Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology. AIM: To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States. METHODS: WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020. RESULTS: Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001). CONCLUSION: During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Trends and outcomes of liver transplantation among older recipients in the United States.

BACKGROUND: The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited. AIM: To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States. METHODS: We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old). RESULTS: Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI. CONCLUSION: While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.

Improving Liver Transplant Outcomes for Hepatitis C Virus Hepatocellular Carcinoma in the Direct-Acting Antiviral Therapy Era.

BACKGROUND: Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS: We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS: HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS: DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.

Successful Management of COVID-19 Infection in 2 Early Post-Liver Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital. CASE DESCRIPTIONS: Two patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery. CONCLUSION: The management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.

A pilot study of letrozole for one year in women at enhanced risk of developing breast cancer: effects on mammographic density.

BACKGROUND: Tamoxifen or raloxifen for 5 years reduces the risk of developing invasive breast cancer by 40%. To address safety concerns and seek enhanced efficacy, studies of new chemopreventive agents using mammographic density as a surrogate end point are attractive. PATIENTS AND METHODS: Postmenopausal women with risk factors for developing breast cancer were given letrozole 2.5 mg daily for one year, and mammographic density was the biomarker of breast cancer risk modification. It was assessed (blinded to the reader) at baseline, 6, and 12 months in 16 evaluable women among 20 enrolled. RESULTS: Eight patients exhibited decreased mammographic density at six months, and eleven at 12 months. Toxicities included joint aches not precluding continued treatment. CONCLUSION: This pilot study supports the use of letrozole for reducing breast cancer risk. In addition, it encourages prospective studies of serial changes in mammographic density as a biomarker of risk modification within a selected high-risk population.

A decade of change: an institutional experience with breast surgery in 1995 and 2005.

INTRODUCTION: With the adoption of routine screening mammography, breast cancers are being diagnosed at earlier stages, with DCIS now accouting for 22.5% of all newly diagnosed breast cancers. This has been attributed to both increased breast cancer awareness and improvements in breast imaging techniques. How have these changes, including the increased use of image-guided sampling techniques, influenced the clinical practice of breast surgery? METHODS: The institutional pathology database was queried for all breast surgeries, including breast reconstruction, performed in 1995 and 2005. Cosmetic procedures were excluded. The results were analysed utilizing the Chi-square test. RESULTS: Surgical indications changed during 10-year study period, with an increase in preoperatively diagnosed cancers undergoing definitive surgical management. ADH, and to a lesser extent, ALH, became indications for surgical excision. Fewer surgical biopsies were performed for indeterminate abnormalities on breast imaging, due to the introduction of stereotactic large core biopsy. While the rate of benign breast biopsies remained constant, there was a higher percentage of precancerous and DCIS cases in 2005. The overall rate of mastectomy decreased from 36.8% in 1995 to 14.5% in 2005. With the increase in sentinel node procedures, the rate of ALND dropped from 18.3% to 13.7%. Accompanying the increased recognition of early-stage cancers, the rate of positive ALND also decreased, from 43.3% to 25.0%. CONCLUSIONS: While the rate of benign breast biopsies has remained constant over a recent 10-year period, fewer diagnostic surgical image-guided biopsies were performed in 2005. A greater percentage of patients with breast cancer or preinvasive disease have these diagnoses determined before surgery. More preinvasive and Stage 0 cancers are undergoing surgical management. Earlier stage invasive cancers are being detected, reflected by the lower incidence of axillary nodal metastases.

Intrahepatic portal cavernoma as an indication for liver transplantation.

Cavernous transformation of the portal vein (portal cavernoma) consists of a periportal or/and intrahepatic venous collateral network, developed as a result of acute or long-standing portal vein thrombosis. Better control of hemorrhagic and thrombotic complications in the patients with portal cavernoma substantially improves their life span and the clinical outcome. However, biliary complications that occur in the late stages of this disease have been recently recognized as challenging management issues because they recur and are difficult to treat. Because of the relatively small number of the patients with cholangiopathy due to portal cavernoma, there is no current standardized treatment approach. We report the case of a predominantly intrahepatic portal cavernoma occurring in a patient with chronic idiopathic portal vein thrombosis, which led to severe cholangiopathy that mimicked primary sclerosing cholangitis and cholangiocarcinoma, was unresponsive to endoscopic stent placement, and finally required liver transplantation.

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.

Bone marrow-derived cells contribute to epithelial engraftment during wound healing.

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (

Scirrhous changes in dysplastic nodules do not indicate high-grade status.

BACKGROUND AND AIMS: Dysplastic nodules (DN) may be divided into high-grade and low-grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high-grade DN, based on the morphological and cell-kinetic analyses using immunohistochemical stains for Ki-67. METHODS: We reviewed 35 livers with DN and selected 15 DN with scirrhous change. We stained DN-bearing sections of each case with hematoxylin and eosin, trichrome, reticulin and Perls' stain. We tried to subclassify and characterize the scirrhous change according to the fibrosis pattern. We also stained with Ki-67 immunohistochemically to assess the proliferative activity of DN with scirrhous change. RESULTS: We found two types of scirrhous change, that is, pericellular and stellate. The pericellular type was related to the Mallory body-forming cholestatic degeneration, whereas the stellate type was associated with extensive portal fibrosis probably induced by ischemic damage. Among DN with scirrhous change, high-grade DN comprised five nodules (33%) and there were 10 (67%) low-grade nodules. There was no significant relationship between the presence or the types of scirrhous change and the grade of DN. The significant differences of Ki-67 labeling indices between types of scirrhous change were not shown in this study. We also could not find the differences between Ki-67 labeling indices of scirrhous DN (high and low grades) and those of surrounding regenerative nodules. CONCLUSIONS: This evidence indicated that the scirrhous change in DN was not a specific feature of high-grade DN. We also found that scirrhous DN have two morphological varieties that may represent biologically different processes, that is, pericellular scirrhous type and stellate scirrhous type.

Transplantation for hepatocellular carcinoma and cirrhosis: sensitivity of magnetic resonance imaging.

The sensitivity of magnetic resonance imaging (MRI) in patients who undergo transplantation for hepatocellular carcinoma (HCC) and cirrhosis is not known. We prospectively evaluated 24 patients with known HCC who underwent MRI and subsequent transplantation within 60 days (mean, 20 days). Using a phased-array coil at 1.5T, breath-hold turbo STIR and T2-weighted MR images were performed. Dynamic gadolinium-enhanced MRI was performed using a two- or three-dimensional gradient echo pulse sequence with images obtained in the hepatic arterial, portal venous, and equilibrium phases. The prospective interpretation of the MR study was directly compared with thin-section pathology evaluation of the explanted livers. All 24 patients had at least one HCC, and MR diagnosed tumor in 21 (88%) of these patients. On a lesion-by-lesion basis, MRI depicted 39 of 118 HCC for an overall sensitivity of 33%. MRI detected five (100%) of five lesions >5 cm, 20 (100%) of 20 lesions >2 cm but not exceeding 5 cm, 11 (52%) of 21 lesions between 1 and 2 cm, and three (4%) of 72 lesions <1 cm. Of the nine patients with carcinomatosis (innumerable lesions less than 1 cm), MR detected three lesions in one patient. Of the 15 dysplastic nodules found at pathology, MRI depicted a single 1.8-cm high-grade lesion, for a sensitivity of 7%. In conclusion, MRI is sensitive for the detection of HCC measuring at least 2 cm in diameter but is insensitive for the diagnosis of small HCC (<2 cm) and carcinomatosis.

Comprehensive MR imaging in the preoperative evaluation of living donor candidates for laparoscopic nephrectomy: initial experience.

PURPOSE: To evaluate the accuracy of magnetic resonance (MR) imaging in the preoperative evaluation of potential living renal donors who are candidates for laparoscopic nephrectomy. MATERIALS AND METHODS: Twenty-eight donor candidates who underwent subsequent laparoscopic nephrectomy were examined by using a torso phased-array coil at 1.5 T. Gadolinium-enhanced MR angiograms, MR venograms, and MR urograms were obtained in all patients by using an interpolated three-dimensional T1-weighted spoiled gradient-echo sequence (3.4-6.8/1.2-2.3 [repetition time msec/echo time msec], 25 degrees -40 degrees flip angle). Interpretation of the MR images was used to assess the arterial, venous, and ureteral anatomy, as well as parenchymal masses and scarring, and findings were compared with the surgical findings in all patients. Statistical evaluation was performed, with the surgical findings as the reference standard. RESULTS: At MR imaging, 31 of 32 renal arteries and one of three early-branching arteries were identified correctly. The correct venous anatomy was identified in 23 of 28 patients, including a single left renal vein anterior to the aorta (n = 16), retroaortic left renal vein (n = 2), circumaortic left renal vein (n = 2), and single right renal vein (n = 3). A single collecting system in all harvested kidneys was identified correctly with MR urography. Overall, MR imaging correctly depicted vascular, ureteral, and parenchymal anatomy in 21 of 28 patients. Twenty-seven of 28 patients underwent successful laparoscopic donor nephrectomy on the basis of the MR findings. One procedure was converted to open nephrectomy on the basis of complex venous anatomy not prospectively identified on the MR images. The sensitivity and positive predictive value of MR imaging in correctly determining the combined vascular, ureteral, and parenchymal anatomy in the harvested kidney were 75% (21 of 28) and 95% (21 of 22), respectively. CONCLUSION: Comprehensive gadolinium-enhanced MR imaging can depict the vascular anatomy, collecting system, and renal parenchyma preoperatively in patients who are candidates for laparoscopic living-donor nephrectomy.