Early Postoperative Vital Signs Predict Subsequent 90-Day Mortality After Pancreaticoduodenectomy.

BACKGROUND: While complication rates after pancreaticoduodenectomy (PD) have improved in recent decades, surgical-related death remains a possibility. Postoperative vital signs offer an untapped opportunity to identify predictors of 90-day mortality. METHODS: We performed a retrospective chart review interrogating postoperative day (POD 0-7) vital sign measurements from patients undergoing a PD at Thomas Jefferson University Hospital, Philadelphia, PA (2009-2014). Five specific vital signs were examined as predictors of mortality: temperature, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure. Statistical analyses and logic algorithms were employed to rank vital sign parameters, with cut-points, to identify those associated with the highest risk of mortality and the most clinical relevance. RESULTS: In our cohort, 11/750 patients (1.5%) died within 30 days of surgery, and 21/750 patients (2.8%) died within 90 days of surgery. Vital sign perturbations associated with the highest risk of mortality included mean SBP < 95 mmHg on POD 7 (odds ratio 51.46) and the mean temperature < 96.9℉ on POD 3 (odds ratio 22.63) with specificities exceeding 99%. The most clinically relevant predictor (i.e., a higher sensitivity) was DBP < 60.5 mmHg on POD 7 (odds ratio 12.45, sensitivity of 75%). These predictors remained statistically significant in a multivariable model. CONCLUSIONS: Vital signs can be more effectively utilized to predict 90-day mortality after pancreaticoduodenectomy. Values beyond an informative threshold can potentially identify patients for more intensive monitoring with a goal of rescuing patients and preventing death.

The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA-approved antihelminthic pyrvinium pamoate (PP) has previously been shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50 values (9-93 nmol/L) against a panel of PDAC, patient-derived, and murine organoid cell lines. In vivo, we demonstrated that PP inhibited PDAC xenograft tumor growth with both intraperitoneal (IP; P < 0.0001) and oral administration (PO; P = 0.0023) of human-grade drug. Metabolomic and phosphoproteomic data identified that PP potently inhibited PDAC mitochondrial pathways including oxidative phosphorylation and fatty acid metabolism. As PP treatment reduced oxidative phosphorylation (P < 0.001), leading to an increase in glycolysis (P < 0.001), PP was 16.2-fold more effective in hypoglycemic conditions similar to those seen in PDAC tumors. RNA sequencing demonstrated that PP caused a decrease in mitochondrial RNA expression, an effect that was not observed with established mitochondrial inhibitors rotenone and oligomycin. Mechanistically, we determined that PP selectively bound mitochondrial G-quadruplexes and inhibited mitochondrial RNA transcription in a G-quadruplex-dependent manner. This subsequently led to a 90% reduction in mitochondrial encoded gene expression. We are preparing to evaluate the efficacy of PP in PDAC in an IRB-approved window-of-opportunity trial (IND:144822).

Minimally invasive management of de Garengeot hernia with staged robotic hernia repair.

De Garengeot hernia is a rare phenomenon describing the migration of the appendix into a femoral hernia sac. Many repair strategies have been described although an open inguinal approach with suture repair is the most common technique. Despite strong evidence that mesh limits recurrence, most forgo mesh use in the presence of appendicitis for fear of contamination. We report a case in a 68-year-old man managed completely with minimally invasive strategies. We performed a staged laparoscopic appendectomy followed by robotic hernia repair with polypropylene mesh. This is the first described two-stage minimally invasive approach and the first report demonstrating the feasibility of robotic hernia repair in the setting of de Garengeot hernia. It is our opinion that using a staged approach may encourage mesh repair by minimising the risk of implant contamination. Furthermore, we believe a fully minimally invasive technique may result in improved outcomes.

Accuracy of cytopathology evaluation for resected benign and malignant pancreatic disease.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the preferred method for diagnosing pancreatic masses. While the diagnostic success of EUS-FNA is widely accepted, the actual performance of EUS-FNA is not known. This study sought to define the EUS-FNA accuracy compared with the gold standard, surgically resected specimens. The study was a single institution, retrospective, and chart review of patients with surgically resected pancreatic specimens from 2005 to 2015 with a preoperative EUS-FNA or biliary brushing. Cytological reports were organized from least concerning (i.e., low chance of malignancy) to most concerning (high chance of malignancy) into eight cytologic categories. We identified 741 cytologic cases: 530 EUS-FNA and 211 endoscopic brushings. For EUS-FNA samples, 62.5% of "benign" samples proved to be "benign" on surgical pathology. A cytologic diagnosis of "suspicious for malignancy" or "positive for malignancy" were concordant with a cancer diagnosis on surgical pathology 93.3% and 98.0% of cases, respectively. EUS-FNA proved to be highly reliable at diagnosing malignancy for cytologic samples that were "suspicious" or "positive" for malignancy. Paired with supportive clinical data, these interpretations may be used to justify cancer treatment.