Skull Metastasis With Orbital Invasion as a Primary Manifestation of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common worldwide cancer with a poor prognosis despite treatment advancements. Patients typically exhibit signs and symptoms pertaining to the liver. Extrahepatic metastasis of HCC is documented to be as low as 5% of cases. Bone metastasis ranks third following lungs and regional lymph nodes. The typical locations for bone metastasis include the vertebral column, pelvis, femora, and ribs, with skull metastasis, being reported in less than 1.6% of cases. Herein, we describe a case of HCC presenting with skull metastases and orbital invasion as the initial manifestation.

New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid.

Leptomeningeal carcinomatosis represents a terminal stage and is a devastating complication of cancer. Despite its high incidence, current diagnostic methods fail to accurately detect this condition in a timely manner. This failure to diagnose leads to the refusal of treatment and the absence of clinical trials, hampering the development of new therapy strategies. The use of liquid biopsy is revolutionizing the field of diagnostic oncology. The dynamic and non-invasive detection of tumor markers has enormous potential in cancer diagnostics and treatment. Leptomeningeal carcinomatosis is a condition where invasive tissue biopsy is not part of the routine diagnostic analysis, making liquid biopsy an essential diagnostic tool. Several elements in cerebrospinal fluid (CSF) have been investigated as potential targets of liquid biopsy, including free circulating tumor cells, free circulating nucleic acids, proteins, exosomes, and even non-tumor cells as part of the dynamic tumor microenvironment. This review aims to summarize current breakthroughs in the research on liquid biopsy, including the latest breakthroughs in the identification of tumor cells and nucleic acids, and give an overview of future directions in the diagnosis of leptomeningeal carcinomatosis.

The Addition of Systemic Terbinafine to Antifungal Combination Therapy in the Treatment of Disseminated Drug-Resistant Mold Infections in a National Cancer Institute Comprehensive Cancer Center: A Six-Year Study.

Introduction Combination antifungal regimens are frequently employed in the treatment of invasive fungal infections in patients who are immunocompromised, particularly for cancer and transplant patients. Terbinafine is a potential agent of interest for combination regimens. Methods We reviewed data over a six-year period examining patient outcomes in terms of both mortality and distribution of pathogens. The total number of patients in our study was 64. The use of terbinafine versus no terbinafine in combination therapy was assessed. Of the 64 patients analyzed, only 14 received terbinafine. Mortality was calculated for both groups, and demographics were analyzed by descriptive statistics. Results There was no statistical difference in mortality outcomes in either group. The addition of terbinafine was well tolerated and did not appear to result in any undue toxicity concerns. Discussion We wish to draw greater attention to this potential agent within our armamentarium for invasive fungal infections. To our knowledge, the total number of patients in our study, while small, represents the largest reported cohort in the literature to date. Sensitivities are crucial to be obtained for fungal pathogens as this likely undermined the utility of terbinafine in our study with larger than expected numbers of multidrug-resistant Fusarium. With limited patient numbers, a multicenter trial would be beneficial to further examine terbinafine in combination regimens.

Immunoradiation Therapy for End-Stage Undifferentiated Cervical Cancer That Restored Sensitivity to Chemotherapy and Resulted in the Disappearance of the Cancer.

Among cervical cancers, small cell undifferentiated carcinoma is rare. Because of its rapid progression, the prognosis is extremely poor. During the course of cisplatin-based chemotherapy for stage Ⅳ small cell undifferentiated carcinoma of the cervix, the patient developed drug resistance, and standard treatment was no longer feasible. Therefore, immunoradiotherapy was administered to activate anticancer immunity. Surprisingly, the cancer drug sensitivity was restored, and cisplatin was again successful, and the cancer disappeared. In addition, the activation of cancer-specific immunity maintained the disappearance of the cancer. It should be noted that immunoradiotherapy not only increases anti-cancer immunity but may also contribute to overcoming cancer drug resistance.

Development of a robust cell-based potency assay for a coxsackievirus A21 oncolytic virotherapy.

Oncolytic viruses (OV) are part of a burgeoning field of investigational oncolytic therapy (OT), in which lytic viruses dissolve advanced tumors productively and specifically. One such OT is a Coxsackievirus A21 (CVA21) based OV that is currently under clinical evaluation. A tissue culture infectious dose (TCID50) assay was used for CVA21 potency release and stability testing in early clinical development. The titer measured in this method was an extrapolated value from cytopathic effect (CPE) observed during the serial dilution but doesn't represent direct viral killing of cells. Moreover, the assay was not deemed to be optimal to carry into late phase clinical development due to limitations in assay precision, turn-around time, and sample throughput. To address these points, we developed a plaque assay to measure viral plaque forming units to measure the potency value for drug substance (DS), drug product (DP) and virus seed (master and working) stocks. In this manuscript, we describe the steps taken to develop this plaque assay for the late-stage clinical development, which include the assay qualification, validation, and robustness protocols, and describe statistical methods for data analysis. Moreover, the method was validated for linearity, accuracy, precision, and specificity. Furthermore, the plaque assay quantifies OV infectivity with better precision (32% vs 58%), with higher sample throughput (22 samples/week vs 3 samples/week) and shorter assay turnaround time (4 days vs 7 days) than the TCID50 method. This assay development strategy can provide guidance for the development of robust cell-based potency methods for OVs and other infectious viral products.

Electronic health intervention to manage symptoms of immunotherapy in patients with cancer (SOFIA): Results from a randomized controlled pilot trial.

BACKGROUND: For patients receiving immune checkpoint inhibitors, early detection of immune-related adverse events (irAEs) is critical for one's safety. To this end, a smartphone app (SOFIA) was developed that featured the assessment of electronic patient-reported outcomes (ePROs) focusing on irAEs as well as a set of comprehensive supportive information. Its feasibility and preliminary efficacy were evaluated in a randomized controlled trial (RCT). METHODS: Patients who received immune checkpoint inhibition therapy were randomly assigned to an intervention group (IG) or a control group (CG; care as usual). During the 12-week intervention period, IG patients used SOFIA to report twice weekly ePROs and receive cancer- and immunotherapy-relevant contents. Before a patient's next clinical visit, the physician in charge was given the ePRO reports. The primary objective was to test the feasibility of SOFIA. Furthermore, the preliminary efficacy of SOFIA for health-related quality of life (HRQOL), psychosocial outcomes, and medical data was examined. Clinical outcomes were assessed at baseline (T0), post-intervention (T1), and a 3-month follow-up (T2). RESULTS: Seventy-one patients were randomized to the IG (n = 34) or the CG (n = 37). SOFIA showed high feasibility and acceptance. At T1, patients in the IG reported significantly better HRQOL and role functioning and less depression, distress, and appetite loss. No significant differences were revealed regarding medical data, the utilization of supportive care services, or survival. CONCLUSIONS: SOFIA showed high feasibility and acceptance and improved HRQOL and psychosocial outcomes. These results suggest further evaluation of efficacy in a large-scale confirmatory multicenter RCT.

Maxillary interim obturator prosthesis fabrication for a patient with limited mouth opening with a digital approach: A clinical report.

Squamous cell carcinoma is a common malignant condition affecting the oral cavity and may involve the surrounding maxillofacial regions. Treatment commonly involves resection of the tumor, followed by prosthetic rehabilitation of the resection defect. This clinical report presents a 62-year-old Asian male patient who had previously undergone surgical resection, resulting in a post-surgical Aramany Class II maxillary defect. The patient's medical history included severe trismus, characterized by restricted mouth opening, as well as a diagnosis of maxillary sinus verrucous squamous cell carcinoma. This report provides a comprehensive account of the rapid fabrication of an interim obturator using digitally assisted dentistry techniques.

Outcomes of Simultaneous Versus Staged Resection for Stage IV Colorectal Cancer with Synchronous Liver Metastases.

INTRODUCTION: Management of stage IV colorectal cancer with synchronous liver metastases remains debated, as colorectal and liver resections can be performed simultaneously or staged apart. OBJECTIVE: This study aims to determine any demographic or outcome differences between simultaneous and staged resection. PARTICIPANTS: Retrospective review was performed on patients diagnosed with synchronous colorectal primary and liver metastases within Southern California Kaiser Permanente (KP) hospitals between 2010 and 2020. Patients with other metastases on diagnosis or those who did not receive both primary and liver resections were excluded. Demographic and outcome data were collected and analyzed. RESULTS: Of the 113 patients who met criteria, 72 (63.7%) received simultaneous and 41 (36.3%) received staged resection. Demographic data were comparable between simultaneous and staged resection, respectively, including median age of diagnosis, sex, and race. Both groups had similar median length of stay, percentage of major colorectal resection, and percentage of major liver resection. Both groups also had similar rates of radiation therapy, chemotherapy, and immunotherapy. There were no statistically significant difference in complications rates, median follow-up time, median overall survival, and median disease-free survival. CONCLUSIONS: Practice patterns within Southern California KP hospitals favor minor colorectal and liver resections. However, there were no significant differences in demographics, treatment rates, or outcomes between simultaneous and staged resection. While not statistically significant, our findings of a 11.9% higher major liver resection rate and 7.5-month longer median disease-free survival in the staged resection group may benefit from further study with higher power datasets.

Hepatic Ablation Technology: Assessment of Conflicts of Interest in Recent Literature.

INTRODUCTION: Collaboration between the health care industry and surgeons is critical in modern medicine. Conflict of interest (COI) has the risk of introducing bias into research studies. We investigated the accuracy of self-disclosed COI for studies that researched the use of microwave ablation for liver metastasis. METHODS: A literature search identified studies that investigated the use of microwave ablation for liver cancer between 2016 and 2022. We utilized the Open Payments Database to query individual authors' financial contributions from the industry. The accuracy of the disclosure statement and financial contribution for each study and author was calculated. We compared the amount of financial contribution authors received based on the accuracy of their COI statement. RESULTS: Twenty-five studies of interest were identified. The mean number of authors was 8.24. A disclosure statement was present in 52% of studies. Of those, 28% had an incongruent disclosure statement. 9/25 (36%) of studies had a conflict of interest based on financial payments provided by industry. Overall, authors received an average of $440,483.41 (SD $1,889,375.34). We did not find a difference in the financial contribution's value based on the disclosure statement's accuracy (P = .55). CONCLUSIONS: Over a quarter of studies in our review of microwave ablation literature had discrepancies in the reporting of conflicts of interest, highlighting the need for improved reporting of potential conflicts of interest to protect the integrity of clinical research. Compared to other fields of surgery, we found a lower rate of undisclosed COI, suggesting that the scope of cancer-directed surgery may be more resistant to industry influence.

Surgical treatment of invasive fungal infection in pediatric oncology.

BACKGROUND: Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. METHODS: Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome. RESULTS: From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days. CONCLUSIONS: Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy.

Social robotics as an adjuvant during the hospitalization process in pediatric oncology patients.

OBJECTIVE: To describe the experience of implementing social robotics as an adjuvant during the hospitalization process in pediatric oncology patients. METHODS: Before and after cohort study, applying an intervention with the Lego Mindstorms EV3 kit in patients between 8 and 17 years old that are hospitalized with a cancer diagnosis. We excluded patients from the intensive care unit or when their treating physician recommended so. The intervention consisted of a three-phase workshop: an open architecture story, building a car robot using the Lego Mindstorm EV3 kit, and cooperative playing activities such as races and passing obstacles. RESULTS: Thirteen patients received the intervention with robotic lego. The median age was 15 years (IQR = 3), and 84.6% of the population (n = 11) were male. We found significant improvement in the language (topic management p = .011 and communicative intention p = .034). Other characteristics improved, but not significantly (self-care activities index, catching). No adverse events occurred during the intervention. CONCLUSIONS: The results of this pilot study suggest that implementing social robotics during hospitalization in children with cancer is a therapeutic adjuvant and safe intervention that promotes better communication, self-care, and a physical activity improvement. For future studies, the impact of this intervention could be measured in hospitalized pediatric cancer patients.

Perioperative psychological distress in patients with intracranial tumors; a single center study.

PURPOSE: Distress Thermometer (DT) was adopted to evaluate distress in neuro-oncology on a scale from 1 to 10. DT values above 4 indicate major distress and should initiate psycho(onco)logical co-therapy. However, data about peri-operative distress is scarce. Hence, we evaluated peri-operative distress levels in a neurosurgical patient cohort with various intracranial tumors using the DT. METHODS: We conducted a retrospective study including inpatients with brain tumors who underwent surgery in our department between October 2015 and December 2019. Patients were routinely assessed for distress using the DT before or after initial surgery. A comparative analysis was performed via Wilcoxon rank-sum test. RESULTS: 254 patients were eligible. Mean DT value of the entire cohort was 5.4 ± 2.4. 44.5% (n = 114) of all patients exceeded DT values of ≥ 6. In our cohort, poor post-operative neurological performance and occurrence of motor deficits were significantly associated with major distress. When analysed for peri-operative changes, DT values significantly declined within the male sub-cohort (6.0 to 4.6, p = 0.0033) after surgery but remained high for the entire cohort (5.7 and 5.3, p = 0.1407). Sub-cohort analysis for other clinical factors revealed no further significant changes in peri-operative distress. CONCLUSION: Distress levels were high across the entire cohort which indicated a high need for psychological support. Motor deficits and poor post-operative neurological performance were significantly associated with DT values above 6. Distress levels showed little peri-operative variation.

Proteomic profiles of peritoneal-derived small extracellular vesicles correlate with outcome in ovarian cancer patients.

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, two patient cohorts were enrolled, including OvCa cases who underwent a diagnostic or cytoreductive surgery, and non-oncological patients as controls, who underwent abdominal surgery for benign gynecological conditions. PFD-sEVs systematic extraction from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEVs proteomic profiles in high-grade serous ovarian carcinomas (HGSOC) revealed two clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of the PFD-sEVs content provided a prognostic value with potential implications in HGSOC clinical management.

Efficacy of computer-assisted robotic based clinical training program for spinal oncology education on pedicle screw placement.

Pedicle screw placement (PSP) is the fundamental surgical technique that requires high accuracy for novice orthopedists studying spinal oncology education. Therefore, we set forth to establish a computer-assisted robotic navigation training program for novice spinal oncology education. Novice orthopedists were involved in this study to evaluate the feasibility and safety of the computer-assisted robotic navigation (CARN) training program. In this research, trainees were randomly taught by the CARN training program and the traditional training program. We prospectively collected the clinical data of patients with spinal tumors from 1st May 2021 to 1st March 2022. The ability of PSP was evaluated by cumulative sum (CUSUM) analysis, learning curve, and accuracy of pedicle screws. The patients included in both groups had similar baseline characteristics. In the CUSUM analysis of the learning curve for accurate PSP, the turning point in the CARN group was lower than that in the traditional group (70th vs. 92nd pedicle screw). The LC-CUSUM test indicated competency for PSP at the 121st pedicle screw in the CARN group and the 138th pedicle screw in the traditional group. The accuracy of PSP was also significantly higher in the CARN group than in the traditional group (88.17% and 79.55%, P = 0.03 < 0.05). Furthermore, no major complications occurred in either group. We first described CARN in spinal oncology education and indicated the CARN training program as a novel, efficient and safe training program for surgeons.

Oncologists' perceptions of tumor genomic profiling and barriers to communicating secondary hereditary risks to African American cancer patients.

BACKGROUND: Tumor genomic profiling (TGP) identifies targets for precision cancer treatments, but also secondary hereditary risks. Oncologists are poorly trained to communicate the results of TGP, especially among patients with lower health literacy, poorer genetics knowledge, and higher mistrust. African American (AA) patients are especially vulnerable to poor understanding due to significant cancer disparities and lower uptake of TGP. The goal of this research is to inform the development of an internet-based brief educational support for oncologists to prepare them to provide better decisional support related to TGP for their AA cancer patients. METHODS: This mixed-methods study used semi-structured interviews of oncologists to inform development of an online survey with a convenience sample of US-based oncologists (n = 50) to assess perceptions of the challenges of TGP and communicating results to AA patients. RESULTS: Most interviewed oncologists felt it was important to consider racial/cultural differences when communicating about hereditary risks. Cost, family dynamics, discrimination concerns, and medical mistrust were identified as particularly salient. Survey respondents' views related to AAs and perceptions of TGP were strongly associated with years since completing training, with recent graduates expressing stronger agreement with statements identifying barriers/disadvantages to TGP for AA patients. CONCLUSIONS: Oncologists who had more recently completed training expressed more negative perceptions of TGP and more perceived challenges in communicating about TGP with their AA patients. Focused training for oncologists that addresses barriers specific to AAs may be helpful in supporting improved communication about TGP and improved decisional support for AA patients with cancer considering TGP to evaluate their tumors.

Metabolic dysfunction-associated profiles and subsequent site-specific risk of obesity-related cancers among Chinese patients with diabetes: a retrospective cohort study.

OBJECTIVES: To compare metabolic dysfunction-associated profiles between patients with diabetes who developed different obesity-related site-specific cancers and those who remained free of cancer during follow-up. DESIGN: Retrospective cohort study. SETTING: Public general outpatient clinics in Hong Kong. PARTICIPANTS: Patients with diabetes without a history of malignancy (n=391 921). PRIMARY OUTCOME MEASURES: The outcomes of interest were diagnosis of site-specific cancers (colon and rectum, liver, pancreas, bladder, kidney and stomach) during follow-up. Cox proportional hazards regression was applied to assess the associations between metabolic dysfunction and other clinical factors with each site-specific cancer. RESULTS: Each 0.1 increase in waist-to-hip ratio was associated with an 11%-35% elevated risk of colorectal, bladder and liver cancers. Each 1% increase in glycated haemoglobin was linked to a 4%-9% higher risk of liver and pancreatic cancers. While low-density lipoprotein cholesterol and triglycerides were inversely associated with the risk of liver and pancreatic cancers, high-density lipoprotein cholesterol was negatively associated with pancreatic, gastric and kidney cancers, but positively associated with liver cancer. Furthermore, liver cirrhosis was linked to a 56% increased risk of pancreatic cancer. No significant association between hypertension and cancer risk was found. CONCLUSIONS: Metabolic dysfunction-associated profiles contribute to different obesity-related cancer outcomes differentially among patients with diabetes. This study may provide evidence to help identify cancer prevention targets during routine diabetes care.

The experiences of men on active surveillance for prostate cancer and their significant others: A qualitative synthesis.

BACKGROUND: Active surveillance (AS) for prostate cancer (PCa) is a monitoring pathway for men with low-grade, slow growing PCa and aims to delay or avoid active treatment by treating only in the case of disease progression. Experiences of this pathway vary but living with an untreated cancer can have a negative psychological impact on both the patient and their significant other (SO). Literature suggests partners are the primary source of support for men on AS, and therefore it is important to consider SO experiences alongside those of the patient. To the best of our knowledge this is the first UK-based qualitative review looking specifically at experiences of AS for both men with PCa and their SOs. METHODS: MEDLINE (Ovid), EMBASE, PsychINFO, CINAHL and Cochrane Library were searched for literature reporting qualitative experiences of AS for PCa for either men on AS or SOs (or both). 2769 records were identified and screened, with 28 meeting the eligibility criteria. Qualitative data were synthesised and included men on AS (n = 428), and SOs (n = 51). RESULTS: Experiences of the AS pathway vary but reports of uncertainty and anxiety were present in the accounts of both men on AS and SOs. SOs are intertwined throughout every part of the PCa journey, and couples presented as a unit that were on AS together. Both patients and SOs expressed a need for more support, and highly valued peer support. Despite this finding, men expressed a dislike towards 'support groups'. CONCLUSIONS: Increased recognition in clinical practice of SO involvement in AS is needed. Further research is required to explore the specific types of support that would be most acceptable to this population to address the unmet support needs uncovered in this review.

'Just Google it'-A scoping review of online mental health resources for survivors of breast cancer.

OBJECTIVE: As the Internet is a ubiquitous resource for information, we aimed to replicate a patient's Google search to identify and assess the quality of online mental health/wellbeing materials available to support women living with or beyond cancer. METHODS: A Google search was performed using a key term search strategy including search strings 'cancer', 'wellbeing', 'distress' and 'resources' to identify online resources of diverse formats (i.e., factsheet, website, program, course, video, webinar, e-book, podcast). The quality evaluation scoring tool (QUEST) was used to analyse the quality of health information provided. RESULTS: The search strategy resulted in 283 resources, 117 of which met inclusion criteria across four countries: Australia, USA, UK, and Canada. Websites and factsheets were primarily retrieved. The average QUEST score was 10.04 (highest possible score is 28), indicating low quality, with 92.31% of resources lacking references to sources of information. CONCLUSIONS: Our data indicated a lack of evidence-based support resources and engaging information available online for people living with or beyond cancer. The majority of online resources were non-specific to breast cancer and lacked authorship and attribution.