Opioid prescribing after breast surgery: A systematic review of guidelines.

BACKGROUND: Despite advances in opioid-sparing analgesia, opioid prescribing in breast surgery remains suboptimal. Besides delayed rehabilitation, excess post-operative opioids may contribute significantly to opioid dependence. This systematic review of guidelines evaluates current opioid-prescribing recommendations after breast surgery to identify trends in prescribing. Additionally, it compares recommendations on different non-opioid and non-pharmacological adjuncts. METHODS: Electronic databases were searched systematically using terms "breast surgery", "analgesia", "opioid" and "guidelines". The grey literature was used to supplement the search. All articles that provided guidance on opioid prescribing in breast surgery were included. Quality of the guidelines were assessed using the AGREE II tool. Recommendations pertaining to opioid prescribing, analgesic adjuncts and non-pharmacological interventions were summarised and reported with descriptive statistics. RESULT: Eight guidelines pertaining to mastectomies, breast conserving surgery and breast reconstructions were included in this review. Although an opioid-sparing approach was unanimous, there were conflicting recommendations on opioid doses. Opioid requirements were stratified by procedure in 3 guidelines, and by patient risk factors in 2 guidelines. There was significant variability in the recommended multimodal adjuncts. Notably, non-pharmacological interventions such as patient education were infrequently included in guidelines. CONCLUSION: There is a lack of high-quality guidance on opioid prescribing after breast surgery. The optimum approach for personalised opioid prescribing remains unknown. Significant variability between guidelines provide little actionable interventions for prescribers. This could be driven by the paucity in evidence supporting a single efficacious analgesic regimen for patients undergoing breast surgery. Future guidelines should also regularly incorporate non-pharmacological adjuncts to reduce opioid prescribing.

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers.

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.

Lymph Node Ratio in Sentinel Lymph Node Biopsy Era: Are We Losing Prognostic Information?

BACKGROUND: The number of involved axillary lymph nodes (LNs) found pathologically is regarded as a significant prognostic factor in early-stage breast cancer (EBC). Recently, there is speculation that LN ratio (LNR) may be a better surrogate at predicting cancer-specific outcome than number of involved LNs. This study investigated prognostic value of LNR, using predetermined cutoff values. METHODS: Data included all women diagnosed with node-positive EBC between January 1, 2001, and December 31, 2010 (N = 553). Retrospective evaluation for clinical, demographic, and pathologic data was performed. Most had axillary node clearance (ANC) (548/553; 99.1%). Cohorts were divided by LNR risk groups (low: ≤ 0.20; intermediate: 0.21-0.65; high: >0.65). Proportional hazard modeling was undertaken to evaluate whether LNR was associated with overall survival (OS). RESULTS: Median follow-up was 59.8 months. LNR distribution was as follows: low, 303/553 (54.8%); intermediate, 160/553 (28.9%); high, 90/553 (16.3%). Kaplan-Meier estimates for OS were stratified by LNR: low-risk group had better outcome for OS (P < .001). Overall 5- and 10-year OS was 63% and 58%, respectively. Number of positive LNs correlated with 10-year OS (66%, 48%, and 48% for patients with N1, N2, and N3 stage, respectively; P < .001). LNR also correlated with 5-year OS (69%, 48%, and 41% for low-, intermediate-, and high-risk groups, respectively; P < .001). Significantly, LNR on multivariate analysis also formed a prognostic model when combined with age, estrogen receptor status, PgR status and, HER2 status (P < .001). CONCLUSION: The Findings support LNR as a predictor for OS in EBC. LNR should be considered an independent prognostic variable to current prognostic instruments already in use.

Lower gastrointestinal bleeding in the elderly: a rare aetiology masquerading as a diverticular bleed.

Bleeding per rectum is a relatively common acute surgical presentation. Common causes include diverticular disease, colitis, haemorrhoids, polyps, etc. An 83-year-old man with a history of recurrent rectosigmoid diverticulitis and bilateral internal iliac artery aneurysms for 2 years presented with rectal bleeding. He was suspected to have a diverticular bleed based on history and examination. A CT scan revealed a large haematoma adjacent to the right isolated internal iliac artery aneurysm (IIIAA) almost indistinguishable from the adjacent rectosigmoid, consistent with a ruptured IIIAA and an ileorectal fistula. The fistula was of a primary vascular enteric type and was accentuated by the inflammation arising from the diverticulitis. Hence, presence of more common or apparently obvious causes should not deter clinicians from thoroughly investigating the case. Rare causes should be kept in mind while dealing with common acute presentations, especially in elderly patients with multiple comorbidities.