Is Percutaneous Endoscopic Gastrostomy Tube Feeding Beneficial for Improving Survival in Patients With Dementia? A Systematic Review and Meta-Analysis of Current Pieces of Evidence

Dementia is a progressive, disabling neurogenic disease that results in serious nutritional deficiencies included dysphagia, malnutrition, and weight loss. The Percutaneous Endoscopic Gastrostomy (PEG) is a long-term enteral feeding method that is routinely used in demented patients with poor food intake as a standard protocol. However, most of the pieces of evidence have not shown the beneficial effects of PEG feeding on complications or survival rates in these patients. Some studies have even reported an increase in mortality. The current systematic review and meta-analysis aimed to evaluate the mortality rate and survival in primary demented patients with PEG. A systematic search was conducted on Pubmed and Scopus databases up to Aug 2019. The data were reviewed according to the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE). Based on the random-effects model, the mortality rate and median survival were expressed as risk ratio and weighted mean difference (WMD) and 95% CI, respectively. Among 13 included studies, PEG insertion in patients with primary dementia has no significant effect on 30-day, 90-day, 180-day, 1-year, and 2- year mortality rate or median survival (WMD: 9.77; 95% CI: -22.43 to 41.98; P=0.55). It seems that nasogastric tube (NGT) feeding in compared to PEG in this population is more effective. In conclusion, further prospective studies are needed for comprehensive evaluation of mortality or survival regarding comorbidities, underlying disease, cognitive and physical performance, and nutritional problems in demented patients.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver

Background and Objectives: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). Materials and Methods: Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included. The demographic and clinical data, radiological results and histopathological findings were reviewed and summarized. Results: We analyzed 36 patients comprising 6 PHL patients and 30 SHL patients. The median age at diagnosis tended to be younger in PHL than in SHL (59 vs. 63 years old, p = 0.349). Both entities had a small male predominance. The PHL patients tended to have higher levels of aspartate aminotransferase, alanine transaminase and serum albumin and lower levels of alkaline phosphatase, total bilirubin, γ-glutamyl transferase and lactate dehydrogenase compared with SHL, but there was no significant difference. Multiple mass lesions were the most common radiological finding in both groups. Diffuse large B-cell lymphoma was the predominant subtype in both groups (67% in PHL and 40% in SHL). The PHL patients had a longer median survival than the SHL patients (not reached vs. 3 months, p = 0.003). Conclusions: Although there was no significant difference between PHL and SHL in clinical, laboratory and radiological features, the SHL patients had very poor outcomes with a median survival time of 3 months. Effective therapies are urgently required for these patients.

Distribution of histopathologic types of primary pulmonary neoplasia in dogs and outcome of affected dogs: 340 cases (2010–2019)

OBJECTIVE To provide updated information on the distribution of histopathologic types of primary pulmonary neoplasia in dogs and evaluate the effect of postoperative adjuvant chemotherapy in dogs with pulmonary carcinoma. ANIMALS 340 dogs. PROCEDURES Medical records of dogs that underwent lung lobectomy for removal of a primary pulmonary mass were reviewed, and histopathologic type of lesions was determined. The canine lung carcinoma stage classification system was used to determine clinical stage for dogs with pulmonary carcinoma. RESULTS Pulmonary carcinoma was the most frequently encountered tumor type (296/340 [87.1%]), followed by sarcoma (26 [7.6%]), adenoma (11 [3.2%]), and pulmonary neuroendocrine tumor (5 [1.5%]); there was also 1 plasmacytoma and 1 carcinosarcoma. Twenty (5.9%) sarcomas were classified as primary pulmonary histiocytic sarcoma. There was a significant difference in median survival time between dogs with pulmonary carcinomas (399 days), dogs with histiocytic sarcomas (300 days), and dogs with neuroendocrine tumors (498 days). When dogs with pulmonary carcinomas were grouped on the basis of clinical stage, there were no significant differences in median survival time between dogs that did and did not receive adjuvant chemotherapy. CLINICAL RELEVANCE Results indicated that pulmonary carcinoma is the most common cause of primary pulmonary neoplasia in dogs; however, nonepithelial tumors can occur. Survival times were significantly different between dogs with pulmonary carcinoma, histiocytic sarcoma, and neuroendocrine tumor, emphasizing the importance of recognizing the relative incidence of these various histologic diagnoses. The therapeutic effect of adjuvant chemotherapy in dogs with pulmonary carcinoma remains unclear and warrants further investigation.

A 10-year Retrospective Study of Lung Cancer in Uganda

Background: Lung cancer is a leading cause of cancer-related deaths in Uganda. In this study, we aimed to describe the baseline characteristics and survival of patients with lung cancer at Uganda Cancer Institute (UCI). Methodology: We retrospectively reviewed medical records of all patients with a histological diagnosis of lung cancer registered at UCI between January 2008 and August 2018. Data on demographic, clinical, and treatment characteristics, and vital status were abstracted and analyzed. Patients with undocumented vital status on the medical records were contacted through phone calls. We determined survival as time from histological diagnosis to death. The Kaplan-Meier survival analysis was performed to estimate the median survival time and the 5-year overall survival rate. Results: Of the 207 patients enrolled, 56.5% (n=117) were female, median age was 60 years (range: 20-94), 78.7% (n=163) were never-smokers and 18 (8.7%) were living with HIV. Presumptive anti-tuberculosis treatment was given to 23.2% (n=48). Majority had non-small cell lung cancer (96.6%, n=200) with 74.5% (n=149) adenocarcinoma and 19% (n=38) squamous cell carcinoma. All had advanced (stage III or IV) disease with 96.1% (n=199) in stage IV. Chemotherapy (44.9%, n=93) and biological therapy (34.8%, n=72) were the commonest treatments used. Overall survival at 6 months, 1-, 2- and 5-years was 41.7%, 29.7%, 11.8% and 1.7% respectively. The median survival time was 4.4 months and was not different between NSCLC and SCLC (4.5 vs. 3.9 months respectively, p=.335). Conclusion: In Uganda, adenocarcinoma is the predominant histologic subtype of lung cancer predominantly occurring in females and non-smokers. Patients present late with advanced disease and poor overall survival. Public awareness should be heightened to facilitate early screening and improve outcomes.

The Crosstalk of Long Non-Coding RNA and MicroRNA in Castration-Resistant and Neuroendocrine Prostate Cancer: Their Interaction and Clinical Importance

Prostate cancer is featured by its heterogeneous nature, which indicates a different prognosis. Castration-resistant prostate cancer (CRPC) is a hallmark of the treatment-refractory stage, and the median survival of patients is only within two years. Neuroendocrine prostate cancer (NEPC) is an aggressive variant that arises from de novo presentation of small cell carcinoma or treatment-related transformation with a median survival of 1–2 years from the time of diagnosis. The epigenetic regulators, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been proven involved in multiple pathologic mechanisms of CRPC and NEPC. LncRNAs can act as competing endogenous RNAs to sponge miRNAs that would inhibit the expression of their targets. After that, miRNAs interact with the 3’ untranslated region (UTR) of target mRNAs to repress the step of translation. These interactions may modulate gene expression and influence cancer development and progression. Otherwise, epigenetic regulators and genetic mutation also promote neuroendocrine differentiation and cancer stem-like cell formation. This step may induce neuroendocrine prostate cancer development. This review aims to provide an integrated, synthesized overview under current evidence to elucidate the crosstalk of lncRNAs with miRNAs and their influence on castration resistance or neuroendocrine differentiation of prostate cancer. Notably, we also discuss the mechanisms of lncRNA–miRNA interaction in androgen receptor-independent prostate cancer, such as growth factors, oncogenic signaling pathways, cell cycle dysregulation, and cytokines or other transmembrane proteins. Conclusively, we underscore the potential of these communications as potential therapeutic targets in the future.

LONG-TERM OUTCOMES OF ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION (EUS-RFA) FOR ADVANCED PANCREATIC AND PERIAMPULLARY ADENOCARCINOMA

Background: Long term prognosis for pancreatic adenocarcinoma (PDAC) remains especially poor with an overall 5-year survival rate less than 9%. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding long-term outcomes of EUS-RFA for PDAC. In addition to thermal-induced coagulative necrosis and tissue damage, radiofrequency ablation (RFA) has potential to stimulate the host antitumor immunity. The aim of this study is to report long-term outcomes of EUS-RFA for unresectable PDAC. Methods: Retrospective chart review of adult patients with an established diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long term follow up (>30 months). Patients included in the review underwent a total of 1-4 RFA sessions using the Habib EUS-RFA radiofrequency catheter. All patients were concurrently undergoing standard of care chemotherapy. Results: 10 patients (median age 62 years, male 70%) underwent EUS-RFA (Table 1). Location of the primary PDAC was in the head (4), neck (2), body (2), and tail (2). A total of 22 RFA sessions were performed with a range of 1-4 RFA sessions per patient. RFA was technically successful in all RFA sessions (100%). There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 hours) and short-term follow up (4 week). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging after RFA treatment was available in 8/10 patients. Tumor progression was noted in 2 patients, whereas tumor regression was noted in 6 patients (>50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93 to 42.2 months). Currently, 2 patients remain alive at 53 and 73 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy. Conclusion: In our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard of care chemotherapy. In this select cohort, median survival (20.5 months) was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC.

Period Analysis of Intraracial Differences in Incidence and Survival Rates in Epithelial Ovarian Cancer

Background. To explain the difference in the incidence and relative survival in a population-based cohort of women with epithelial ovarian cancer (EOC) postdiagnosis in the last forty years. EOC is the most common type of all ovarian cancers, but there is inadequate information about the variations related to long-term EOC survival. Methods. We acquired the incidence and relative survival rate data from the Surveillance, Epidemiology, and End Results (SEER) registries to analyze the epidemiological variations from 1974 to 2013 in EOC-affected individuals. The survival disparities in EOC-specific individuals due to age, race, and socioeconomic status (SES) were performed by Kaplan-Meier analysis. The Results. The overall incidence of EOC progressively declined to 9.0 per 100,000 from 11.4 in the last forty years. The median survival rate improved to 48 months in the first decade from a previous of 27 months in the fourth decade. The 5-year relative survival rate (RSR) increased to 44.3% that was previously 32.3% at the same time. However, between whites and blacks, an increase from 11 to 18 months was observed in the median survival differences. Between the low and high poverty groups, it was increased from 7 months to 12 months, respectively. Conclusions. The incidence rate of RSR and EOC-specific individuals in the last forty years was improved. However, the survival rates among different races and SES differed over time.

Clinician estimates of prognosis: accuracy and impact—a retrospective inpatient hospice study

ObjectiveTo evaluate the accuracy and impact of clinicians’ estimates of prognosis (CEP) in patients referred for hospice inpatient care.MethodsRetrospective review of 12 months’ referrals to a London hospice unit. Data extracted included date of referral, admission and death and CEP.ResultsN=383. Mean age 72 years (range 24–101). CEP accuracy: Median survival where CEP was ‘days’ (n=141) was 7 days (0–164); CEP ‘weeks’ (n=167) was 14 days (1–538); CEP ‘months’ (n=75) was 32 days (2–507). Kaplan-Meier survival curves showed significant difference between CEP of ‘months’ and ‘weeks’ (p<0.0001); ‘months’ and ‘days’ (p<0.0001); but not ‘days’ and ‘weeks’ (p=0.1). CEP impact: admission waiting time increased with increasing CEP: CEP ‘days’ (n=105) median 1 day (0–14); CEP ‘weeks’ (n=154) median 2 days (0–46); CEP ‘months’ (n=69) median 3 days (0–46). No significant difference was demonstrated in the number of discharge planning conversations between groups (0.9/patient).ConclusionsCEP was accurate in over half of the cases but did not adequately discriminate between those with prognoses of days or weeks. CEP may affect the prioritisation given to patients by hospices. Inaccurate CEP on referral forms may influence other aspects of care; however, further research is needed.

MPC-2 Clinical course and prognosis of lower-grade glioma, IDH wildtype and pTERT mutant

Background and Purpose: In the cIMPACT-Now update 3, it was proposed that grade 2 astrocytic gliomas without IDH-mutations and grade 3 astrocytic gliomas with TERT promoter mutations should be designated as diffuse IDH wildtype astrocytic glioma with molecular features of WHO grade IV glioblastoma. Therefore, we investigated whether this group of tumors actually corresponds to grade IV prognostically in cases that we encountered ourselves. Cases and Methods: Among the 65 patients having primary astrocytic glioma who were operated in our hospital from January 2016 to March 2021, the prognostic values of seven patients with lower-grade glioma, IDH wildtype, and pTERT mutant were investigated. Results: Among the seven patients, the median age was 59 years (50–66 years). Four of them had anaplastic astrocytoma, two had diffuse astrocytoma, and no tumor lesion could be identified upon histological examination for one patient. The male-to-female ratio was 1:6. MGMT methylation was observed in two patients (29%). The median survival was 20 months, with a significantly worse prognosis when compared with lower-grade glioma without the TERT promoter mutation (13 patients: median survival 40 months), but a better prognosis when compared with glioblastoma (45 patients: median survival 13 months) (Log-rank p = 0.0051). Conclusion: Although EGFR amplification, combined whole chromosome 7 gain, and whole chromosome 10 loss were not examined, the prognostic value of lower-grade glioma, IDH wildtype, and pTERT mutant was not as poor as that of glioblastoma. Further investigation is required to confirm whether these groups of tumors should be treated in the same way as grade IV glioblastoma.

ET-8 Integrated diagnostic approach to predict prognosis for malignant gliomas

Previous studies indicated that MGMT promoter methylation status with IDH and TERT promotor mutation are major prognostic factors in glioma. In addition to these molecular features, we have been assessing drug sensitivity against several chemotherapeutic agents, including temozolomide (TMZ). Here, we examined if this combined information could strongly predict drug sensitivity and the prognosis in glioma patients. One hundred and twenty-five IDH wild-type gliomas (WHO grade III and grade IV) were included in this study and retrospectively analyzed. Among them, we focused on 37 patients with partial surgical resection and biopsy to assess radiological difference on MRI. The primary cultured tumor cells were exposed with several compounds for 72 hours, then ATP based cell viability assay was performed. The favorable radiological therapeutic effect was found in 6 out of 8 (75%) with MGMT promoter methylated cases, while unfavorable in 23 of 29 (79.3%) with MGMT promoter unmethylated cases (p=0.008). The drug screening assay demonstrated that 7 of 10 cases with favorable TMZ sensitivity in vitro showed response on MRI, whereas 22 of 27 (81.5%) cases with TMZ resistance in vitro indicated tumor progression (p=0.006). Of note, all 5 cases with sensitive to TMZ and methylated MGMT promoter demonstrated favorable radiological response (p=0.002). These 5 cases tended to survive longer (median survival time, 697 days) as compared to others (median survival time, 391 days, p=0.13). These data indicate that integrated approach with genomic assessment and drug screening test may predict therapeutic response to chemotherapy and contribute selecting optimal therapy in glioma patients.