n = 64), MOR greater than 1 cm (n = 33), and re-resection margin (re-MOR) greater than 1 cm (n = 21). RESULTS: Patients with a margin greater than 1 cm, when compared with re-MOR greater than 1 had decreased incidence of liver and distant recurrence (p < 0.05) as well as improved disease-free survival (39.2 vs 22.9 months, p = 0.023). Differences in overall survival (58.6 vs 44.2 months, p = 0.14) were not significant. CONCLUSION: Intraoperative re-resection is associated with an increased risk of local and distant recurrence, which may be a reflection of both inadequate surgery and underlying tumor biology.