Purpose Guidelines regarding the prevention, detection, and management of surgical site infections (SSI) have been published previously.1-3 This document is intended to update prior guidelines based ...on the current literature and to provide a concise summary of relevant topics.
An Unusual Sequela of Longstanding Gallstone Disease LaRocca, Christopher J.; Prathibha, Saranya; Jensen, Eric H.
Gastroenterology (New York, N.Y. 1943),
July 2023, 2023-07-00, Letnik:
165, Številka:
1
Journal Article
Background
Multiple trials have demonstrated a survival benefit for adjuvant chemotherapy after resection of pancreatic adenocarcinoma. This study aimed to identify the rate for completion of ...adjuvant chemotherapy, factors associated with completion, and its impact on survival after surgical resection.
Methods
The Surveillance Epidemiology and End Results Medicare-linked data was used to identify patients who underwent upfront resection for pancreatic adenocarcinoma from 2004 to 2013. Billing codes were used to quantify receipt and completion of chemotherapy. Factors associated with completion of chemotherapy were identified using multivariable regression. Kaplan–Meier and Cox proportional-hazards modeling were used to examine survival.
Results
The inclusion criteria were met by 2440 patients. Of these patients, 65% received no adjuvant chemotherapy, 28% received incomplete therapy, and 7% completed chemotherapy. The factors associated with chemotherapy completion were nodal metastases and treatment at a National Cancer Institute-designated cancer center (
p
≤ 0.05). Comorbidities decreased the odds of completion (
p
≤ 0.05). The median overall survival (OS) was 14 months for the patients who received no adjuvant chemotherapy, 17 months for those who received incomplete adjuvant chemotherapy, and 22 months for those who completed adjuvant chemotherapy (
p
≤ 0.05). More recent diagnosis, comorbidities, T stage, nodal metastases, and no adjuvant chemotherapy were associated with an increased hazard ratio for death (
p
≤ 0.05). Evaluation of 15 or more nodes and completion of chemotherapy decreased the hazard ratio for death (
p
≤ 0.05).
Conclusions
Only 7% of the Medicare patients who underwent upfront resection for pancreatic cancer completed adjuvant chemotherapy, yet completion of adjuvant chemotherapy was associated with improved OS. Completion of adjuvant chemotherapy should be the goal after upfront resection, but neoadjuvant chemotherapy may ensure that patients receive systemic chemotherapy.
Neuroendocrine tumors are a heterogeneous group of tumors originating in various anatomic locations. The management of this disease poses a significant challenge because of the heterogeneous clinical ...presentations and varying degrees of aggressiveness. The recent completion of several phase 3 trials, including those evaluating octreotide, sunitinib, and everolimus, demonstrate that rigorous evaluation of novel agents in this disease is possible and can lead to practice-changing outcomes. Nevertheless, there are many aspects to the treatment of neuroendocrine tumors that remain unclear and controversial. The North American Neuroendocrine Tumor Society published a set of consensus guidelines in 2010, which provided an overview for the treatment of patients with these malignancies. Here, we present a set of consensus tables intended to complement these guidelines and serve as a quick, accessible reference for the practicing physician.
Purpose
The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 ...positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs.
Methods
Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer).
Results
We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22).
Conclusion
Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.
Introduction Sorafenib is the only drug approved by the Food and Drug Administration for metastatic hepatocellular carcinoma (HCC). Triptolide, a diterpene triepoxide, exhibits antineoplastic ...properties in multiple tumor cell types. In this study, we examined the effects of these agents and their combination on HCC in vitro and in vivo models. Methods HuH-7 and PLC/PRF/5 cells were treated with triptolide (50 nM), sorafenib (1.25 or 2.5 μM), or a combination of both. Cell viability assay (CCK-8), caspase 3&7 activation, and nuclear factor κB assays were performed. For in vivo studies, 40 mice were implanted with subcutaneous HuH7 tumors and divided into four treatment groups ( n = 10); saline control, sorafenib 10 mg/kg PO daily (S), Minnelide (a prodrug of triptolide) 0.21 mg/kg intraperitoneally7 daily (M), and combination of both (C). Tumor volumes were assessed weekly. Results The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis and decreasing viability, whereas triptolide alone was sufficient to decrease nuclear factor κB activity. After 2 weeks of treatment, tumor growth inhibition rates were S = 59%, M = 84%, and C = 93%, whereas tumor volumes in control animals increased by 9-fold. When crossed over to combination treatment, control mice tumor growth volumes plateaued over the following 4 weeks. Conclusion The combination of sorafenib and triptolide is superior to single drug treatment in increasing cell death and apoptosis in vitro. Combining sorafenib with Minnelide inhibited tumor growth with greater efficacy than single-agent treatments. Importantly, in vivo combination treatment allowed for using a lesser dose of sorafenib (10 mg/kg), which is less than 10% of currently prescribed dose for HCC patients. Therefore, combination treatment could have translational potential in the management of HCC.
Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but ...it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2–ABA–PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a gate that closes in response to ABA by way of conformational changes in two highly conserved β-loops that serve as a gate and latch. Moreover, ABA-induced closure of the gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the gate and latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved gate–latch–lock mechanism underlying ABA signalling.
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