Rare long-term survivors of pancreatic adenocarcinoma without curative resection

Long-term outcome data in pancreatic adenocarcinoma are predominantly based on surgical series, as resection is currently considered essential for longterm survival. In contrast, five-year survival in nonresected patients has rarely been reported. In this report, we examined the incidence and natural history of ≥ 5-year survivors with non-resected pancreatic adenocarcinoma. All patients with pancreatic adenocarcinoma who received oncologic therapy alone without surgery at our institution between 1995 and 2009 were identified. Non-resected ≥ 5-year survivors represented 2%(11/544) of all non-resected patients undergoing treatment for pancreatic adenocarcinoma, and 11%(11/98) of ≥ 5-year survivors. Nine patients had localized tumor and 2 metastatic disease at initial diagnosis. Disease progression occurred in 6 patients, and the local tumor bed was the most common site of progression. Six patients suffered from significant morbidities including recurrent cholangitis, second malignancy, malnutrition and bowel perforation. A rare subset of patients with pancreatic cancer achieve longterm survival without resection. Despite prolonged survival, morbidities unrelated to the primary cancer were frequently encountered and a close follow-up is warranted in these patients. Factors such as tumor biology and host immunity may play a key role in disease progression and survival.

Contemporary,national patterns of surgery after preoperative therapy for stageⅡ/Ⅲrectal adenocarcinoma

BACKGROUND Contemporary treatment of stageⅡ/Ⅲrectal cancer combines chemotherapy,chemoradiation,and surgery,though the sequence of surgery with neoadjuvant treatments and benefits of minimally-invasive surgery(MIS)is debated.AIM To describe patterns of surgical approach for stageⅡ/Ⅲrectal cancer in relation to neoadjuvant therapies.METHODS A retrospective cohort was created using the National Cancer Database.Primary outcome was rate of sphincter-sparing surgery after neoadjuvant therapy.Secondary outcomes were surgical approach(open,laparoscopic,or robotic),surgical quality(R0 resection and 12+lymph nodes),and overall survival.RESULTS A total of 38927 patients with clinical stageⅡorⅢrectal adenocarcinoma underwent surgical resection from 2010-2016.Clinical stageⅡpatients had neoadjuvant chemoradiation less frequently compared to stageⅢ(75.8%vs 84.7%,P<0.001),but had similar rates of total neoadjuvant therapy(TNT)(27.0%vs 27.2%,P=0.697).Overall rates of total mesorectal excision without sphincter preservation were similar between clinical stageⅡandⅢ(30.0%vs 30.3%)and similar if preoperative treatment was chemoradiation(31.3%)or TNT(30.2%).Over the study period,proportion of cases approached laparoscopically increased from 24.9%to 32.5%and robotically 5.6%to 30.7%(P<0.001).This cohort showed improved survival for MIS approaches compared to open surgery(laparoscopy HR 0.85,95%CI 0.78-0.93,and robotic HR 0.82,95%CI 0.73-0.92).CONCLUSION Sphincter preservation rates are similar across stageⅡandⅢrectal cancer,regardless of delivery of preoperative chemotherapy,chemoradiation,or both.At a national level,there is a shift to predominantly MIS approaches for rectal cancer,regardless of whether sphincter sparing procedure is performed.

The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Special Issue:Emerging Investigators

Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.