Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients with Unresectable HCC.

BACKGROUND & AIMS: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC. METHODS: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients. RESULTS: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients. CONCLUSIONS: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays.

Viral esophagitis in non-human immunodeficiency virus patients: a case-control study.

Background: Esophagitis, inflammation of the esophagus, can result from various causes, including reflux, infections, food allergies, medications, and trauma. Infectious esophagitis is the third most common cause after gastroesophageal reflux disease (GERD) and eosinophilic esophagitis worldwide. The primary causes of infectious esophagitis are candida esophagitis and viral esophagitis (VE) caused by herpes simplex virus (HSV) or cytomegalovirus (CMV). VE is typically associated with immunosuppression, with risk factors such as malignancy, chemotherapy, organ transplant, and human immunodeficiency virus (HIV). Infectious esophagitis is prevalent in about one-third of untreated acquired immunodeficiency syndrome (AIDS) patients, but recent reports indicate an increase in VE cases among immunocompetent individuals. This study aims to explore risk factors and patient demographics in non-HIV individuals. Methods: A case-control study that included patients 18 years and older diagnosed with HSV or CMV esophagitis who were identified through histopathologic examination or immunohistochemical staining. Cases were obtained by searching pathology reports between 2009-2022 from five MedStar Health Hospitals in the District of Columbia and Maryland. Controls were selected based on International Classification of Diseases (ICD) codes for esophagogastroduodenoscopy (EGD) with negative VE results within the same period. Patient demographics, comorbidities, laboratory parameters, endoscopic findings, and potential risk factors were collected through chart review. Results: Out of 40,224 cases between 2009-2022, 50 cases of VE were identified, with 30 cases attributed to HSV, 19 cases to CMV, and one case of HSV/CMV coinfection. Hematemesis was the predominant symptom in patients with HSV (33%), while dysphagia was more prevalent in CMV patients (42%). The most common finding during EGD was ulceration in HSV patients (67%) and esophagitis in CMV patients (37%). Patients with VE had a higher likelihood of a history of immunosuppressive therapy, organ transplant, active malignancy, and systemic steroid use. However, a significant portion (34%) had no identifiable risk factors. Conclusions: The study's findings contribute to a better understanding of the clinical characteristics and risk factors associated with VE in non-HIV patients. The identification of immunosuppression and specific risk factors can aid in early detection, appropriate management, and targeted interventions for VE. Further research is warranted to explore the rising incidence of VE in immunocompetent individuals and to optimize preventive strategies and treatment approaches for this condition.

Atypical RhoUV GTPases in development and disease.

RhoU and RhoV are members of the Rho family of small GTPases that comprise their own subfamily. RhoUV GTPases are classified as atypical due to the kinetics of their GTP/GDP binding cycles. They also possess unique N- and C-termini that regulate their subcellular localization and activity. RhoU and RhoV have been linked to cytoskeletal regulation, cell adhesion, and cell migration. They each exhibit distinct expression patterns during embryonic development and diseases such as cancer metastasis, suggesting they have specialized functions. In this review, we will discuss the known functions of RhoU and RhoV, with a focus on their roles in early development, organogenesis, and disease.

Clinical outcomes: endoscopic resection of duodenal ampullary lesions.

Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews. The objective of this study is to describe endoscopic papillectomy outcomes to further refine management guidelines. Methods: This is a retrospective study of patients who underwent endoscopic papillectomy. Demographic data were included. Details regarding lesions and procedures were also collected, including endoscopic impression, size, resection method and adjunctive therapies. Chi-square, Kruskal-Wallis rank-sum, and t-tests were performed. Results: A total of 90 patients were included. 60% patients (54 of 90) had pathology-proven adenomas. 14.4% of all lesions (13 of 90) and 18.5% of adenomas (10 of 54) were treated with APC. Among APC-treated lesions, 36.4% developed recurrence (4 of 11) vs. 7.1% developed residual lesion (1 of 14) (P=0.019). 15.6% of all lesions (14 of 90) and 18.5% of adenomas (10 of 54) reported complications, and the most common was pancreatitis (11.1% and 5.6%). Median follow-up time was 8 months for all lesions and 14 months (range, 1-177 months) for adenomas, with time to recurrence 30 and 31 months (range, 1-137 months), respectively. Recurrence was observed in 16.7% of all lesions (15 of 90) and 20.4% of adenomas (11 of 54). Endoscopic success was observed in 69.2% of all lesions (54 of 78) and 71.4% of adenomas (35 of 49) after removing patients lost to follow-up. Conclusions: Endoscopic papillectomy is an effective method for managing duodenal adenomas. Pathology-proven adenoma should undergo surveillance for at least 31 months. Lesions treated with APC may require closer follow-up and for a prolonged period.

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Real-world incidence of venetoclax toxicities in British Columbia.

INTRODUCTION: Venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (r/r CLL). Tumour lysis syndrome (TLS) is a serious toxicity associated with venetoclax, and real-world studies suggest that the incidence may be higher than in clinical trials. The purpose of this study is to describe the incidence of venetoclax toxicities in British Columbia (BC). METHODS: Retrospective review of electronic medical charts for patient characteristics and clinical outcomes of patients treated with venetoclax for r/r CLL in BC. Patients were classified according to their risk for developing TLS. The incidence of TLS was categorized based on laboratory metrics or clinical diagnosis. Other non-TLS toxicities were also collected. RESULTS: Of 33 patients identified, 40%, 33%, and 27% were at low, intermediate, and high risk for TLS, respectively. Laboratory TLS occurred in 1/33 patients (3%), and no clinical TLS was reported. Grade 3 or 4 toxicities occurred in 19/33 patients (58%). Of these, neutropenia was the most common, occurring in 16 patients (84%) followed by thrombocytopenia, which occurred in 8 patients (42%). CONCLUSIONS: The incidence of TLS in patients treated with venetoclax for r/r CLL in BC was lower than in other real-world studies. Findings may warrant further investigation to determine if the higher incidence of TLS in real-world reports may be mitigated through modifying TLS risk categorization and associated prophylactic measures. Neutropenia was the most common grade 3 or 4 venetoclax toxicity reported, and the incidence in BC is comparable to other centres.

Risk Factors for Misuse of Prescribed Opioids: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVE: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective is to synthesize the available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing misuse among patients prescribed opioids for noncancer pain. METHODS: We performed a systematic search of the scientific and gray literature for studies reporting on risk factors for prescription opioid misuse. Two reviewers independently reviewed titles, abstracts, and full texts; extracted data; and assessed study quality. We excluded studies with greater than 50% cancer patients, palliative patients, and illicit opioid initiation. When possible, we synthesized the effect sizes of dichotomous risk factors and their associations with opioid misuse, using inverse-variance random-effects meta-analysis. We calculated the mean difference between opioid misusers and nonmisusers for continuous risk factors. When studies lacked homogeneity, we synthesized their results qualitatively. RESULTS: Of 9,629 studies, 65 met our inclusion criteria. Among patients with outpatient opioid prescriptions, the following factors were associated with the development of misuse: any current or previous substance use (odds ratio [OR] 3.55; 95% confidence interval [CI] 2.62 to 4.82), any mental health diagnosis (OR 2.45; 95% CI 1.91 to 3.15), younger age (OR 2.19; 95% CI 1.81 to 2.64), and male sex (OR 1.23; 95% CI 1.10 to 1.36). CONCLUSION: Although clinicians should endeavor to offer alternative pain management strategies to all patients, those who are younger, are male patients, and report a history of or current substance use or mental health diagnoses were associated with a greater risk of developing opioid misuse. Clinicians should consider prioritizing alternative pain management strategies for these higher-risk patients.

Clinical Evaluation of Large Diameter Rigid-Gas Permeable Versus Soft Toric Contact Lenses for the Correction of Refractive Astigmatism. A MultiCenter Study.

PURPOSE: This study aims to address the clinical performance of a large diameter rigid gas permeable lens (LRGP) in a group of subjects with low-to-moderate (0.75-2.75 D) refractive astigmatism. An additional goal was to determine whether soft toric or LRGP contact lenses performed better objectively in the correction of astigmatism and to determine which modality is preferred by subjects. METHODS: This was a multisite prospective cross-over clinical study. Ten asymptomatic contact lens wearers per site (four university clinics) were recruited and randomly assigned to group A or group B. Group A was assigned to start wearing Comfilcon A soft toric lens first, for two weeks, and then crossed over to LRGP lenses (Boston XO, 14.3 mm diameter miniscleral lens). Group B initially wore LRGP lenses and then crossed over to soft toric lenses. For each type of lens worn, low-contrast and high-contrast visual acuity (VA) were evaluated at distance. At the conclusion of the study, after two months, all subjects completed a questionnaire in which they were asked to indicate their preference for one type of lens (soft toric or LRGP) and to rate the quality of vision in day-to-day activities. RESULTS: Thirty-six of 38 (94.7%) subjects completed the study with 75% preferring the vision of the LRGP lens as compared to the soft toric lenses worn in the study. 52.7% expressed a preference to continue with this modality despite only 38.8% reporting that these LRGP lenses are easy or very easy to handle. Wear time, subjective comfort, and subjective vision ratings exhibited no significant difference between the two groups. CONCLUSIONS: In a population of asymptomatic contact lens wearers, LRGP lenses can be considered as a good alternative to soft toric lenses for the correction of refractive astigmatism.

Risk factors for addiction among patients receiving prescribed opioids: a systematic review protocol.

BACKGROUND: Opioid addiction prevention has become an urgent public health priority, with several countries declaring a state of emergency due to rising death tolls from opioid abuse. Reducing the risk of developing addiction among opioid-naïve patients exposed to prescribed opioids during the process of medical care may be an important primary prevention strategy. Our objective is to synthesize the available evidence about factors associated with the development of addiction among patients first exposed to prescribed opioids, with a focus on opioid-naïve patients. METHODS: We will perform a systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and other databases in collaboration with a health information specialist using a comprehensive search strategy. We will also supplement our search with a scan of the grey literature to identify relevant ongoing and unpublished studies. We will include studies reporting on risk factors for opioid addiction in patients prescribed opioid analgesic therapy through a prescription from a licensed medical professional, with a focus on opioid-naïve patients. We will exclude studies focusing on patients who are first exposed to illicit opioids, those who use prescription opioids for cancer pain, and/or who are palliative. Two reviewers will independently review titles, abstracts, and full texts for inclusion and exclusion criteria. They will then extract data from included full texts using standardized piloted data extraction forms and assess study quality through risk of bias assessment. We will synthesize the effect sizes of risk factors derived from clinically homogenous studies with similar designs and the remaining ones qualitatively. DISCUSSION: Understanding risk factors for opioid addiction among patients who require analgesia has the potential to inform clinical care and opioid prescribing guidelines aiming to reduce opioid addiction. We will also use this information as a starting point for developing interventions for primary prevention.

Long-term outcomes of stereotactic body radiation therapy (SBRT) with fiducial tracking for inoperable stage I non-small cell lung cancer (NSCLC).

BACKGROUND: Stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) is considered standard of care in the medically inoperable patient population. Multiple methods of SBRT delivery exist including fiducial-based tumor tracking, which allows for smaller treatment margins and avoidance of patient immobilization devices. We explore the long-term clinical outcomes of this novel fiducial-based SBRT method. METHODS: In this single institutional retrospective review, we detail the outcomes of medically inoperable pathologically confirmed stage I NSCLC. Patients were treated with the Cyberknife SBRT system using a planning target volume (PTV) defined as a 5-mm expansion from gross tumor volume (GTV) without creation of an internal target volume (ITV). Dose was delivered in three or five equal fractions of 10 to 20 Gy. Pretreatment and posttreatment pulmonary function test (PFT) changes and evidence of late radiological rib fractures were analyzed for the majority of patients. Actuarial local control, locoregional control, distant control, and overall survival were calculated using the Kaplan-Meier method. RESULTS: Sixty-one patients with a median age of 75 years were available for analysis. The majority (80 %) of patients were deemed to be medically inoperable due to underlying pulmonary dysfunction. Eleven patients (18 %) developed symptomatic pneumothoraces secondary to fiducial placement under CT guidance, which precipitously dropped to 0 % following transition to bronchoscopic fiducial placement. The 2-year rib fracture risk was 21.4 % with a median time to rib fracture of 2.9 years. PFTs averaged over all patients and parameters demonstrated small absolute declines, 5.7 % averaged PFT decline, at approximately 1 year of follow-up, but only the diffusing capacity of lung for carbon monoxide (DLCO) demonstrated a statistically significant decline (10.29 vs. 9.01 mL/min/mmHg, p = 0.01). Five-year local control, locoregional control, and overall survival were 87.6, 71.8, and 39.3 %, respectively. CONCLUSIONS: Despite reduced treatment margins and lack of patient immobilization, SBRT with fiducial-based tumor tracking achieves clinically comparable long-term outcomes to other linac-based SBRT approaches.

Cross-cultural verification of the EORTC QLQ-C15-PAL questionnaire in mainland China.

BACKGROUND: Simplified by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30), EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) is specifically applied to evaluating palliative care patients' quality of life. AIM: This study examined cross-cultural adaptability and validity of QLQ-C15-PAL for evaluating quality of life of palliative care patients with advanced cancer in mainland China. PARTICIPANTS AND DESIGN: From May to October 2013, 243 palliative care patients in Tianjin Cancer Hospital completed the EORTC QLQ-C30. We extracted QLQ-C15-PAL data for analysis. Physicians completed the Eastern Cooperative Oncology Group Performance Status score and mental state assessment for each patient. RESULTS: A total of 243 patients completed the study. The compliance rate was high, with missing rate for each item ranging from 0% to 2.1%. In addition to emotional function, the remaining dimensions demonstrated a high reliability (Cronbach's alpha > 0.7). Whether we divided patients into two groups according to their Eastern Cooperative Oncology Group Performance Status or divided patients into three groups according to mental status, both sets of results showed significant differences in QLQ-C15-PAL subscale scores (p < 0.05), indicating that the QLQ-C15-PAL scale could be used to distinguish between the aforementioned subgroups. Overall quality of life was moderately correlated with fatigue (r = -0.406) but weakly correlated with other subscales. The proportion of variance (R(2)) ranged from 0.848 to 0.903, which showed that QLQ-C15-PAL subscale scores explained between 84.8% and 90.3% of the original QLQ-C30 score distribution. CONCLUSION: The Chinese version of the EORTC QLQ-C15-PAL questionnaire has high reliability and validity and is therefore suitable for clinical use in China to determine health-related quality of life in Chinese patients with advanced cancer.

Validation of EORTC IN-PATSAT32 for Chinese cancer patients.

PURPOSE: The aim of this study is to test the psychometric properties and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) inpatient satisfaction with care questionnaire 32 (IN-PATSAT32) for evaluating Chinese cancer patients and to analyze the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction. METHODS: Three hundred two cancer inpatients in Tianjin Cancer Institution and Hospital from June 2013 to December 2013 were recruited for this study. All participants self-administered the EORTC IN-PATSAT32 and EORTC quality of life questionnaire-core 30 (QLQ-C30). Psychometric evaluation of the validity, reliability, acceptability, as well as the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction, was conducted. RESULTS: A favorable internal consistency reliability was confirmed, as the Cronbach's α coefficients were >0.80 for all scales in the EORTC IN-PATSAT32, ranging from 0.849 to 0.944. Multi-trait scaling analysis showed that all item-scale correlation coefficients met the standard of convergent validity, and 79.3 % met the standard of discriminant validity. Weak correlations were found between the scales and single items of the EORTC IN-PATSAT32 and EORTC QLQ-C30, proving the validity of EORTC IN-PATSAT32. None of the EORTC IN-PATSAT32 scales were able to discriminate between patients across age categories, while significant influences of educational level on doctors' and nurses' conduct, as well as influences of diagnostic time and tumor stage on nurses' conduct, and information provision scales were discovered. The questionnaire was easily understood with a satisfactory acceptability. CONCLUSIONS: The EORTC IN-PATSAT32 appears to be a reliable, valid, and acceptable instrument to use on cancer patients and is appropriate for measuring the patient satisfaction of Chinese patients.

Validation of EORTC QLQ-LC43 for Chinese patients with lung cancer.

OBJECTIVES: To test the validity, reliability and acceptability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 43 (EORTC QLQ-LC43) for Chinese patients with lung cancer. MATERIALS AND METHODS: Patients from Tianjin Cancer Institution and Hospital with lung cancer were enrolled in this study. All were treated in Tianjin Cancer Institution and Hospital from December 2012 to April 2013. All participants self-administered the EORTC QLQ-LC43 and the Short Form 36 Health Survey (SF-36). The Karnofsky performance scale (KPS) was performed to evaluate scores. Reliability test of the questionnaires was based on Cronbach's α coefficients, Pearson correlation test and Kruskal-Wallis test. RESULTS: This study included 317 inpatients and outpatients. The Cronbach's α coefficients were >0.70 in all scales of the two questionnaires, except that of cognitive functioning. High correlations were found among the quality of life (QoL), physical functioning, role functioning, dyspnea, and KPS scores (r>0.40). Mild correlations were discovered among the rest of the items. Dividing the participants into three groups based on the KPS scores showed that QoL and functional scales scores progressively decreased and the symptom items scores progressively increased as KPS scores decreased. All inter-group differences were statistically significant (P<0.05). CONCLUSION: The EORTC QLQ-LC43 is a reliable and valid instrument in patients with lung cancer and is appropriate for measuring the QoL of Chinese patients.

Investigation and analysis of oncologists' knowledge of morphine usage in cancer pain treatment.

PURPOSE: To examine oncologists' knowledge of cancer pain and morphine's clinical application in the People's Republic of China. In addition, this study analyzes and discusses the negative factors that currently affect the clinical application of morphine. PATIENTS AND METHODS: A questionnaire survey was given to a random sample of 150 oncologists from Tianjin Medical University Cancer Institute and Hospital. The statistical results were analyzed and processed using SPSS version 21.0 and Matlab version 2012a statistical software. Single-factor analysis of variance, Kruskal-Wallis nonparametric test, and independent samples t-test were adopted to analyze the difference in knowledge scores of morphine usage. The study also identified major impediment factors on clinical use of morphine. RESULTS: Among the 127 respondents, morphine controlled-release tablets were the most popular drug chosen to treat severe cancer pain (76 respondents, 35.8%). Participants who reported having received training in cancer pain management and drug use demonstrated a significantly higher mean score of basic knowledge compared with their untrained peers (11.51±2.60 versus 9.28±3.68, t=2.48, P=0.022). The top four barriers to widespread clinical use of morphine for cancer pain were 1) insufficient analgesia administration training for medical personnel, 2) poor patient compliance, 3) drug side effects, and 4) concerns surrounding drug addiction. CONCLUSION: The oncologists in the People's Republic of China simultaneously lack comprehensive knowledge and harbor misconceptions with regard to cancer pain treatment and morphine's clinical application. Creating professional training initiatives for oncologists is necessary to enhance their awareness and expertise in morphine use for cancer pain treatment.