Contemporary report of surgical outcomes after single-stage total pancreatectomy: A 10-year experience.

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients. METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed. RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6). CONCLUSION: Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Longitudinal Strain Patterns in Stress (Takotsubo) Cardiomyopathy: Evidence of Global Myocardial Injury and Incomplete Recovery.

Stress cardiomyopathy develops after abrupt sympathetic stimulation, likely from catecholamine-induced myocardial toxicity. The evolution of myocardial strain during and after an episode have not been previously characterized. We aimed to determine whether preexisting contractile abnormalities may explain the observed regional dysfunction during an acute episode and to investigate the persistence of strain abnormalities after clinical recovery. We identified patients who were diagnosed with stress cardiomyopathy and had an echocardiogram performed before their episode, during their episode, and within 1 year after. The diagnosis was confirmed based on the absence of obstructive coronary lesions. Left ventricular (LV) longitudinal strain was calculated using speckle-tracking software and compared between baseline, episode, and follow-up echocardiograms. The LV strain analysis was performed on 23 patients. The LV ejection fraction was 64 ± 8.7% at baseline, 45 ± 12% during the episode, and 5 9 ± 10% after a median follow-up of 46 days. The LV global longitudinal strain was 24 ± 4.7% at baseline, 11 ± 4.9% during the episode, and 19 ± 4.6% after the follow-up. The mean ejection fraction (p <0.01) and global longitudinal strain (p <0.001) remained below baseline levels at follow-up. Longitudinal strain was reduced (<18%) in 80 ± 23% of myocardial segments during an episode and 41 ± 21% of myocardial segments at follow-up. During the acute episode, 35 ± 6% of the abnormal segments were in the base, outside of the region of ballooning. Our findings suggests that stress cardiomyopathy is associated with global rather than regional myocardial injury and that contractile abnormalities persist after clinical improvement. These findings challenge our previous understanding of stress cardiomyopathy and may guide future pathophysiologic understanding of this complex disease.

Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates. METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug's PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer. ETHICS AND DISSEMINATION: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05055323.

Implementation of an opioid reduction toolkit in pancreatectomy patients significantly increases patient awareness of safe practice and decreases amount prescribed and consumed.

BACKGROUND: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy patients. METHODS: Prescription, consumption, and refill request data for postoperative opioids were collected from patients receiving an open pancreatectomy before and after the implementation of an opioid reduction toolkit. Outcomes included safe disposal practice awareness for unused medication. RESULTS: 159 patients were included in the study: 24 in the pre-intervention and 135 in the post-intervention group. No significant demographic or clinical differences existed between groups. Median morphine milliequivalents (MMEs) prescribed were significantly reduced from 225 (225-310) to 75 (75-113) in the post-intervention group (p < 0.0001). Median MMEs consumed were significantly reduced from 109 (111-207) to 15 (0-75), p < 0.0001), as well. Refill request rates remained equivalent during the study (Pre: 17% v Post: 13%, p = 0.9) while patient awareness of safe disposal increased (Pre: 25% v Post: 62%, p < 0.0001). DISCUSSION: An opioid reduction toolkit significantly reduced the number of postoperative opioids prescribed and consumed after open pancreatectomy, while refill request rates remained the same and patients' awareness of safe disposal increased.

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. CASE PRESENTATION: Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). CONCLUSIONS: Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.

Risk Factors, Imaging Findings, and Sex Differences in Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is increasingly being recognized. However, data supporting diagnosis and management are scarce. We analyze a contemporary and comprehensive SCAD registry to advance the understanding of SCAD risk factors, angiographic appearance, and gender differences. This is a retrospective analysis of a prospectively populated database of SCAD patients seen at the Massachusetts General Hospital (MGH) between June 2013 and October 2017. Core laboratory analysis of both coronary angiograms and computerized tomographic (CT) angiography of the extracoronary vessels was performed. Of the 113 patients, 87% were female and mean age was 47 ± 10 years. Traditional cardiovascular risk factors including hypertension, hyperlipidemia, and smoking were present in 27%, 14%, and 22% of patients. Among females, 14%, 8%, and 9% had a history of gestational hypertension, pre-eclampsia, and gestational diabetes, respectively. Fifteen percent had used fertility treatment and 47% of postmenopausal women had used hormone replacement therapy. Angiography showed multivessel SCAD in 42%, severe coronary artery tortuosity in 59%, and extracoronary vascular abnormalities in 100% of patients with complete CT angiographic imaging. Gender differences revealed a self-reported depression and anxiety prevalence of 20% and 32%, respectively, in women compared with 0% in men. Type 1 SCAD was more commonly diagnosed in men than women (71% vs 29%, p <0.01). In conclusion, we highlight under-recognized features of SCAD including (1) relation with pregnancy complications and exposure to hormonal therapy; (2) diffuse, multivessel process in tortuous coronaries on a background of extracoronary arterial abnormalities; and (3) gender differences highlighting the role of mental health as well as potential underdiagnoses in men.

Prospective Cardiovascular Genetics Evaluation in Spontaneous Coronary Artery Dissection.

BACKGROUND: Previous studies describing genetics evaluation in spontaneous coronary artery dissection (SCAD) have been retrospective in nature or presented as single case reports. As part of a dedicated clinical program, we evaluated patients in cardiovascular genetics clinic to determine the role of genetically triggered vascular disease and genetic testing in SCAD. METHODS AND RESULTS: Patient data were entered prospectively into the Massachusetts General Hospital SCAD registry database from July 2013 to September 2017. Clinically indicated genetic testing was conducted based on patient imaging, family history, physical examination, and patient preference. Of the 107 patients enrolled in the registry, 73 underwent cardiovascular genetics evaluation at our center (average age, 45.3±9.4 years; 85.3% female), and genetic testing was performed for 44 patients. A family history of aneurysm or dissection was not a prevalent feature in the study population, and only 1 patient had a family history of SCAD. Six patients (8.2%) had identifiable genetically triggered vascular disease: 3 with vascular Ehlers-Danlos syndrome (COL3A1), 1 with Nail-patella syndrome (LMX1B), 1 with autosomal dominant polycystic kidney disease (PKD1), and 1 with Loeys-Dietz syndrome (SMAD3). None of these 6 had radiographic evidence of fibromuscular dysplasia. CONCLUSIONS: In this series, 8.2% of the SCAD patients evaluated had a molecularly identifiable disorder associated with vascular disease. The most common diagnosis was vascular Ehlers-Danlos syndrome. Patients with positive gene testing were significantly younger at the time of their first SCAD event. A low threshold for genetic testing should be considered in patients with SCAD.