Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Propensity-Matched Analysis of Postoperative Complications Using ACS-NSQIP.

BACKGROUND: The use of neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is increasing. While there is an association between NAT and improved post-pancreatectomy complication rates in limited patient populations, the strength of the relationship and its applicability to a broader and modern pancreatectomy cohort remains unclear. METHODS: We used the 2014-2018 American College of Surgeons National Surgical Quality Improvement Project to evaluate NAT use for PDAC patients undergoing pancreatectomy. We also used propensity score matching techniques to compare 30-day postoperative outcomes, including clinically relevant postoperative pancreatic fistula (CR-POPF) and delayed gastric emptying (DGE), between patients selected for NAT versus upfront surgery. RESULTS: Patients receiving NAT were more likely to undergo vascular resections (33% vs. 16%, p < 0.001), have perioperative transfusions (18% vs. 12%, p < 0.001), and undergo longer procedures. Rates of CR-POPF (6%, vs. 10%, p < 0.001), DGE (11% vs. 13%, p = 0.016), postoperative percutaneous drainage (9% vs. 12%, p < 0.001), and SSI (15% vs. 18%, p < 0.001) were lower for patients selected for NAT. The association of NAT with CR-POPF remained statistically significant (adjusted odds ratio 0.52, 95% CI 0.42-0.66) after adjustment for operative technique, gland texture, and need for vascular resection for patients undergoing pancreaticoduodenectomy, but not for patients undergoing distal pancreatectomy. CONCLUSIONS: Among PDAC patients undergoing resection, selection for NAT is associated with fewer CR-POPFs, postoperative procedural interventions, and infectious complications, particularly for patients undergoing pancreaticoduodenectomy. These associations should be considered in discussions of multidisciplinary treatment sequencing for patients with PDAC.

Preoperative nomogram to predict posthepatectomy liver failure.

BACKGROUND AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is associated with significant morbidity and mortality. However, it is often difficult to predict the risk of PHLF in an individual patient. We aimed to develop a preoperative nomogram to predict PHLF and allow better risk stratification before surgery. METHODS: Data for patients undergoing a partial or major hepatectomy were extracted from the hepatectomy-specific NSQIP database for years 2014-2016. Data set from 2017 was used for validation. Patients with Grade B/C liver failure were compared with patients with no liver failure. RESULTS: A total of 10 808 patients from 2014-2016 data set were included. Of these, 316 patients (2.9%) developed Grade B/C PHLF. In the multivariable model consisting of preoperative variables, the following were predictive of Grade B/C PHLF (all p < 0.05): male gender, biliary stent, neoadjuvant therapy, viral hepatitis B or C, concurrent resections, biliary reconstruction, low sodium, and low albumin (model c statistic-0.78). This model was used to construct a nomogram. In the 2017 validation cohort of 4367 patients the nomogram again demonstrated good c-statistic (0.78). CONCLUSIONS: Our nomogram provides patient-specific probabilities for PHLF, and is easy to use. This is a valuable tool that can be utilized for preoperative patient counseling and selection.

Expression of green fluorescent protein in human foreskin fibroblasts for use in 2D and 3D culture models.

The availability of fibroblasts that express green fluorescent protein (GFP) would be of interest for the monitoring of cell growth, migration, contraction, and other processes within the fibroblast-populated collagen matrix and other culture systems. A plasmid lentiviral vector-GFP (pLV-GFP) was utilized for gene delivery to produce primary human foreskin fibroblasts (HFFs) that stably express GFP. Cell morphology, cell migration, and collagen contraction were compared between nontransduced HFFs and transduced GFP-HFFs; no differences were observed. Immunocytochemical staining showed no differences in cell morphology between nontransduced and GFP-HFFs in both two-dimensional and three-dimensional culture systems. Furthermore, there was no significant difference in cellular population growth within the collagen matrix populated with nontransduced vs. GFP-HFFs. Within the limits of our assays, we conclude that transduction of GFP into HFFs did not alter the observed properties of HFFs compared with nontransduced fibroblasts. The GFP-HFFs may represent a new tool for the convenient monitoring of living primary fibroblast processes in two-dimensional or three-dimensional culture.

The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats.

In patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats. Rats (CD IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored. Preoperative body weight was 884 ± 95 versus 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 versus 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% versus 5% decrease in high-fat versus low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups. The high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

Fluid administration rate for uncontrolled intraabdominal hemorrhage in swine.

BACKGROUND: We hypothesized that slow crystalloid resuscitation would result in less blood loss and a smaller hemoglobin decrease compared to a rapid resuscitation during uncontrolled hemorrhage. METHODS: Anesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapid vs. slow, respectively, N = 12 per group; limit of 100 mL/kg). Primary endpoints were blood loss and serum hemoglobin; secondary endpoints included survival, vital signs, coagulation parameters, and blood gases. RESULTS: The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL). CONCLUSIONS: Using a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a smaller hemoglobin decrease compared to rapid infusion.

Effect of proximal versus distal 50% enterectomy on nutritional parameters in rats preconditioned with a high-fat diet or regular chow.

Obesity may protect against the nutritional consequences of short bowel syndrome. We hypothesized that rats preconditioned with an obesogenic diet would have better outcomes after surgical induction of short bowel syndrome compared to rats on regular chow. Rats were fed a high-fat diet or regular rat chow for six months, and then underwent 50% proximal, 50% distal, or sham enterectomy. Food intake, weight, and body composition were monitored before and for 4 weeks after surgery. The high-fat diet consistently produced obesity (>25% body fat). All procedures induced weight loss, but there was no discernable difference between resection vs. sham resection. Rats on the high-fat diet had a greater post-resection loss of body fat compared to rats on chow (36 vs. 26 g, respectively). There was a nonsignificant trend of less lean mass loss in the former compared to the latter rats (16 vs. 33 g, respectively). Enterectomy moderated serum ghrelin, GIP, PPY, insulin, and leptin. Intestinal adaptation was not different between obese vs. non-obese rats. Rats preconditioned with the high-fat diet may have had better retention of lean body mass after a surgical procedure compared to rats on chow. The effect of 50% enterectomy was less than expected.

Development of a fatal noncompressible truncal hemorrhage model with combined hepatic and portal venous injury in normothermic normovolemic swine.

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ∼ 50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34-36 kg) underwent one of three injury types through a midline incision: 1) central stellate injury (N = 6); 2) excision of a portal vein branch distal to the main PV trunk (N = 6); or 3) hemi-transection of the left lateral lobe of the liver at its base (N = 10). The one-hour mortality of these injuries was 0, 82, and 40%, respectively; the final mean arterial pressure was 65, 24, and 30 mm Hg, respectively; and the final hemoglobin was 8.3, 2.3, and 3.6 g/dL, respectively. Hemi-transection of the left lateral lobe of the liver appeared to target our desired mortality rate better than the other injury mechanisms.