Safety and Efficacy of Endoscopic Full Thickness Resection of Upper Gastrointestinal Lesions Using a Full Thickness Resection Device: A Systematic Review and Meta-analysis.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) is a promising technique that allows for a minimally invasive resection of mucosal and submucosal lesions in the gastrointestinal (GI) tract. The data regarding the efficacy and safety of performing EFTR of upper GI lesions using a full-thickness resection device (FTRD) is limited. Hence, we performed a systematic review and meta-analysis of the studies that evaluated this technique. METHODS: We performed a comprehensive systematic search of multiple electronic databases and conference proceedings that reported outcomes of EFTR using the FTRD system. The weighted pooled rates of technical success, complete (R0) resection, adverse events (AE), and residual or recurrent lesions were analyzed with 95% CI using the random effects model. RESULTS: Eight studies with a total of 139 patients who underwent EFTR of upper GI lesions were included in the study. The pooled, weighted rate of technical success was 88.2% (95% CI: 81.4-92.7%, I2 : 0). The R0 resection rate was 70.7% (95% CI: 62.5-77.8%, I2 : 0). Overall AE rates were 22.1% (95% CI: 15.8-30.1%, I2 : 0), however, most of the AEs were minor. Of the patients who had follow-up endoscopies, the residual and/or recurrent lesion rate was 6.1% (95% CI: 2.4-14.4%, I2 : 0). Heterogeneity in the analysis was low. CONCLUSIONS: EFTR using the FTRD seems to be effective and safe with acceptable R0 resection rates and low recurrence rates. Further prospective studies are required to validate our results and to compare various modalities of endoscopic resection with this single-step EFTR device.

Diagnostic accuracy of EUS-guided fine-needle biopsy sampling by macroscopic on-site evaluation: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Assessment of EUS-guided fine-needle tissue acquisition by macroscopic on-site evaluation (MOSE) is gathering attention. Studies report good diagnostic parameters with MOSE; however, the overall data are limited. We conducted this systematic review and meta-analysis to report on the pooled diagnostic assessment parameters of EUS-guided tissue acquisition by MOSE using fine-needle biopsy sampling (FNB). METHODS: Multiple databases were searched (from inception to December 2021), and studies that reported on the diagnostic assessment of EUS-guided tissue acquisition by MOSE were selected. Pooled diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were calculated by standard meta-analysis methods following the random-effects model. Heterogeneity was assessed by I2 statistics. RESULTS: Fourteen studies were included in the analysis, and 1508 lesions were biopsy sampled in 1489 patients undergoing EUS-guided tissue acquisition. MOSE definition included a visible core of tissue with opacity and "wormlike" features of adequate size and length (≥4 mm). The pooled accuracy of FNA and/or FNB specimens in yielding a pathologic diagnosis by MOSE was 91.3% (95% confidence interval [CI], 88.6-93.3; I2 = 66%), pooled sensitivity was 91.5% (95% CI, 88.6-93.6; I2 = 66%), pooled specificity was 98.9% (95% CI, 96.6-99.7; I2 = 80%), pooled positive predictive value was 98.8% (95% CI, 97.4-99.5; I2 = 33%), and pooled negative predictive value was 55.5% (95% CI, 46.9-63.9; I2 = 95%). Subgroup analyses by newer-generation FNB needles demonstrated similar pooled rates, with minimal adverse events (2.5%; 95% CI, 1.5-3.9; I2 = 21%). CONCLUSIONS: Excellent pooled diagnostic accuracy parameters were demonstrated in EUS-guided tissue acquisition by FNB using the MOSE method.

Real-world use of first-generation antiandrogens: impact on patient outcomes and subsequent therapies in metastatic castration-resistant prostate cancer.

OBJECTIVES: To investigate the recent real-world use of first-generation antiandrogens (FGAs) in metastatic castration-resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study. PATIENTS AND METHODS: The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan-Meier method and groups compared using log-rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model. RESULTS: We identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow-up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre-treatment prostate-specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life-prolonging treatments for mCRPC or their PSA50 response rates. CONCLUSION: In our present cohort, FGAs were commonly used in lower-risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS.

Surgical management of breast cancer in Victoria: A state-wide audit.

AIM: The Victorian Tumour Summits are an initiative of the Victorian Integrated Cancer Services to engage clinicians and consumers in identifying unwarranted variations in cancer care across the state. From the analysis presented at the Victorian Breast Tumour Summit in 2021, this study provides a state-wide overview of epidemiology and surgical care of breast cancer in Victoria to outline any variations in care across the state, and limitations in data reporting, which impacts the understanding of breast cancer burden and service planning. METHODS: A retrospective analysis of Victorian breast cancer patients diagnosed between 2016 and 2018 was performed using a linked data set provided by the Department of Health. The linked data sources include Victorian Cancer Registry, Victorian Admitted Episodes Dataset and Victorian Radiotherapy Minimum Data Set, from which patient demographic details, tumor characteristics and treatment records were extracted. Pearson's chi-squared test was used to determine the statistical significance of relationships between various categorical parameters. Variables including demographics, types of surgery (breast-conserving vs. mastectomy), rates of neoadjuvant chemotherapy, and time to surgery were examined. RESULTS: One thousand nine hundred thirty-seven patients with ductal carcinoma in situ and 13,375 patients with invasive breast cancer (IBC) were included. Of 11,351 patients with stages I-III IBC (85%, N = 13,375) 66% underwent breast-conserving surgery (BCS), and 31% underwent mastectomy. The ratio of mastectomy to BCS increased with increasing disease stage. Neoadjuvant chemotherapy was utilized in 11% of early IBC patients who were surgically treated. Eighty-three percent of patients undergoing upfront breast surgery were treated within 5 weeks of diagnosis, with a significant difference in the median time to surgery between public and private sectors. Breast reconstruction was performed in 37% of mastectomy patients, of whom 83% underwent immediate breast reconstruction, and 17% underwent delayed breast reconstruction. CONCLUSIONS: Victorian breast cancer data show a high quality of surgical care coordination. Significant gaps in our data warrant future improvements in the Victorian breast cancer notification system and access to pharmaceutical data for an enhanced understanding of the breast cancer treatment pathways and care delivery.

Treatment outcomes for patients with metastatic castrate-resistant prostate cancer following docetaxel for hormone-sensitive disease.

AIM: Optimal treatment for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D-ADT). This study sought to define the therapy used and associated activity following D-ADT. METHODS: Retrospective analysis of patients with mHSPC treated with one or more cycles of D-ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first-line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate-specific antigen (PSA) reduction >50% and time from 1L to second-line (2L) treatment initiation. RESULTS: A total of 93 patients received D-ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9-16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9-7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second-line treatment was 7.3 months (1.3-27.4), which did not differ significantly between treatment groups. CONCLUSIONS: Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D-ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D-ADT needed.

Pembrolizumab-Induced Immune-Mediated Hepatitis and Concurrent Hepatitis B Reactivation in a Patient With Non-Small Cell Lung Cancer.

New immuno-therapeutic agents like pembrolizumab used in cancer treatment are known to cause immune-mediated hepatitis. Most of these cases are straightforward when the onset of transaminitis correlates with the introduction of the medication. This agent causing hepatitis B reactivation has been reported only once. To have both these adverse effects occurring at the same time in a patient is uncommon and presents a clinical challenge. Our patient was a 49-year-old gentleman diagnosed with metastatic adenocarcinoma of the lung seven months ago. He was started on pembrolizumab, as the malignant tissue obtained during biopsy had high program death-ligand 1 (PDL1) expression. On reviewing the labs ordered during the time of cancer diagnosis, this man has evidence of chronic hepatitis B with positive hepatitis B surface antigen and positive hepatitis B core immunoglobulin G (IgG) antibody. He presented with acute hepatitis, and workup showed features of hepatitis B reactivation, but the extent of reactivation was not adequate to explain the presentation, hence investigations were pursued. This led the way to the diagnosis of a combined hepatitis B reactivation and drug-induced immune hepatitis in this case. He responded promptly to the withdrawal of the agent and steroids. On follow-up, his liver function panel had significantly improved.  This case is very unique in two aspects. First, to our knowledge, there is only one case reported of pembrolizumab-induced hepatitis B reactivation. In addition, our patient also had immune-mediated hepatitis induced by pembrolizumab. It is very rare to have a combination of these two presentations to be seen in a patient at the same time. Pembrolizumab-induced immune hepatitis can coexist with hepatitis B reactivation following therapy with this agent.

Carcinoma of the esophagus in Tamil Nadu (South India): 16-year trends from a tertiary center.

BACKGROUND: In the Western world, esophageal adenocarcinoma has surpassed in incidence squamous cell carcinoma. AIM: To determine the trend changes in histology and site distribution of esophageal malignancy between 1989 and 2004 in a southern state of the Indian subcontinent. METHOD: A retrospective study on 994 patient records with esophageal carcinoma esophagus. Age, gender, clinical presentation and duration of illness were recorded in a prestructured proforma. The site of the tumor was classified as upper, mid, lower esophagus and esophagogastric junction. The 16 year study period was divided into four equal cohorts. Statistical analysis was performed using the chi-square test and the one way ANOVA wherever appropriate; p < 0.05 was considered significant. RESULTS: Squamous cell carcinoma was the most common malignancy, seen in 912 (92%) patients. 82 patients (8%) had adenocarcinoma. 65 of these 82 patients (79%) had an esogastric junction malignancy and 17 (21%) a tumor in the distal third of the esophagus. No time trends were discernible with regard to the clinical presentation, frequency, mean age or gender. However, an increase in the number of patients below the age of 40 was noted (p=0.008). In squamous cell carcinoma of the esophagus, there was an overall increase in the mean age of occurrence (p=0.05), but no significant changes in the gender ratio. The lower esophageal cancers outnumbered the midesophageal cancers in the 4th cohort and the former represent the most common site of malignancy. CONCLUSION: Squamous cell carcinoma is the most common type of esophageal cancer in the Indian subcontinent, located with a predilection in the distal third. Adenocarcinoma is uncommon and affects more frequently men younger than 40.

Stomach carcinoma in the Indian subcontinent: a 16-year trend.

BACKGROUND: Gastric malignancy is one of the most common causes for cancer-related deaths. Reports from the west have shown a paradigm shift in the site of occurrence with malignancies of the gastric cardium increasing in frequency, reports which are contrary to information from the Middle East and South Asia. AIM: To determine trend changes in distribution of gastric malignancy between 1989 and 2004 in the southern state of Tamil Nadu in India. MATERIALS AND METHODS: The study period was divided into four cohorts of four years each (1989-1992, 1993-1996, 1997-2000 and 2001-2004) for the analysis of the changes in trend for subsite specificity, age and gender predilection. RESULTS: Clinically, there were no significant differences in the presenting symptoms or physical signs in the four cohorts. The antrum was the most common site of predilection, no site-specific change was noted and males continued to be more commonly affected of the two sexes. Gastric cancer was significantly higher above the age of 40 years in all the four subsites and cohorts. A decrease in the mean age was observed for men with cancers of the esophagogastric junction (OGJ) (P < 0.0001) and the proximal stomach (P < 0.0001), while junctional malignancy (P < 0.0001), cancers of the proximal stomach (P < 0.0001) and the antrum (P = 0.03) tended to occur progressively later among women. CONCLUSION: No change in site specificity or gender predilection for gastric adenocarcinoma has been noted in the past 16 years. However, a gender-dependent paradigm shift in the mean age of presentation is discernible for cancers involving the OGJ, proximal stomach and antrum.