The Surgical Management of Peptic Ulcer Disease

The treatment of peptic ulcer disease has evolved substantially through the decades since the discovery of acid-reducing agents and helicobacter pylori bacteria. With the success of medical treatment, surgical therapy continues to play a less prominent role in the care of this disease. Operative candidates include the naive patient treated with over-the-counter NSAIDs who are often those with undiagnosed Helicobacter pylori, requiring less complicated initial surgery. With more surgeons graduating with less experience operating on PUD with evolving operative techniques, the question arises as to what constitutes the optimal surgical approach, especially in the elective vs. emergent settings. Recent literature discussing GI bleeding associated with COVID-19 also merits discussion of surgical options in this chapter. Future surgical options may include minimally invasive endoscopic surgeries akin to per-oral endoscopic myotomy of the pylorus; however, this has not yet been described in this disease.

Patient-derived organoids as a platform for modeling a patient’s response to chemoradiotherapy in esophageal cancer

Abstract3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes. Endoscopic biopsies of treatment-naive patients at a single tertiary care center were used to generate esophageal cancer PDOs, which were treated with standard-of-care chemotherapy, gamma-irradiation, and newer non-standard approaches, such as proton beam therapy or two small molecule inhibitors. Clinical outcomes of patients following neoadjuvant treatment were compared to their in vitro PDO responses, demonstrating the PDO’s ability to mirror clinical response, suggesting the value of PDOs in prediction of clinical response to new therapeutic approaches. Future prospective clinical trials should test the use of pre-treatment PDOs to identify specific, targeted therapies for individual patients with esophageal adenocarcinoma.

SP7.1.8 Routine use of opioids for post-operative pain in opioid naïve patient can risk long term dependence

Aims and Objectives Aim of our study was to evaluate the current practices of prescribing opioids for post-operative pain in opioid-naive patients in our region and the risk of prolonged opioid use among them. Methods A retrospective cohort study was performed where cohort consisted of patients who had surgery in 2018 with at least one year follow up. Endpoints were the proportion of all patients and opioid naïve patients, discharged on opioid prescription and proportion of opioid naïve patients who developed opioid dependence after one year. Results During 2018, 17524 patients underwent a total of 20526 surgical procedures by pan surgical specialties in our hospitals. 8772 patients (50%) were discharged with opioid prescription. 673 (7.70%) of those required further opiate prescriptions after discharge, of those requiring opiates, 331 had no opiate exposure before surgery (342 had previous opiate exposure). In opioid naïve patients, at 1 year follow up 151 (45%) had no further opiate prescriptions, but 180 (55%) required ongoing opiate prescriptions after one year follow up. The risk of opioid dependence after surgery is significant in opioid naïve patients. Conclusion Results are alarming and evidence-based strategies, national and local guidelines are needed to prevent the opioid crisis in the UK. There is a need for a national campaign to minimize the dependence on opioids and to find, better alternatives to opioids.

Retrospective, observational study on usage of evogliptin in T2DM patients: A real-World experience in Indian patients

This study aimed to assess effectiveness and safety of Evogliptin 5 mg in patients with T2DM who were prescribed Evogliptin alone or with other oral hypoglycemic agents in real world scenario. Overall 20 patients who received Evogliptin as routine clinical practice in management of T2DM were analyzed retrospectively from single center. Data collected from past medical records. Primary endpoint was mean changes in HbA1c from baseline to weeks 24 and secondary endpoints were Change in HbA1c from baseline to weeks 12 Change from baseline in FPG & PPG at weeks 12 & 24.Significant reduction in HbA1c at the end of 12 and 24 weeks of Evogliptin therapy was - 0.9% and -1.45% respectively from the baseline of HbA1c 8.6% (p value <0.001). At the end of 12 and 24 weeks of addition of Evogliptin, significant reduction in FBG were seen i.e -49.5 mg/dl and -90.7mg/dl respectively from base line of 182 mg/dl and reduction in PPG was -79.4mg/dl and -116.6mg/dl respectively from base line 277 mg/dl (p value <0.001). Evogliptin was found to be effective when added to the patients who were uncontrolled on dual / triple oral anti-diabetic medications and even in treatment naïve patient. It effectively showed reduction in HbA1c, FBG and PPG and the end of 12 and 24 weeks when added to existing anti-diabetic medications & well tolerated in type 2 diabetes Indian patients.Small sample size and retrospective study

Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes

Objectives DRAKO (NCT02850263) is a 24-month, prospective, non-interventional, multi-centre cohort study which enroled patients diagnosed with centre-involving diabetic macular oedema (DMO). The study aims to evaluate standard of care with intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the anti-vascular endothelial growth factor (anti-VEGF) treatment-naive patient cohort after 12-month follow-up. Methods Study eyes were treated with IVT-AFL as per local standard of care. The mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline at 12 months were measured and stratified by baseline factors. The number of injections and safety data were also evaluated. Results A total of 507 patients were enroled from 35 centres. Mean (SD) baseline BCVA was 71.4 (12.0) letters and CST was 448.7 (88.7) µm, with 63.1% of patients presenting with baseline BCVA ≥ 70 letters (mean 78.1). Mean (SD) change in BCVA of 2.5 (12.2) letters and CST of −119.1 (116.4) µm was observed at month 12. A 7.3 letter gain was observed in patients with baseline BCVA < 70 letters. Mean number (SD) of injections in year one was 6.4 (2.1). No significant adverse events were recorded. Conclusion Year one results indicated that IVT-AFL was an effective treatment for DMO in standard of care UK clinical practice, maintaining or improving visual acuity in treatment-naive patients with good baseline visual acuity, despite some patients being undertreated versus the summary of product characteristics. These results also demonstrated the clinical importance and meaningful impact of diabetic retinopathy screening in the UK.

Uni-, Bi- or Trifocal Hepatocellular Carcinoma in Western Patients: Recurrence and Survival after Percutaneous Thermal Ablation

Multifocality is usually reported as a pejorative factor after percutaneous thermal ablation (PTA) of HCC but little is known in Western series. Recurrence and survival were extracted from a prospective database of all patients who underwent PTA for ≤3 cm HCC. From January 2015 to April 2020, we analyzed 281 patients with unifocal (n = 216), bifocal (n = 46) and trifocal (n = 16) HCC. PTA of bi- and trifocal HCC resulted in a high risk of very early (<6 months) distant recurrence (38.8% and 50%, respectively). Median RFS was 23.3 months (95% CI:18.6–30.4), 7.7 months (95% CI:5.1–11.43, p = 0.002) and 5.2 months (95% CI:3–12.3, p = 0.015), respectively, for uni-, bi- and trifocal HCC groups. In a multivariate analysis, both bifocal (HR = 2.46, p < 0.001) and trifocal (HR = 2.70, p = 0.021) vs. unifocal HCC independently predicted shorter RFS. Median OS in trifocal HCC group was 30.3 months (95 CI:19.3-not reached). Trifocal vs. unifocal HCC independently predicted shorter OS (HR = 3.30, p = 0.008), whereas bifocal vs. unifocal HCC did not (p = 0.27). Naïve patient (HR = 0.42, p = 0.007), AFP > 100 ng/mL (HR = 3.03, p = 0.008), MELD > 9 (HR = 2.84, p = 0.001) and steatotic HCC (HR = 0.12, p = 0.038) were also independent predictors of OS. In conclusion, multifocal HCCs in a Western population have a dramatically increased risk of distant recurrence. OS after PTA of trifocal HCC is significantly below what was expected after a curative treatment.

Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer.

2511 Background: CD73 is implicated in tumor resistance to checkpoint immunotherapy (CPI) and plays a critical role in adenosine-mediated immune suppression. Uliledlimab, a differentiated CD73 antibody, inhibits the adenosine pathway in a non-competitive and unique intra-dimer binding mode. Uliledlimab suppresses tumor growth when combined with a PD-(L)1 inhibitor in multiple pre-clinical models. Methods: This 3+3 dose-escalation phase 1 study (NCT03835949) evaluated safety, tolerability, PK, PD and preliminary efficacy in cancer patients. Uliledlimab was administered intravenously at doses of 5, 10 or 15 mg/kg weekly (QW) or 15 or 20 mg/kg every 3 weeks (Q3W) alone in the first cycle and in combination with atezolizumab (1,200 mg Q3W) starting on week 4. Soluble CD73 in serum and CD73 receptor occupancy (RO) in circulating CD19+ B cells were measured. Expression of PD-L1, CD73 and A2A receptor was analyzed in baseline tumor specimens (n = 14). Tumor responses were assessed by RECIST/iRECIST. Results: As of 17 January 2021, 20 patients with advanced solid tumors were enrolled (M:F 8:12; mean age = 64; median prior regimens = 3 (range 1-9)). Uliledlimab was well-tolerated with no dose limiting toxicity. The most common treatment-related adverse events were first dose infusion related reactions (65%, n = 13) most commonly comprising chills/rigors, nausea, and vomiting (Grade 1 or 2) that resolved in subsequent infusions. PK appears linear at doses ≥ 10 mg/kg and modelling indicated a mean derived effective half-life of ̃19 days. Soluble CD73 was undetectable and complete RO was achieved in all patients after the first dose at ≥ 10 mg/kg. Anti-drug antibody was detected in 3/20 patients (15%). Among 13 efficacy-evaluable patients dosed at ≥ 10 mg/kg, complete response (CR = 1) and partial response (PR = 2) were observed in 3 patients (ORR = 23%) together with 3 stable disease (SD) patients (DCR = 46%). One PD-(L)1 inhibitor naïve patient with clear cell ovarian cancer achieved CR at 10 mg/kg QW and remains on study after 12 months. Two patients with NSCLC dosed at 15 mg/kg QW and 20 mg/kg Q3W, respectively, achieved PR. One patient failed nivolumab and the other received no prior PD-(L)1 inhibitor treatment. CD73 was expressed on 78% (mean) of malignant cells from archival tumor specimens in responders compared to 23% in non-responders. Conclusions: Uliledlimab is safe and well tolerated up to 20 mg/kg Q3W and 15 mg/kg QW. Full saturation of circulating and cell-bound CD73 was achieved at doses ≥ 10 mg/kg. Uliledlimab exhibited evidence of clinical activity in both PD-(L)1 treatment naïve and refractory cancer patients with high archival tumor expression of CD73. The results of this phase 1 study encourage further clinical investigation to evaluate the efficacy of uliledlimab in the treatment of solid tumors. Clinical trial information: NCT03835949.

Methylphenidate-induced psychosis in a young antipsychotic-naïve female patient

Methylphenidate (MPD) is commonly prescribed for patients with Attention Deficit/Hyperactivity Disorder (ADHD). Although used off-label, MPD forms part of complex and multifactorial treatment regimen for narcolepsy and hypersomnia, together with including behavioural interventions. The drug is sometimes also prescribed off-label to subjects with other mental illness or somatic condition to improve intellectual outcome, ease fatigue or enhance the ability to concentrate. Common side effects include headache, insomnia, decreased appetite and hypertension. Concurrently, clinicians should be aware of relatively rare but potentially threatening adverse effects including agitation and psychotic symptoms. Several case reports regarding MPD-induced psychosis have been published, but most of them regard children or teenagers (1) and much less is known about drug-induced psychosis in adults (2). In this article, we present a case report of MPD-induced psychosis in a 31-year-old, antipsychotic-naïve patient. Careful evaluation including clinical examination, medical and family history and possible early signs of psychosis is recommended each time before MPD treatment will be initiated.

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy–naïve patient: a case report

Background Enzalutamide is an orally administered drug that blocks signaling in the androgen receptor with clinical activity in both chemotherapy–naive and post-chemotherapy patients with castrate-resistant prostate cancer (CRPC). Enzalutamide is generally well-tolerated, but dose reductions are nonetheless needed in case of side effects. Case An 82-year-old patient with chemotherapy–naive metastatic castration-resistant prostate cancer was treated with a very low dose of 40 mg enzalutamide once daily. The trough levels of enzalutamide and the active metabolite N-desmethylenzalutamide were 4.5 mg/L and 3.0 mg/L, respectively. This exposure provided a long-term response without any significant side effects. Conclusion Low doses of enzalutamide may be efficacious, while also reducing the risk of side effects. Furthermore, employing a lower dose would reduce healthcare costs and increase access to enzalutamide. Studies exploring the efficacy of lower enzalutamide doses are warranted.