Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.     

Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Acute coronary syndrome following arteriovenous fistula creation in a post CABG patient: A steal phenomenon from coronary artery to subclavian artery

A 70‐year‐old man with a history of coronary artery bypass grafting 15 years back and arteriovenous (AV) fistula creation in the left arm 1 month back presented with acute coronary syndrome (ACS). He had not received dialysis before his referral. We felt the most likely etiology for these complaints was increased cardiac oxygen demand from an increased cardiac output related to the newly formed left AV fistula. Coronary angiography was done to detect any significant stenosis in the native or grafted vessels. This revealed that the left subclavian artery was totally occluded in the ostioproximal segment and the coronary arteries did not have occlusions to explain the ACS setting. CT angiography confirmed the angiographic findings of the totally occluded left subclavian artery followed by a well‐developed and patent left internal mammary artery to left anterior descending artery. This led to the consideration of a steal syndrome from the coronary artery by the subclavian artery distal to the occlusion. A successful percutaneous endovascular intervention on the left subclavian artery occlusion was performed. Subsequently, the patient became asymptomatic and experienced a dramatic increase in left ventricular ejection fraction.     

The impact of cytogenetic risk on the outcomes of allogeneic hematopoietic cell transplantation in patients with relapsed/refractory acute myeloid leukemia: On behalf of the acute leukemia working party (ALWP) of the European group for blood and marrow transplantation (EBMT)

Karyotypic analysis at time of diagnosis has an important value in determining initial response to treatment, remission duration and overall survival (OS) in acute myeloid leukemia (AML). Less is known about its value before allogeneic hematopoietic cell transplantation (allo‐HCT) in patients transplanted with active disease, either relapsed or primary refractory (Rel‐Ref) AML. We explored the impact of cytogenetic risk (stratification according to MRC‐UK) in 2089 patients with either Ref (n = 972) or Rel AML (n = 1117) transplanted during the period 2000‐2017. Overall, 154 patients had a favorable risk, 1283 had an intermediate risk and 652 had an adverse cytogenetic risk. Median follow‐up was 49 months. Compared to the favorable risk group, intermediate and adverse risk patients were associated with worse leukemia‐free survival and OS and also with a higher incidence of relapse. In a subgroup analysis of patients in the intermediate risk group harboring Fms‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD), this remained an important prognostic factor, being associated with worse outcomes. When analyzing patients according to the intensity of the conditioning regimen, no differences were observed for the main transplant outcomes. In conclusion, in patients diagnosed with AML and transplanted with active disease, karyotype remains an important prognostic factor, allowing splitting patients into different risk groups according to their cytogenetics. Similarly, FLT3‐ITD mutation also remains a negative prognostic factor in this population.     

Relation Between Tumor Size and Lymph Node Metastasis According to Subtypes of Breast Cancer

PurposeTumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS).MethodsWe retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm]).ResultsThis study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes (p = 0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097–1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013–1.086; p = 0.007), HER2 (HR, 1.069; 95% CI, 1.014–1.126; p = 0.013), and TNBC (HR, 1.038; 95% CI, 1.01–1.067; p = 0.008).ConclusionThe incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes.