Abstract Background Unlike many other types of cancer, improvements in the treatment of pancreatic cancer have been very limited, in part due to the inability to deliver chemotherapy to the tumor at efficacious concentrations for a prolonged time. PTM-101 is a novel biodegradable film containing paclitaxel and is designed to continuously release high concentrations of paclitaxel precisely to the site of a pancreatic tumor over one month. Methods This first in human study was conducted at one center in Australia to assess the safety, toxicity, and surgical feasibility of a single administration of PTM-101 containing 100 mg of paclitaxel. PTM-101 was sutured directly onto the pancreatic surface overlying the tumor by a surgical oncologist using standard laparoscopic equipment during a disease-staging assessment. Approximately 3 weeks after PTM-101 placement, all participants began standard of care therapy which included mFOLFIRINOX. This study enrolled 3 subjects that had treatment naïve, borderline resectable or locally advanced, pancreatic adenocarcinoma. Subjects were monitored closely for local and systemic toxicities, as well as for preliminary signals of efficacy. An independent central imaging lab reviewed CT scans to determine changes in tumor volume. Results PTM-101 was successfully implanted over the tumor site in all three subjects. In all cases, there were no adverse events reported during the procedure. Overall, PTM-101 was well tolerated with a total of five Grade 1 adverse events judged at least possibly related to the procedure or the mFOLFIRINOX. No serious adverse events (SAEs) or deaths occurred. Paclitaxel was undetectable in the circulation at all time points. Subjects were followed for 6 months. Best overall response rate according to RECIST was stable disease (2 subjects) and partial response (1 subject). An independent analysis showed that all tumors had a reduction in size in the anterior/posterior diameter, which was consistent with unidirectional paclitaxel release from PTM-101. Two of the 3 subjects had a >30% tumor volume reduction, importantly, with the initial decrease in tumor size detected prior to mFOLFIRINOX. Conclusion PTM-101 was readily implanted during diagnostic laparoscopy and was well tolerated with no SAEs or deaths reported during 6 months of follow up. This study demonstrated that a PTM-101 implant was surgically feasible, safe, resulted in no systemic paclitaxel exposure, and caused a tumor size reduction in all 3 subjects. Additional studies may demonstrate the potential for PTM-101 to be a first-line adjunct prior to neoadjuvant therapy in treatment naïve, borderline resectable or locally advanced, pancreatic cancer. Citation Format: Charles Pilgrim, Marty Smith, Ee-Jun Ban, Samantha Ellis, John Zalcberg, Benjamin Markman, Margaret Lashof-Sullivan, Laura Indolfi. First-in-human phase 1 study of paclitaxel-eluting PTM-101 film in subjects with borderline resectable or locally advanced pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT106.
BACKGROUND Acute colonic pseudo-obstruction (ACPO) is characterized by severe colonic distension without mechanical obstruction. It has an uncertain pathogenesis and poses diagnostic challenges. This study aimed to explore risk factors and clinical outcomes of ACPO in polytrauma patients and contribute information to the limited literature on this condition. METHODS This retrospective study, conducted at a Level 1 trauma center, analyzed data from trauma patients with ACPO admitted between July 2009 and June 2018. A control cohort of major trauma patients was used. Data review encompassed patient demographics, abdominal imaging, injury characteristics, analgesic usage, interventions, complications, and mortality. Statistical analyses, including logistic regression and correlation coefficients, were employed to identify risk factors. RESULTS There were 57 cases of ACPO, with an incidence of 1.7 per 1,000 patients, rising to 4.86 in major trauma. Predominantly affecting those older than 50 years (75%) and males (75%), with motor vehicle accidents (50.8%) and falls from height (36.8%) being the commonest mechanisms. Noteworthy associated injuries included retroperitoneal bleeds (RPBs) (37%), spinal fractures (37%), and pelvic fractures (37%). Analysis revealed significant associations between ACPO and shock index >0.9, Injury Severity Score >18, opioid use, RPBs, and pelvic fractures. A cecal diameter of ≥12 cm had a significant association with cecal ischemia or perforation. CONCLUSION This study underscores the significance of ACPO in polytrauma patients, demonstrating associations with risk factors and clinical outcomes. Clinicians should maintain a high index of suspicion, particularly in older patients with RPBs, pelvic fractures, and opioid use. Early supportive therapy, vigilant monitoring, and timely interventions are crucial for a favorable outcome. Further research and prospective trials are warranted to validate these findings and enhance understanding of ACPO in trauma patients. LEVEL OF EVIDENCE Prognostic and Epidemiological; Level IV.
Right atrial appendage rupture from blunt trauma is exceedingly rare, even more so when no other chest wall injuries are found. Very few cases have been documented with respect to survival from such an injury.To highlight the optimal management of such cases, namely through timely and safe transport to a trauma centre, maintaining a high degree of clinical suspicion for tamponade, early diagnostic ultrasound use, pericardial decompression, haemorrhage control and situational control.A case report delineating the diagnostic and therapeutic approach to an individual with right atrial appendage rupture. Subsequent post-operative and convalescent course till hospital discharge.A young male patient involved in a high-speed motor vehicle accident was hypotensive at the scene with altered sensorium. Transport to a trauma centre was delayed due to entrapment and geographical location. An ultrasound done on arrival identified cardiac tamponade, which was successfully treated with an emergent left lateral thoracotomy, pericardial decompression, and haemorrhage control from a ruptured right atrial appendage, with definitive closure in the operating theatre.Whilst rare, haemodynamic compromise in the absence of obvious thoracic trauma following high-energy, rapid deceleration mechanisms should raise suspicion for right atrial appendage rupture with pericardial tamponade. Aggressive resuscitation, early diagnostic ultrasound use and urgent pericardial decompression are essential in maximising the likelihood of positive outcomes.
Trauma to the pelvic ring and associated haemorrhage represent a management challenge for the multidisciplinary trauma team. In up to 10% of patients, bleeding can be the result of an arterial injury and mortality is reported as high as 89% in this cohort. We aimed to assess the mortality rate after pelvic trauma embolisation and whether earlier embolisation improved mortality.
Left hepatic trisectionectomy (LHT) is a complex hepatic resection; its' role and outcomes in hepatobiliary malignancies remains unclear.All patients undergoing LHT at the tertiary HPB referral unit at RSCH, Guildford, UK from September 1996 to October 2015 were included. Data were collected from a prospectively maintained database.Twenty-eight patients underwent LHT. The M:F ratio was 1.8:1. Median age was 60 years (range 43-76 years). Diagnoses included colorectal liver metastases (CRLM; n = 20); cholangiocarcinoma (CCA; n = 4); and other (neuroendocrine tumour metastases (NET; n = 3) and breast metastases (n = 1)). Median duration of surgery was 270 min (range 210-585 min). Median blood loss was 750 ml (300-2400 ml) with a perioperative transfusion rate of 21% (n = 6/28). The rate of all post-operative complications was 21% for all patients, and given the extensive resection performed four patients (14%) developed varying degrees of hepatic insufficiency. One patient with cholangiocarcinoma developed severe hepatic insufficiency, which was fatal within 90 days of surgery. 1 and 3-year survivals were 92% and 68% respectively.This study supports LHT in patients with significant tumour burden. Despite extensive resection, our favourable morbidity and mortality rates show this is a safe and beneficial procedure for patients with all hepatobiliary malignancies. Given the nature of resection the incidence of post-operative hepatic insufficiency is higher than less extensive hepatic resections.
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