Impact of DAA Treatment for HCV on Hepatocellular Carcinoma in a Predominately African American Population.

PURPOSE: This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment. METHODS: All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022. RESULTS: There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis. CONCLUSIONS: Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes. WHAT IS KNOWN: • African Americans are more likely to have HCV infection as compared to non-AA. • Hepatocellular carcinoma is increasing in incidence in the US. • The role of HCV in the development of HCC remains to be further investigated. WHAT IS NEW: • HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. • HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. • African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).

Gastric Cancer Survivorship: Multidisciplinary Management, Best Practices and Opportunities.

PURPOSE: Gastric cancer is the 5th most common malignancy worldwide. As early detection increases and treatments for gastric cancer improve, the number of gastric cancer survivors grows. METHODS: Here, we review the diagnosis and management of gastric cancer and discuss important considerations for gastric cancer survivorship including cancer surveillance, weight loss, malnutrition, fatigue, specific complications related to surgery and radiation, quality of life in gastric cancer survivorship, health behavior, and models of survivorship. RESULTS: Multimodality therapy with chemotherapy and surgery can result in chronic toxicities in multiple organ systems. This emphasizes the need for a multidisciplinary survivorship care model including cancer surveillance, management of chronic toxicities, and optimization of modifiable risk factors with long-term involvement of appropriate providers. CONCLUSION: Adequately caring for gastric cancer survivors requires a coordinated, multidisciplinary approach.

Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management.

Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.

Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies.

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.

Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.

KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we evaluated the combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We found that cancer cells resistant to KRASG12C inhibitor were sensitive to KPT9274-induced growth inhibition. Furthermore, KPT9274 synergized with sotorasib and adagrasib to inhibit the growth of KRASG12C-mutant cancer cells and reduce their clonogenic potential. Mechanistically, this combination suppressed cell growth signaling and downregulated cell-cycle markers. In a PDAC cell line-derived xenograft (CDX) model, the combination of a suboptimal dose of KPT9274 with sotorasib significantly reduced the tumor burden (P= 0.002). Similarly, potent antitumor efficacy was observed in an NSCLC CDX model, in which KPT9274, given as maintenance therapy, prevented tumor relapse following the discontinuation of sotorasib treatment (P= 0.0001). Moreover, the combination of KPT9274 and sotorasib enhances survival. In conclusion, this is the first study to demonstrate that KRASG12C inhibitors can synergize with the PAK4 inhibitor KPT9274 and combining KRASG12C inhibitors with KPT9274 can lead to remarkably enhanced antitumor activity and survival benefits, providing a novel combination therapy for patients with cancer who do not respond or develop resistance to KRASG12C inhibitor treatment.

Interventions to Improve Surveillance for Hepatocellular Carcinoma in High-Risk Patients: A Scoping Review.

PURPOSE: Hepatocellular carcinoma (HCC) is most often a sequela of chronic liver disease or chronic hepatitis B infection. Among high-risk patients, surveillance for HCC every 6 months is recommended by international guidelines. However, rates of HCC surveillance are suboptimal (11-64%). Barriers at the patient, provider, and healthcare delivery system levels have been identified. METHODS: We performed a systemic scoping review to identify and characterize interventions to improve HCC surveillance that has previously been evaluated. Searches using key terms in PubMed and Embase were performed to identify studies examining interventions designed to improve the surveillance rate for HCC in patients with cirrhosis or chronic liver disease that were published in English between January 1990 and September 2021. RESULTS: Included studies (14) had the following study designs: (1) randomized clinical trials (3, 21.4%), (2) quasi-experimental (2, 14.3%), (3) prospective cohort (6, 42.8%), and (4) retrospective cohort (3, 21.4%). Interventions included mailed outreach invitations, nursing outreach, patient education with or without printed materials, provider education, patient navigation, chronic disease management programs, nursing-led protocols for image ordering, automated reminders to physicians and nurses, web-based clinical management tools, HCC surveillance databases, provider compliance reports, radiology-led surveillance programs, subsidized HCC surveillance, and the use of oral medications. It was found that HCC surveillance rates increased after intervention implementation in all studies. CONCLUSION: Despite improvements in HCC surveillance rates with intervention, compliance remained suboptimal. Further analysis of which interventions yield the greatest increases in HCC surveillance, design of multi-pronged strategies, and improved implementation are needed.

Locoregional Therapy for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable liver-only or liver-dominant ICC. This review explores the role of these therapies in the treatment of ICC, including radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), external beam radiotherapy (EBRT), stereotactic body radiotherapy (SBRT), hepatic arterial infusion (HAI) of chemotherapy, irreversible electroporation (IE), and brachytherapy. A search of the current literature was performed to examine types of LRT currently used in the treatment of ICC. We examined patient selection, technique, and outcomes of each type. Overall, LRTs are well-tolerated in the treatment of ICC and are effective in improving overall survival (OS) in this patient population. Further studies are needed to reduce bias from heterogenous patient populations and small sample sizes, as well as to determine whether certain LRTs are superior to others and to examine optimal treatment selection.

Provider-To-Provider Communication About Care Transitions: Considering Different Health Technology Tools.

ABSTRACT: Transitions in patient care require exchanges of information between providers. This period of transition presents a range of challenges, and inadequate transitions can have serious consequences for patients. Our objective was to understand providers' perspectives about patient care transitions, especially around communication between providers and the role of health information technology in provider-to-provider communication. Semi-structured interviews were conducted. Deductive-dominant thematic analysis was used to allow categorization of data based on general themes derived from the interview guides, as well as identification of emergent themes. We characterized three main themes involving providers' perspectives about care transitions. Themes included communication challenges, communication preferences, and suggestions for improving the care transition processes. With respect to challenges around communication, providers highlighted four main concerns. These concerns included the existence of too many methods of communication, high volume of communication, challenges with involvement of multiple providers delivering longitudinal care, and difficulty communicating with providers outside the health system. Providers noted opportunities to improve transitions including improving standardization, enhancing the specialty to primary care transition process, and increasing communication back to the referring provider. Implementation and evaluation of these improvements could be considered by health systems to enhance care transitions.

Congenital Absence of the Portal Vein.

A 59-year-old woman presented with abdominal bloating, elevated alkaline phosphatase and transaminases, and computed tomography abdomen/pelvis demonstrating large right-sided hepatic masses. A percutaneous fine needle aspiration demonstrated hepatocellular neoplasm concerning for hepatocellular carcinoma. Preoperative imaging demonstrated possible porto-caval shunt. She underwent uneventful right hepatic lobectomy with confirmation of porto-systemic shunt. Congenital porto-systemic shunt, or Abernethy malformation, is rare and is associated with congenital cardiac and gastrointestinal abnormalities. Additionally, congenital porto-systemic shunt is associated with increased risk of hepatic neoplasms including hepatocellular carcinoma. Recommended surveillance for these patients is not well defined.

Patient-, Provider-, and System-Level Barriers to Surveillance for Hepatocellular Carcinoma in High-Risk Patients in the USA: a Scoping Review.

PURPOSE: Hepatocellular carcinoma has a dismal prognosis, except in patients diagnosed early who are candidates for potentially curative therapies. Most HCC cases develop in patients with chronic liver disease. Therefore, expert society guidelines recommend surveillance every 6 months with ultrasound with or without serum alpha-fetoprotein for high-risk patients. However, fewer than 20% of patients in the USA undergo appropriate surveillance. METHODS: A systematic scoping review was performed with the objective of identifying barriers to screening among high-risk patients in the USA including mapping key concepts in the relevant literature, identifying the main sources and types of evidence available, and identifying gaps in the literature. A total of 43 studies published from 2007 to 2021 were included. Data were extracted and a conceptual framework was created. RESULTS: Assessment of quantitative studies revealed poor surveillance rates, often below 50%. Three categories of barriers to surveillance were identified: patient-level, provider-level, and system-level barriers. Prevalent patient-level barriers included financial constraints, lack of awareness of surveillance recommendations, and scheduling difficulties. Common provider-level barriers were lack of provider awareness of guidelines for surveillance, difficulty accessing specialty resources, and time constraints in the clinic. System-level barriers included fewer clinic visits and rural/safety-net settings. Proposed interventions include improved patient/provider education, patient navigators, increased community/academic collaboration, and EMR-based reminders. CONCLUSION: Based on these findings, there is a crucial need to implement and evaluate proposed interventions to improve HCC surveillance.

Concerns and frustrations about the public reporting of device-related healthcare-associated infections: Perspectives of hospital leaders and staff.

BACKGROUND: Public reporting of healthcare-associated infections (HAIs) aims to incentivize improvement in infection prevention. The motivation and mechanisms of public reporting have raised concerns about the reliability of this data, but little is known about the specific concerns of hospital leaders and staff. This study sought to better understand perspectives of individuals in these roles regarding the identification and public reporting of HAIs. METHODS: We conducted interviews with 471 participants including hospitals leaders (eg, administrative and clinical leaders) and hospital staff (eg, physicians and nurses) between 2017 and 2019 across 18 US hospitals. A semistructured interview guide was used to explore perspectives about the use of HAI data within the context of management strategies used to support infection prevention. RESULTS: Interviewees described concerns about public reporting of HAI data, including a lack of trust in the data and inadvertent consequences of its public reporting, as well as specific frustrations related to the identification and accountability for publicly-reported HAIs. CONCLUSION: Concerns and frustrations related to public reporting of HAI data highlight the need for improved guidelines, transparency, and incentives. Efforts to build trust in publicly-reported HAI data can help ensure this information is used effectively to improve infection prevention practices.

Conditional Survival Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. PATIENTS AND METHODS: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. RESULTS: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. CONCLUSION: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.

Surgical Treatment of Distal Cholangiocarcinoma.

Distal cholangiocarcinoma (dCCA) is a rare malignancy arising from the epithelial cells of the distal biliary tract and has a poor prognosis. dCCA is often clinically silent and patients commonly present with locally advanced and/or distant disease. For patients identified with early stage, resectable disease, surgical resection with negative margins remains the only curative treatment strategy available. However, despite appropriate treatment and diligent surveillance, risk of recurrence remains high with nearly 50% of patients experiencing recurrence at 5 years subsequent to surgical resection; therefore, it is prudent to continue to optimize neoadjuvant and adjuvant therapies in order to reduce the risk of recurrence and improve overall survival. In this review, we discuss the clinical presentation, workup and surgical treatment of dCCA.

Using machine learning to preoperatively stratify prognosis among patients with gallbladder cancer: a multi-institutional analysis.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy associated with a high risk of recurrence and mortality. We used a machine-based learning approach to stratify patients into distinct prognostic groups using preperative variables. METHODS: Patients undergoing curative-intent resection of GBC were identified using a multi-institutional database. A classification and regression tree (CART) was used to stratify patients relative to overall survival (OS) based on preoperative clinical factors. RESULTS: CART analysis identified tumor size, biliary drainage, carbohydrate antigen 19-9 (CA19-9) levels, and neutrophil-lymphocyte ratio (NLR) as the factors most strongly associated with OS. Machine learning cohorted patients into four prognostic groups: Group 1 (n = 109): NLR ≤1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 2 (n = 88): NLR >1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 3 (n = 46): CA19-9 >20, no drainage, tumor size <5.0 cm; Group 4 (n = 77): tumor size <5.0 cm with drainage OR tumor size ≥5.0 cm. Median OS decreased incrementally with CART group designation (59.5, 27.6, 20.6, and 12.1 months; p < 0.0001). CONCLUSIONS: A machine-based model was able to stratify GBC patients into four distinct prognostic groups based only on preoperative characteristics. Characterizing patient prognosis with machine learning tools may help physicians provide more patient-centered care.

Burnout Assessment Among Surgeons and Surgical Trainees During the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: The objective of the current study was to summarize current research on burnout among surgical trainees and surgeons during the COVID-19 pandemic. METHODS: PubMed, SCOPUS, Embase, and Psych INFO were systematically searched for studies that evaluated burnout during the COVID-19 pandemic among surgical trainees and surgeons. RESULTS: A total of 29 articles met inclusion criteria, most of which originated from the United States (n = 18, 62.1%). Rates of burnout ranged from 6.0% to 86.0%. Personal factors responsible for burnout were fear of contracting/transmitting COVID-19 (8 studies, 27.6%), female gender (8, 27.6%), and younger age (5, 17.2%). Professional factors contributing to burnout included increased COVID-19 patient clinical load (6, 20.7%), limited work experience (6, 20.7%), reduction in operative cases (5, 17.2%) and redeployment to COVID-19 wards (4, 13.8%). The COVID-19 pandemic negatively impacted surgical education due to reduced number of operative cases (11, 37.9%), decreased hands-on experience (4, 13.8%), and not being able to complete case requirements (3, 10.34%). The shift of didactics to virtual formats (3, 10.3%), increased use of telemedicine (2, 6.9%), and improved camaraderie among residents (1, 3.4%) were viewed as positive consequences. CONCLUSION: COVID-19 related burnout was reported in as many as 1 in 2 surgical trainees and attending surgeons. Intrinsic- (i.e., gender, age), family- (i.e., family/being married/having children or being single/not having children), as well as work-related extrinsic- (i.e., work-force deployment, risk of infection/spread, changes in educational format) factors were strongly associated with risk of burnout. These factors should be considered when designing interventions to ameliorate burnout among surgical trainees and surgeons.

Comparing Minimally Invasive and Open Pancreaticoduodenectomy for the Treatment of Pancreatic Cancer: a Win Ratio Analysis.

INTRODUCTION: Despite its rising adoption, the use of minimally invasive (MIS) pancreaticoduodenectomy (PD) in the treatment of pancreatic cancer remains controversial. We sought to compare MIS and open PD for pancreatic cancer resection in terms of short-term, long-term, and oncologic outcomes using the win ratio, a novel statistical approach. METHODS: Patients undergoing PD for pancreatic adenocarcinoma 2010-2016 were identified from the National Cancer Database (NCDB). Patients were paired based on age, sex, race, tumor size, Charlson-Deyo score, and receipt of neoadjuvant chemotherapy. The win ratio was calculated based on 30-day and 3-year mortality, receipt of adjuvant chemotherapy, surgical margin status, examination of at least 11 lymph nodes, extended length of stay, and 30-day readmission. RESULTS: Among 18,936 patients, median age was 67 (IQR: 60-74); most patients had stage II disease at diagnosis (n = 16,530, 87.3%) and tumor size ≥ 2 cm (n = 15,880, 83.9%). The majority of patients underwent open PD (n = 16,409, 86.7%) versus MIS PD (n = 2527, 13.3%). For every matched patient-patient pair, the odds of the patient undergoing MIS PD "winning" were 1.14 (95%CI 1.13-1.15) higher versus open PD. The benefits of MIS PD were most pronounced among patients with tumor size < 2 cm (WR 1.21, 95%CI 1.13-1.30 versus ≥ 2 cm, WR 1.13, 95%CI 1.12-1.14) and patients who received neoadjuvant chemotherapy prior to resection (WR 1.28, 95%CI 1.23-1.32 versus no neoadjuvant chemotherapy, WR 1.13, 95%CI 1.11-1.14). CONCLUSIONS: MIS PD may be preferable to open PD based on a hierarchical composite outcome that considered short-term, long-term, and oncologic outcomes.