Hepatocellular Carcinoma Presenting as a Clival Mass

Introduction: Hepatocellular carcinoma (HCC) comprises the majority of primary liver cancer and has a poor prognosis. Clivus metastasis is rare with only a few reported cases in the medical literature. We report a case of a patient who presented with clival mass found to have metastatic HCC. Case Description/Methods: A 63-year-old woman presented for neurosurgical evaluation after she was found to have a skull base mass on computerized tomography (CT) of the head at an outside hospital. She endorsed dysphagia for three months, however denied headaches or visual disturbances. A magnetic resonance imaging (MRI) revealed a 5.4 cm by 2.9 cm by 3.6 cm mass in the clivus, which was deemed as the cause of dysphagia (Figure 1a). The patient subsequently underwent an endoscopic transsphenoidal resection of the clival mass. Histopathology from the tissue revealed a hepatoid carcinoma, concerning for metastatic HCC (Figure 1b and 2c). Immunohistochemical strains were positive for hepatocytic marker arginase-1 (Figure 1d). Laboratory studies revealed alpha fetoprotein (AFP) of 56,344 ng/mL, CA-125 of 376 ng/mL, normal B-HCG and carcinoembryonic antigen (CEA). Thereafter, a triple phase CT of the liver revealed two LI-RADS 5 lesions suggestive of HCC as the primary malignancy. Patient's case was discussed at multidisciplinary tumor board with recommendations for systemic immunotherapy with atezolimumab plus bevacizumab and radiation therapy to the clivus. Discussion(s): The incidence of HCC has almost tripled since the 1980s making it the fastest rising cause of cancer related deaths. Metastasis to the brain comprises 0.26% to 2.2% of cases and the skull base is the most rarely affected anatomical site. Although CNS presentation is rare, we may see more neurological manifestations of metastatic HCC with the persistence of chronic hepatitis infections, the rise of metabolic diseases such as NASH, and an increase in alcohol-related liver disease during the COVID-19 pandemic. Although exceedingly rare, metastasis to the clivus should be considered in the differential diagnosis of skull base masses. Despite detection and treatment, prognosis remains poor and emphasis should be placed on consistent HCC surveillance. This case emphasizes that skull masses must be evaluated diligently as they can be the first sign of underlying liver malignancy. Given the morbidity and mortality associated with HCC, recognition of atypical manifestations of HCC can lead to a prompt diagnosis and initiation of life-saving treatment. (Figure Presented).

Tackling hepatitis B co-infection in PLHIV after COVID: an audit and updated guidelines

Background: 5-20% of people living with HIV (PLWH) are co-infected with Hepatitis B (HBV) and coinfection is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), incidence of which is 5 to 6 times higher. COVID-19 led to a lapse in surveillance of this population, warranting a reassessment. Method(s): BHIVA and EACS guidelines were combined to create a standard to audit against. All people under the care of the HIV team with co-infection were included, and analysed for the prior six months. Local ethics approval was granted. The results were then presented to clinicians, and local guidelines created to reflect the most recent research on co-infection which were shared with the department. A re-audit was then conducted against the modified guidelines. Result(s): 42 people were living with co-infection of HBV and HIV, with a 50:50 gender split;32 were of Black African ethnicity (76%). The median age was 50.5. Nobody had a HBV resistance profile done at baseline. 3 people did not have suppressed HIV viral load (VL), and 8 people did not have a suppressed HBV VL. In the previous 6 months only 26 (62%) had had a HBV VL, 20 (48%) had had an alfa-fetoprotein (AFP) check, and 21 (36%) had had an ultrasound liver. An US had been requested in 21 (50%) of patients. 100% were on a tenofovir-containing drug regimen. Following presentation and rewriting of guidelines, performance of investigations improved. An US had been requested in 26 (62%) cases although only performed in 16 (38%) and an AFP had been measured in 25 (60%). Vaccination of partners had also improved. Conclusion(s): The provision of care of those with coinfection was significantly impacted by the COVID pandemic, but reinforcement of information, and re-issuing of guidelines improved patient care. Attendance of appointments for blood tests and scans remains a major challenge for improving patient care. Literature aimed at our local population to reinforce the importance of HCC screening is being developed.

Nanopore single-molecule analysis of biomarkers: Providing possible clues to disease diagnosis

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic COVID-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.Copyright © 2023 Elsevier B.V.

The importance of vaginoscopy in premenarchal girls with vaginal bleeding- call for more PAG practioners

Introduction: Prepubertal vaginal bleeding outside the neonatal period is always abnormal and is very alarming to both parents and physicians. The variable etiologies of vulvovaginitis are the most common causes of vaginal bleeding during the prepubertal period. We report a series of three cases observed during covid" period of 2020-2022. Case report: two patients 8 and 9 year -old girls, were refered to pediatric secondary center due to of external vaginal bleeding. Hormonal levels were pre-pubertal and bone age was not advanced. Both girls were hospitalized and sellar X-ray and pelvic MRI were done during further course, not revealing the etiology of bleeding. Six months after the first bleeding, they were reffered to a pediatric gynecologist where foreign bodies (grass seed) were found during vaginoscopy. Third patient, a 3-year- old girl, was examined by her pediatrician because of heavy bleeding. Hormonal analysis and bone age were not suggestive of precocious puberty. Additional analyses revealed elevated alpha fetoprotein level (>5000 IJ,), which led to the diagnosis of yolk sac tumor in vagina wall, which was then confirmed by vagionoscopy and biopsy. It is important to perform vaginoscopy in premenarchal girls with repeated vaginal bleeding because in patients older than five years, a common reason for vaginal bleeding is foreign body but in younger patients, the primary goal is to exclude a malignant tumor.Copyright © 2023

Evaluation of fetuin-A, CRP, and CRP/fetuin-A values in COVID-19 patients

Objectives: Fetuin-A, a glycoprotein with several functions, is also a negative acute phase reactant. The purpose of this study was to investigate levels of serum fetuin-A in coronavirus disease 2019 (COVID-19) patients, its association with disease severity, and whether it has superiority over C-reactive protein (CRP). Methods: The research comprised 56 individuals with COVID-19(+) and 30 healthy controls. The COVID-19(+) patient population was split into three subgroups: mild, moderate, and severe. All participants' serum concentrations of fetuin- A, tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6) were measured using ELISA commercial test kits. In addition, CRP and other biochemical values from biochemistry laboratory data were gathered, and the CRP/fetuin-A ratio was calculated. Results: The fetuin-A concentration of the COVID-19(+) patient group was shown to be statistically lower than that of the healthy control group. TNF-a and IL-6 levels were found to be significantly different in both groups. While fetuin-A had a higher area under the curve (AUC) value than CRP (0.875 and 0.800, respectively), CRP/fetuin-A had the strongest AUC (0.933). Conclusion: Low serum fetuin-A concentrations in COVID-19 patients suggest that fetuin-A is a negative acute phase reactant for severe acute respiratory syndrome coronavirus 2. Furthermore, fetuin-A alone and CRP/fetuin-A value are both contenders for being more remarkable markers than CRP.

Response assessment and clinical efficacy of 188Re-NDEDC/ Lipiodol trans-arterial Radionuclide therapy (TART) in patients with Hepatocellular carcinoma: A prospective single center study

Aim/Introduction: Inoperable HCC patients with multifocal lesions and malignant portal vein thrombosis (PVT) have poorer prognosis with limited treatment options. 188Re-N-DEDC lipiodol is an emerging agent for such cases due to its simple and on-site labelling procedure, cost-effectiveness and least radiation induced side effects. We aimed to explore the response assessment, safety and efficacy of 188Re-N-DEDC-lipiodol in multifocal HCC with/without PVT. Material(s) and Method(s): Radiologically and biochemically confirmed HCC patients with/without PVT having ECOG performance status <=2 and Child Pugh score A /B were recruited. Baseline serum alpha-fetoprotein (AFP) was obtained for biochemical correlation and follow-up. After lipiodol labelling & QC checks, therapeutic activity of 188Re-N-DEDC/lipiodol were injected under fluoroscopic guidance through femoral branch in super-selective artery of tumor. Post-therapy planar and SPECT/CT imaging were performed at 2, 6, 12, 24, 48 and 72hrs to see tumoral retension. Response was assessed at 2 months post-therapy by mRECIST criteria and S. AFP level. Clinical & biochemical toxicities were graded by CTCAE v5.0. Result(s): Thirty-One (31) patients (27 male;4 female) with mean age 55.9 +/- 9.78 years have been recruited for therapy. Overall mean injected activity of 188Re-N-DEDC lipiodol was 2.9+/-0.9GBq (78.4+/-24.2mCi). The median follow-up period was of 6 months. One patient was lost to follow-up due to prevailing COVID situations and 3 patient died before follow-up due to internal variceal bleeding, so radiological and biochemical response were assessed only in 27/31 patients by mRECIST criteria and serum AFP tumor marker level respectively. Radiologically, objective response rate was seen in 12/27 patients (~45%) and disease control rate was seen in 20/27 patients (~74%). 6/27 patients had non-AFP producing tumor i.e. serum AFP were normal at baseline and follow-ups while in remaining 21 patients, biochemical objective response rate was seen in 11/21 patients (~52%) and disease control rate was 14/21 patients (~67%). Post-therapy clinical toxicities (Nausea, Vomiting, Fever, abdominal pain) were observed in most of the patients for 2-3 days and were treated symptomatically. One patient showed grade 3 liver toxicity & progressive worsening of LFT, 20 patients showed grade 1 derangements in liver enzymes & 6 patients showed grade 2 derangements in liver enzymes. Hematological toxicities were seen in 4 patients (<=Grade 2 in 2 patients & grade 3 in two patients). Conclusion(s): In patients of HCC with/without PVT, trans-arterial Re188-N-DEDC/lipiodol therapy proved to be safe and effective with good disease control.

Assessment the levels of fibroblast growth Factor 21, Fetuin-A and lipid profile in patients with COVID-19 after infection

Objective: We evaluated Fetuin-A, FGF-21 and lipid profiles in the serum of recovered patients from coronavirus disease 2019 (COVID-19).

Alpha-Fetoprotein-Producing Gastric Cancer With Delayed Diagnosis Caused by COVID-19: A Case Report.

A 70-year-old man was diagnosed with coronavirus disease 2019 (COVID-19). The patient had suspected upper gastrointestinal bleeding during the course of the COVID-19 infection. Urgent esophagogastroduodenoscopy (EGD) was performed. However, because of mobility restrictions imposed as a COVID-19 countermeasure, EGD was done in a small hospital room. Hemostatic treatment was successful, but no sufficient close examination could be done. The patient, who was diagnosed as having alpha-fetoprotein-producing gastric cancer, died about three months later.

Neonatal Acute Liver Failure in a Preterm Neonate with Gestational Alloimmune Liver Disease and Congenital Portosystemic Shunts

Introduction: Gestational alloimmune liver disease (GALD) is a leading cause of neonatal acute liver failure (NALF), a rare but important diagnosis. Congenital portosystemic shunts (CPSs) are rare vascular anomalies that leave patients at risk for developing a wide spectrum of complications and have not been previously associated with GALD. In this case, we present a newborn male with NALF secondary to GALD complicated by intrahepatic shunts. Case Description: The patient is a 30 weeks gestational age male born to a 28-year-old gravida 2 para 0 mother via urgent cesarean section for severe placental malperfusion. The pregnancy was complicated by severe intrauterine growth restriction, oligohydramnios, and maternal COVID-19 infection. The patient's initial NICU course was remarkable for respiratory distress requiring ventilatory support, hypotension requiring inotropes and stress dose steroids, and coagulopathy with bleeding requiring transfusion of multiple blood products. An abdominal ultrasound showed large congenital intrahepatic portosystemic shunts. Over the course of the hospitalization, the infant progressed to fulminant hepatic failure with associated coagulopathy, hypoalbuminemia, direct hyperbilirubinemia, and hyperammonemia. There was persistent anasarca in addition to elevated ferritin (1,922 ng/dL) and alpha-fetoprotein (97,855 ng/mL). Serial SARS-CoV-2 NAAT were negative. In consultation with the hepatologist there was high clinical suspicion for GALD, and treatment with intravenous immunoglobulin was initiated, however, no clinical or laboratory improvement was noted. Abdominal MRI showed progression of the large CPSs and enlargement of the hepatic arteries. The infant continued to deteriorate, was transitioned to comfort care, and died on day of life 82. A limited autopsy revealed a markedly edematous and jaundiced male with grossly enlarged liver with hepatocellular cholestasis, portal fibrosis, diffuse hepatobiliary iron depositions, and C5b9 positivity within hepatocytes confirming a diagnosis of GALD. Discussion: Neonatal hemochromatosis is the phenotypic result of severe liver injury leading to iron overload and extrahepatic siderosis, the mechanism of hepatic injury now recognized in GALD. Liver failure in newborns with GALD often presents with marked coagulopathy, hypoalbuminemia, and edema with and without ascites. The establishment of the diagnosis is crucial given without treatment, the prognosis is very poor. There have been no case reports of neonates with acute liver failure from CPSs or CPSs occurring with GALD. We hypothesize that the presence of CPSs worsens the clinical course of GALD through an unknown mechanism that further expedites hepatocellular damage. Furthermore, the role of SARS-CoV-2 infection and transmission in the neonatal population is still unknown. Conclusion: Neonatal acute liver failure caused by GALD is a rare but potentially fatal diagnosis. CPSs associated with GALD have not been previously documented. This case demonstrates the interplay of these disease entities likely contributing towards a more severe course of NALF and highlights the importance of early identification for guiding management. (Figure Presented).

RARE CASE OF ILEOCOLIC MESENTERY PRIMARY MELANOMA WITH LIVER METASTASIS

Purpose/Background: Although GI melanoma is commonly a metastatic disease, it is very unusual to see the mesenteric mass of the cecum and terminal ileum as the primary origin of melanoma. Hypothesis/Aim: This is a case report and presentation showing a rare occasion of primary melanoma in the cecum and the terminal ileum mesentery along the ileocolic pedicle causing cecal complete bowel obstruction. Methods/Interventions: The reported case is a rare occasion of large bowel obstruction near the cecum resulted from primary mesenteric melanoma invading into the wall of the descending colon. Primary melanoma of the GI tract is still controversial and only a limited of cases have been reported in the literature. We added a review of the other published case reports to this case report using Endnote. Results/Outcome(s): This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt this was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. This is a 68-year-old female who was seen in the outpatient setting with increasing abdominal girth in addition to nausea and vomiting and obstipation. The patient had alternating bowel habits for over 2 months which she felt was related to Covid as she was tested Covid positive and diagnosed with Covid pneumonia at the same time. She was directly admitted from the office to the inpatient service and she had a CAT scan of the abdomen pelvis that demonstrated cecal obstruction related to possibly cecal mass/ mesenteric mass with multiple liver metastatic diseases. She underwent exploratory laparotomy which resulted in Right extended hemicolectomy en bloc with a loop of jejunum and part of the terminal ileum. She had also intraoperative liver biopsy that demonstrated metastasis of the melanoma to the liver. We tested later serum S100 the protein and it was elevated to 18,000, she had serum negative alpha-fetoprotein and negative CEA. Limitations: Case report study with reported cases reviewed. Conclusions/Discussion: Large bowel obstruction could be related to unusual diagnoses like melanoma of the bowel mesentery. Although, primary GI melanoma is rare this showed the possibility of such diagnosis. (Figure Presented).

BEDSIDE TEST TO RULE OUT AN ECTOPIC PREGNANCY USING A MODIFIED FDA APPROVED KIT

OBJECTIVE: To evaluate the accuracy of a modified bedside test in ruling out an ectopic pregnancy. The test is based on a lateral flow immunoassay for alpha-fetoprotein (AFP). It has been shown that a high AFP level in vaginal blood indicates the passage of fetal tissue, suggestive of a miscarriage [1].We hypothesized that high AFP levels in sampled intrauterine tissue, assuming non-heterotopic pregnancy, rules out the presence of an ectopic pregnancy. MATERIALS AND METHODS: This is a prospective cohort study. The study included pregnant women undergoing a dilation and curettage (D&C) for pregnancy loss or termination, women with pregnancy loss or an ectopic pregnancy presenting with vaginal bleeding, and non-pregnant women with vaginal bleeding. Vaginal blood was collected on gauzes, sanitary pads, and cotton swabs. Samples were then tested for AFP levels using a commercial kit (ROMplus, Laborie, USA) originally designed to detect leakage of amniotic fluid. This kit contains a lateral flow immunoassay strip capable of detecting the presence of AFP. Positive samples for AFP were retested at a later date (after 3 to 20 days) to ascertain the stability of AFP and reliability of the test. Official sonograms, pregnancy tests, and final pathology results were obtained to confirm pregnancy status as well as the presence or absence of fetal tissue in the vaginal blood. A sensitivity and specificity analysis was performed against these final results to validate the accuracy of the test strip in ruling out an ectopic pregnancy. RESULTS: A total of 30 vaginal blood samples were tested for AFP. All pregnant women who had a miscarriage or D&C had detectible AFP in their vaginal blood (n=13). On retesting the samples 3 to 20 days later, these results remained the same (positive test strip). The remaining 17 vaginal blood samples were from 4 women with ectopic pregnancies and from 13 non-pregnant women with vaginal bleeding. All 4 ectopic pregnancies had no AFP detected in the vaginal blood and only 1 out of 13 non-pregnant patient samples had AFP detected. The ROMplus test strip correctly detected AFP in all samples tested containing fetal tissue (n=13) resulting in a test sensitivity of 100%. ROMplus correctly identified the absence of AFP in 16 out of the 17 samples lacking fetal tissue, a 94% test specificity. CONCLUSIONS: ROMplus has the potential to accurately and reliably detect the presence of AFP, and hence fetal tissue, in vaginal blood samples. This could be a vital non-invasive aid in ruling out an ectopic pregnancy at the bedside (currently off-label use). Furthermore, it could limit the amount of invasive testing and visits needed in cases of pregnancies of unknown location. IMPACT STATEMENT: In light of the recent COVID-19 pandemic, a simple non-invasive bedside test to rule out an ectopic pregnancy is highly desired given its potential for reducing the number of visits, investigations performed, and personnel involved in the workup of a pregnancy of unknown location.

Rupture of membranes self-assessment

Objective: An accurate tool to self-assess rupture of membranes (ROM) could decrease the need for hospital visits during the COVID pandemic. Our objectives were to evaluate the agreement between patients’ and researchers’ interpretation of a test for ROM using a modified FDA approved device and to evaluate patients’ level of difficulty interpreting the test. Study Design: A prospective cohort study of women complaining of leakage of fluid at ≥20 weeks gestation. Women wore sanitary pads with a modified lateral flow alpha-fetoprotein immunoassay strip to detect ROM. The strip was obtained from the FDA approved ROM Plus kit (Laborie/Clinical Innovations). Another set of pads was instilled with their urine. Patients and investigators interpreted the tests as positive (2 bars), negative (1 control bar), and other (not activated [no bars] or invalid [partial or unclear bars]). Cohen’s kappa was used to measure the agreement between patients and researchers. Difficulty interpreting the test was graded by patients on a scale of 1-10 (1 = least difficult, 10 = most). Results: Twenty-one women were recruited: 19 had ROM confirmed by clinical assessment, and 2 had ROM ruled out. Fifty-four pads were tested (women could wear more than 1 pad). Of the 26 worn by women with confirmed ROM, 20 (76.9%) were positive, none (0%) were negative, 3 [11.5%] were invalid and 3 [11.5%] were not activated. Of the 24 urine instilled pads from women with confirmed ROM, 4 (16.7%) were positive, 18 (75%) were negative and 2 (8.3%) were not activated. The women with ROM ruled out had non-activated tests (2 dry worn pads) and their urine instilled on 2 additional pads showed negative results. Cohen’s kappa was 0.85.Weighted kappa 0.88. The mean level of difficulty interpreting the test was 1.64. Conclusion: The modification of the FDA approved test did not result in false positive or negative results and 81.5% gave definitive results. Patients and researchers had a near perfect agreement interpreting the test. Women can easily interpret this self-test. [Formula presented] [Formula presented]

Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.