May-June 2018

Synopsis: Prognosis after curative-intent resection of node-negative, ER-positive, HER2-negative breast cancer is favorable, and certain low risk patients receiving hormonal therapy may not benefit from the addition of adjuvant chemotherapy. The 21-gene recurrence-score assay (Oncotype DX) predicts benefit from chemotherapy for women with high 21-gene RS (>26) and identifies those patients with low scores (<11) where there is no marginal benefit to adding chemotherapy to endocrine treatment. The Trial Assigning Individualized Options for Treatment (TAILORx) was a multicenter RCT evaluating the role of chemotherapy for 6,711 patients in the midrange of the Oncotype Dx (defined by scores 11-25). The 9-year rate of distant recurrence was approximately 5% and did not vary by chemotherapy use. By exploratory analysis, there were significant interactions between chemotherapy treatment and age, such that women over 50 years did not benefit from additional chemotherapy but younger women with a score of 15 or greater evidenced a significant long-term benefit with chemotherapy. Thus, the authors conclude that chemotherapy can be omitted in node-negative, ER-positive, HER2-negative breast cancer patients receiving hormonal therapy if (1) age >50 and recurrence score <25, or (2) age <50 and recurrence score <15 – which together spares up to 85% of women with early breast cancer from adjuvant chemotherapy. The trial excluded node-positive patients and those with small (<0.5 or <1 cm) tumors, where further data is still needed.

Synopsis: Nearly 40% of children with appendicitis have already perforated, which is associated with higher costs, longer hospitalizations, and higher hospital readmission and complication rates. The authors sought to determine whether there was an association between increased health care utilization (defined as the number of primary care health encounters 1 to 12 months prior to presentation) and lower rates of perforated appendicitis in children. Health care utilization may reflect patient attitudes toward health care, health literacy, socioeconomic status, and coverage patterns. Using a large administrative national private insurance database, they identified over 19,000 children who had appendicitis in the 4 year study period (2010-2013) that met inclusion criteria. In the adjusted model, outpatient health care utilization before presentation was associated with lower odds of perforated appendicitis (OR 0.63; CI [0.58-0.69]; p<0.001). This association increased with visit frequency in the year before presentation. The authors concluded that primary health care relationships may facilitate timely presentation or serve as a marker for health-related self-efficacy, thereby contributing to outcomes for acute surgical conditions. Results should be interpreted with caution, however, as use of a private insurance database may limit generalizability.

Synopsis: Catecholamine vasopressors (ex. norepinephrine, epinephrine, dopamine and dobutamine) are the most common first-line medication used in distributive shock prescribed, but have important complications, including risk of atrial fibrillation and arrhythmias. Vasopressin is a non-catecholaminergic vasopressor that may decrease risk of arrhythmia due to decreased catecholamine receptor stimulation. This systematic review pooled data from 13 studies (N=1462 patients) to assess the incidence of atrial fibrillation in patients with distributive shock. The majority of studies included enrolled patients with septic shock, but several studies that enrolled patients with vasoplegia after cardiac surgery were included . In the pooled analysis, there was a significant reduction in the risk of atrial fibrillation associated with administration of vasopressin (RR, 0.77 [95% CI, 0.67-0.88]). Importantly, the majority of this result (74.8% weight) was driven by results of a single-center study in post-cardiac surgery patients. When patients with septic shock and post-cardiac surgery vasoplegia were considered separately, there was a significant difference for post-cardiac surgery patients (RR, 0.77 [95% CI, 0.67-0.88]) but there was not a significant difference in patients with septic shock (RR, 0.76 [95% CI, 0.55-1.05]). A variety of secondary outcomes were also assessed, including 30-day mortality, need for renal replacement therapy, length of stay, stroke and digital ischemia. The results of these secondary analyses were inconclusive, primarily owing to differences in level of bias within individual studies and wide confidence intervals within the pooled analyses. In summary, in this systematic review and meta-analysis, patients with distributive shock had a lower risk of atrial fibrillation if treated with a combination of vasopressin plus catecholamine vasopressors compared to catecholamine vasopressors alone. However, in this study, the significance was primarily driven by the population of post-cardiac surgery patients. Further studies are needed to more clearly define additional benefits in patients with sepsis and on other clinically relevant outcomes, such as mortality and need for renal replacement therapy. 

Synopsis: Appendix adenocarcinomas have an incidence of 0.12/1,000,000 and can demonstrate mucinous and signet ring cell features. Compared to low-grade appendiceal mucinous neoplasms (LAMNs), appendix adenocarcinomas are more aggressive and can metastasize systemically in up to 20% of cases. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for patients with appendiceal adenocarcinoma with peritoneal metastasis. Peritoneal cancer index (PCI) measures the distribution of disease and ranges from 0-39 whereas the completeness of cytoreduction (CC) score measures the completeness of clearance achieved. Both PCI and CC scores are prognostic indicators for outcomes in appendiceal adenocarcinoma. Between 2005 and 2015 at a national peritoneal tumor center in the UK, 65 patients out of 574 underwent HIPEC/CRS for appendicaeal adenocarcinoma. The 5 year overall survival (OS) was 55.5%. A PCI <7 at surgery had a higher OS compared with PCI ≥7 (5yr OS 83% VS. 30%, P<0.005). CC of 0 was associated with significantly higher OS compared with CC 1-3 patients (5yr OS 70% VS. 20.4%, P<0.005). Preoperative CEA <6 had significantly higher OS than those with CEA ≥6 (5yr OS 63.1% VS. 14.1%, P<0.005). Patients with signet ring cells showed a trend towards poorer survival but not statistically significant. Disease event-free survival (DeFS) represents recurrence free survival in CC0 patients and progression free survival in CC1-3 patients. The 5-year DeFS was 36.1%. PCI <7 was associated with significantly higher DeFS compared with PCI ≥7 (5yr DeFS 60.4% VS. 13.3%, P<0.005). CC0 cytoreduction had a significantly higher DeFS than CC1-3 (5yr DeFS 45.3% VS. 15.8%, P=0.014). Preoperative CEA <6 had a significantly higher DeFS than those with a CEA ≥6 (5yr DeFS 43% VS. 11.3%, P<0.005). Patients with N0/Nx had statistically higher OS and DeFS than N1 patients. “Complete cytoreduction” for pseudomyxoma peritonei caused by LAMN is considered CC0 and CC1 because in theory the HIPEC can penetrate to a depth of 3mm. This study suggests that CC0 patients do significantly better than CC1 patients and highlights the importance of CC0 cytoreduction. ***CC0 = no residual disease; CC1 = nodules < 2.5mm remaining; CC2 = nodules between 2.5mm and 2.5cm remaining; CC3 = nodules >2.5cm remaining.