Survival following liver transplantation for locally advanced, unresectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has previously been considered a contraindication to liver transplantation (LT). However, recent series showed favorable outcomes for LT after neoadjuvant therapy. Our center developed a protocol for neoadjuvant therapy and LT for patients with locally advanced, unresectable iCCA in 2010. Patients undergoing LT were required to demonstrate disease stability for 6 months on neoadjuvant therapy with no extrahepatic disease. During the study period, 32 patients were listed for LT and 18 patients underwent LT. For transplanted patients, the median number of iCCA tumors was 2, and the median cumulative tumor diameter was 10.4 cm. Patients receiving LT had an overall survival at 1-, 3-, and 5-years of 100%, 71%, and 57%. Recurrences occurred in seven patients and were treated with systemic therapy and resection. The study population had a higher than expected proportion of patients with genetic alterations in fibroblast growth factor receptor (FGFR) and DNA damage repair pathways. These data support LT as a treatment for highly selected patients with locally advanced, unresectable iCCA. Further studies to identify criteria for LT in iCCA and factors predicting survival are warranted.

Development and implementation of an electrolyte replacement protocol in the outpatient oncology infusion centers of a large academic healthcare system.

BACKGROUND: Patients receiving chemotherapy frequently experience electrolyte imbalances. Electrolyte replacement is, therefore, a necessity as patients may experience life-threatening symptoms.Study objective: The objective of this study was to evaluate the occurrence of low serum potassium and magnesium, and identify the rate of replacement for patients with low serum potassium and magnesium levels. Based on our findings, we developed and implemented a nursing-driven electrolyte replacement protocol. METHODS: Preimplementation phase - A retrospective review for serum potassium and magnesium values obtained during infusion clinic visit between 1 August and 31 October 2016 was conducted. Implementation phase - A nursing-driven electrolyte replacement protocol with medication order "smart-set" and order selection intelligence within EPIC Beacon was developed and implemented in May 2017. Postimplementation phase - The postimplementation phase data were collected from 1 August to 30 November 2017 using a similar approach as the preimplementation phase. RESULTS: Preimplementation phase - During the preimplementation phase of the study, a total of 1495 serum potassium levels and 1193 serum magnesium levels were obtained. Among the 152 patients who needed potassium replacement, 34% (n = 52) were replaced and among the 118 serum magnesium levels that needed replacement, 30% (n = 35) were replaced. Postimplementation phase - 3979 serum potassium and 2707 magnesium levels were obtained. Among the 170 patients who needed potassium replacement, 75% (n = 127) were replaced. Among the 142 patients who needed magnesium replacement, 73% (n = 104) were replaced. CONCLUSION: A 121% increase in potassium replacement and a 143% increase in magnesium replacement were identified after implementing this protocol.

Transplant Oncology: An Emerging Discipline of Cancer Treatment.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.

Transarterial Chemoembolization (TACE) Plus Sorafenib Compared to TACE Alone in Transplant Recipients with Hepatocellular Carcinoma: An Institution Experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The most recent trials of the TACE plus sorafenib combined therapy in patients with unresectable HCC have yielded inconsistent outcomes. The purpose of this study was to compare the outcomes of HCC patients treated with the TACE sorafenib combination as opposed to TACE monotherapy. METHODS: This retrospective study included all patients with unresectable HCC who underwent liver transplantation and were treated by either TACE alone or TACE plus sorafenib between July 2008-December 2019. Demographic and clinical data as well as HCC recurrence post-liver transplant (LT) were reported as frequencies and proportions for categorical variables and as the median and interquartile range (IQR) or mean. Chi-square or Fisher's exact tests were performed for categorical variables and the Kruskal-Wallis test or unpaired test was performed for continuous variables. Kaplan-Meier curves present overall patient survival and HCC-free survival. RESULTS: A total of 128 patients received LT, with a median (IQR) age of 61.4 (57.0, 66.3) years; most were males (77%). Within the TACE-only group, 79 (77%) patients met the Milan criteria and 24 (23%) were beyond the Milan criteria, while the TACE plus sorafenib group had a higher proportion of patients beyond the Milan criteria: 16 (64%) vs. 9 (36%); p = 0.01. The five-year disease-free survival (DFS) between the treatment groups approached significance, with 100% DFS in the TACE plus sorafenib group vs. 67.2% in the TACE-alone group, p = 0.07. Five-year patient survival was 77.8% in the TACE plus sorafenib group compared to 61.5% in the TACE-alone group (p = 0.51). However, in patients who met the beyond Milan criteria, those who received TACE alone had a lower average amount of (percent) tumor necrosis on explant pathology (43.8% ± 32%) compared to patients who received TACE plus sorafenib (69.6% ± 32.8%, p = 0.03). CONCLUSION: This study identified that using TACE plus sorafenib is generally well-tolerated and demonstrated improved overall survival compared to TACE only in transplant recipients with unresectable HCC. A multi-center and prospective randomized controlled trial is needed to substantiate these findings.

Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Metastatic colorectal carcinoma to the right atrium: a case report and review of the literature.

BACKGROUND: Cardiac metastasis due to colon cancer is extraordinarily uncommon. Given the rarity of diagnosis, there is paucity of evidence and hence, no established guidelines for evaluation or clinical management strategy. CLINICAL PRESENTATION: We present the case of a 59 year old male with a previously treated colonic carcinoma who presented with new onset exertional dyspnea. He was noted to be having a right atrial mass on an echocardiogram performed at his cardiologist's office. Further workup with CT angiogram of the chest confirmed a right atrial mass measuring 4.0 cm. Serum CEA was normal. Biopsies of the right atrial mass demonstrated metastatic moderately differentiated colonic adenocarcinoma. Mismatch repair protein expression analysis by immunohistochemistry showed no loss of MLH1, MSH2, MSH6 or PMS2 expression. Next generation sequencing for RAS and BRAF mutations was negative. Patient received treatment with FOLFIRINOX/ bevacizumab with noted reduction in size of mass. CONCLUSION: To the best of our knowledge, this is the first report of next generation sequencing results available on a biopsy of metastatic colorectal cancer to the heart with the largest literature review of 31 reported cases of metastatic colorectal cancer to the heart. It will help direct clinical management and also adds evidence to the potential efficacy of treatment of this rare aggressive disease with chemotherapy in combination with VEGF inhibitors.

Transplant Oncology: An Evolving Field in Cancer Care.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients' survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.

Analysis of the Implementation of Telehealth Visits for Care of Patients With Cancer in Houston During the COVID-19 Pandemic.

PURPOSE: The purpose of this study was to evaluate the use of telemedicine amid the SARS-CoV-2 pandemic in patients with cancer and assess barriers to its implementation. PATIENTS AND METHODS: Telehealth video visits, using the Houston Methodist MyChart platform, were offered to patients with cancer as an alternative to in-person visits. Reasons given by patients who declined to use video visits were documented, and demographic information was collected from all patients. Surveys were used to assess the levels of satisfaction of treating physicians and patients who agreed to video visits. RESULTS: Of 1,762 patients with cancer who were offered telehealth video visits, 1,477 (83.8%) participated. The patients who declined participation were older (67.7 v 60.2 years; P < .0001), lived in significantly lower-income areas (P = .0021), and were less likely to have commercial insurance (P < .0001) than patients who participated. Most participating patients (92.6%) were satisfied with telehealth video visits. A majority of physicians (65.2%) were also satisfied with its use, and 74% indicated that they would likely use telemedicine in the future. Primary concerns that physicians had in using this technology were inadequate patient interactions and acquisition of medical data, increased potential for missing significant clinical findings, decreased quality of care, and potential medical liability. CONCLUSION: Oncology/hematology patients and their physicians expressed high levels of satisfaction with the use of telehealth video visits. Despite recent advances in technology, there are still opportunities to improve the equal implementation of telemedicine for the medical care of vulnerable older, low-income, and underinsured patient populations.

The Liver That Cured Christmas: Case Report of Orthotopic Liver Transplant in a Patient with Hemophilia B.

Herein, we discuss a case of a 39-year-old male with hemophilia B, who developed end-stage liver disease secondary to nonalcoholic steatohepatitis, that underwent orthotopic liver transplantation (OLT) as a curative means for his liver disease and coagulation disorder. Existing case reports have demonstrated favorable outcomes in patients outside of the United States who received continuous infusions of recombinant factor IX replacement in the perioperative setting after liver transplant. Given limitations in the stability of the recombinant factor IX products in the United States, a dosing strategy was comprised of once daily bolus dosing to achieve satisfactory factor IX levels. Within 48 hours of initial surgery, the patient had sustained factor IX levels above 70% of normal and the patient required no further dosing of factor IX products to date. This strategy helped facilitate less frequent dosing as well as achieved targeted factor levels while synthetic function of the transplanted liver recovered.

Viable Hemostasis Obtained With Prothrombin Complex Concentrate in Patients Who Refuse Standard Allogeneic Blood Transfusion and Undergo Complex Cardiac Surgery: A Case Series.

Human 4-factor prothrombin complex concentrate (4F-PCC) may reduce blood loss during surgery. This case series described perioperative outcomes among 9 patients who refused standard allogeneic blood transfusion, underwent complex cardiac surgery with aortic involvement, and received intraoperative 4F-PCC. Additional intraoperative cointerventions included protamine (n = 9), aminocaproic acid (n = 8), fibrinogen concentrate (n = 6), desmopressin (n = 6), factor VIIa (n = 2), and tranexamic acid (n = 1). Outcomes included postoperative death (n = 1), major postoperative bleeding (n = 1), deep vein thrombosis (n = 2), and ischemic stroke (n = 1). When standard allogeneic blood transfusion is refused, viable hemostasis can be obtained using 4F-PCC during complex cardiac surgeries with a high risk of bleeding.

Is Surgery-first Still a Reasonable Option in the Era of Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer?

The incidence of pancreatic ductal adenocarcinoma has risen rapidly. By 2030, it is likely to be the second most prevalent cause of death by cancer, following cancer of the lung. Unfortunately, most patients present with advanced disease. In fact, only 20% of patients are candidates for surgery. More research is needed to find dependable treatment options for this disease. Although we wait for more effective treatments to be developed, we continue using chemotherapy, radiation, and surgery-all with less than optimal outcomes. There is a debate about using chemotherapy in the neoadjuvant setting and counter-debate about better outcomes in the adjuvant settings. In the neoadjuvant setting, not everyone is able to make it to surgery; conversely, in the adjuvant setting, not everyone is able to make it to chemotherapy. Drop-out data after surgery are widely available, but similar drop-out rates after neoadjuvant treatment are not widely published. Here, we will analyze the literature to better understand the treatment strategies and outcomes of pancreatic ductal adenocarcinoma. We argue in favor of an upfront surgery and adjuvant therapy strategy for better outcomes and patient quality of life.

Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria. METHODS: Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary. RESULTS: Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053). CONCLUSIONS: Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.

Aortic Valve Replacement in Severe Factor V Deficiency and Inhibitor: Diagnostic and Management Challenges.

Factor V (FV) deficiency (F5D) is a rare hematological disorder with a variable spectrum of bleeding manifestations. Until now, no specific protocols for the management of these patients have been established. However, available literature suggests that perioperative infusion of fresh frozen plasma (FFP) may help maintain FV levels to prevent bleeding. We present the case of a 64-year-old man with previously undiagnosed severe FV deficiency and mild FV inhibitor, who underwent aortic valve replacement with no bleeding complications.

Promising new treatments for pancreatic cancer in the era of targeted and immune therapies.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality among men and women in the United States. Its incidence has been on the rise, with a projected two-fold increase by 2030. PDAC carries a poor prognosis due to a lack of effective screening tools, limited understanding of pathophysiology, and ineffective treatment modalities. Recently, there has been a revolution in the world of oncology with the advent of novel treatments to combat this disease. However, the 5-year survival of PDAC remains unchanged at a dismal 8%. The aim of this review is to bring together several studies and identify various recent modalities that have been promising in treating PDAC.

Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series.

BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS: In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS: Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION: Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING: None.