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BACKGROUND: Biofilms represent a complex milieu of matrix-enclosed microorganisms, which can significantly contribute to the pathology of chronic wounds. In this study, we compare the activity of three commercial antimicrobial wound-care solutions, Vashe® (HOCl-based), PhaseOne® (HOCl-based), and Sulfamylon® (mafenide acetate), for their in vitro activity against bacterial and fungal biofilms. METHODS: Reference and clinical isolates of 6 Gram-negative bacterial species (36 total strains), 3 Gram-positive bacteria (21 strains), and 3 Candida species (9 strains) were used to create biofilms. Various working concentrations of the 3 antiseptic agents were incubated with the biofilms in microwell plates; they were monitored from 1 minute to 24 hours to compare bacterial and fungal viability through colony forming unit (CFU) analysis. RESULTS: Vashe® and PhaseOne® displayed excellent bactericidal and fungicidal activity, whereas Sulfamylon® demonstrated minimal activity against the biofilms tested. With the exception of C. albicans, all biofilms were eliminated at either 1 or 10 minutes using Vashe® and PhaseOne® solutions. In most cases, mafenide was unable to eliminate both bacterial and fungal biofilms, even with 24 hours of treatment. CONCLUSIONS: Biofilms represent a major clinical challenge, with no clear consensus for treatment of chronic wounds or prosthetic devices. Our results suggest that hypochlorous acid-based wound solutions such as Vashe® and PhaseOne® are more efficacious than mafenide in eliminating bacterial and fungal biofilms. Further studies are necessary to investigate and compare the in vivo efficacy of these products in clinical care.

Background and Objectives While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown. Methods A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses. Results Median patient age was 58 years (IQR, 50.4–66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597). Conclusions KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Background Investigations regarding the impact of tumor biology after surgical management of colorectal liver metastasis have focused largely on overall survival. We investigated the impact of codon-specific KRAS mutations on the rates and patterns of recurrence in patients after surgery for colorectal liver metastasis (CRLM). Methods All patients who underwent curative-intent surgery for CRLM between 2002 and 2015 at Johns Hopkins who had available data on KRAS mutation status were identified. Clinico-pathologic data, recurrence patterns, and recurrence-free survival (RFS) were assessed using univariable and multivariable analyses. Results A total of 512 patients underwent resection only (83.2%) or resection plus radiofrequency ablation (16.8%). Although 5-year overall survival was 64.6%, 284 (55.5%) patients recurred with a median RFS time of 18.1 months. The liver was the initial recurrence site for 181 patients, whereas extrahepatic recurrence was observed in 162 patients. Among patients with an extrahepatic recurrence, 102 (63%) had a lung recurrence. Although overall KRAS mutation was not associated with overall RFS (P = 0.186), it was independently associated with a worse extrahepatic (P = 0.004) and lung RFS (P = 0.007). Among patients with known KRAS codon-specific mutations, patients with codon 13 KRAS mutation had a worse 5-year extrahepatic RFS (P = 0.01), whereas codon 12 mutations were not associated with extrahepatic (P = 0.11) or lung-specific recurrence rate (P = 0.24). On multivariable analysis, only codon 13 mutation independently predicted worse overall extrahepatic RFS (P = 0.004) and lung-specific RFS (P = 0.023). Conclusions Among patients undergoing resection of CRLM, overall KRAS mutation was not associated with RFS. KRAS codon 13 mutations, but not codon 12 mutations, were associated with a higher risk for overall extrahepatic recurrence and lung-specific recurrence. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2698-2707. © 2016 American Cancer Society.

The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy. Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV2m-RLVp)/RLVp] and 7 months[(RLV7m-RLVp)/RLVp] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed. On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P > 0.05) and RLV/TLV at surgery (P = 0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P = 0.01) with these patients having increased risk for postoperative liver failure (P = 0.01). The inhibition of liver regeneration persisted at 7 months (P = 0.007) and was associated with a worse survival (P = 0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P = 0.02). Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.

Duodenal neuroendocrine tumors (NETs) are rare neoplasms with poorly defined management. We sought to evaluate the outcomes of patients undergoing resection of duodenal NETs.Using a multi-institutional database, 146 patients who underwent resection for duodenal NETs between 1993 and 2015 were identified. Data on clinicopathologic characteristics and outcomes were collected and analyzed.Local surgical resection (LR) was performed in 57 (39.0 %) patients, while 50 (34.3 %) patients underwent pancreaticoduodenectomy (PD) and 39 (26.7 %) patients an endoscopic resection (ER). Factors associated with worse RFS included advanced tumor grade and metastasis at diagnosis (both P 0.05) but not procedure type (P 0.05). Among patients who had at least one lymph node examined (n = 85), 50 (58.8 %) had a metastatic lymph node; lymph node metastasis (P = 0.04) and advanced tumor grade (P = 0.04) were more common among patients with tumors1.5 cm. Median length-of-stay was longer for PD versus LR (P 0.001). PD patients were at increased risk for severe postoperative complications (P = 0.01).Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors ≤1.5 cm, LR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.

Background: While reduction of portal venous (PV) blood flow has been described in animal models of intra-abdominal hypertension, reports on compensatory changes in hepatic arterial (HA) flow, known as the hepatic arterial buffer response are controversial. Materials and Methods: Pneumoperitoneum with helium was induced in 13 piglets. Hemodynamic measurements and pathological assessment were conducted at baseline and during the three subsequent phases: Phase A: 45 minutes with a stable intra-abdominal pressure of 25 mmHg; phase B: 45 minutes with a stable intra-abdominal pressure of 40 mmHg; and phase C during which the abdomen was re-explored and reperfusion of the liver was allowed to take place. Results: Phase B pressure was significantly greater than phase A pressure in both the PV and the inferior vena cava, demonstrating a positive association between escalating intra-abdominal hypertension and the pressure in these two vessels (all p

The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42-3.30; P 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73-2.48; P = 0.348).The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.

The influence of intraoperative blood loss (IBL) on long-term outcomes of patients undergoing liver resection for colorectal cancer liver metastases (CRLM) remains not well defined.A total of 433 patients who underwent curative-intent hepatic resection for CRLM between 2000 and 2013 at Johns Hopkins were identified. Demographics, IBL data, and long-term outcomes were collected and analyzed. Clinicopathologic predictors of IBL and the association of IBL and outcomes were assessed.The median patient age was 54 y (interquartile range, 44-64), most patients were male (58.9%; n = 255). At surgery, the median IBL was 400 mL (range, 10-5100 mL). Two-hundred eighty-seven patients (66.3%) had an IBL of250 mL. Factors associated with increased IBL (250 mL) on multivariate analysis were male sex (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.68-4.09; P 0.001), tumor size3 cm (OR, 1.88; 95% CI, 1.18-2.99; P = 0.008), and major hepatic resection (OR, 3.08; 95% CI, 1.92-4.92; P 0.001). At a median follow-up time of 30.6 mo, the median survival times were 70.5, 56.4, and 36.9 mo for IBL250, 250-1000, and1000 mL, respectively (P = 0.004). IBL250 mL remained an independent prognostic factor of overall survival in multivariate analysis (hazard ratio, 1.41; 95% CI, 1.01-1.97; P = 0.04) after adjusting for other factors including the receipt of blood transfusion.The magnitude of IBL during CRLM resection was related to biologic characteristics of the tumor and the extent of surgery. Increased IBL during CRLM resection was an independent prognostic factor for worse patient survival. Furthermore, a dose-response relationship between increasing IBL and worsening survival was evident.

255 Background: Duodenal neuroendocrine tumors (NETs) are rare neoplasms and their management is poorly defined. As such, we sought to evaluate the management and outcomes of patients undergoing resection of duodenal NETs. Methods: Using a multi-institutional database, 132 patients who underwent curative-intent resection for duodenal NETs between 1998 and 2015 were identified. Data on clinical characteristics, comorbidities, procedural details, as well as recurrence-free survival (RFS) were collected and analyzed. Results: Median age was 63 years and most patients were male(52.3%). Two-thirds(66.7%) of patients had symptomatic disease. Most patients presented with abdominal pain(47.8%), while 17(19.3%) patients presented with GI bleeding/anemia. Lesions were located in first/second(94.5%) or third/fourth(5.5%) portion of the duodenum. Median tumor size was 1.7 cm. Local surgical resection(LSR) was performed in 55(42.0%) patients, while 47(35.9%) patients underwent pancreaticoduodenectomy(PD) and 29(22.1%) underwent an endoscopic resection(ER). Most patients had an R0 surgical margin(88.4%)(LSR, 88.7% vs. PD, 95.7% vs. ER, 71.4%; P = 0.02). Among patients who had at least one lymph node examined(n = 86), 49(57.0%) had a metastatic lymph node; lymph node metastasis were more common among patients with tumors ≥ 2cm(OR = 3.21, P = 0.02). Median length-of-stay was longer for PD(11 days) versus LSR(7 days)(P < 0.001). PD patients had more complications(LSR, 52.7% vs. PD, 63.8% vs. ER, 6.9%; P < 0.001). 3- and 5-year RFS was 80.1%, and 69.6%, respectively (site of recurrence: locoregional, n = 8 vs. distant, n = 14). Factors associated with worse RFS included tumor grade(moderate-to-poor: HR 4.12) and presence of metastasis at diagnosis (HR 5.66)(both P < 0.05). PD versus LSR versus ER approach was not associated with RFS (P > 0.05). Conclusions: Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors < 2cm, LSR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.