Routine chest radiography after thoracostomy tube removal and during postoperative follow-up is not necessary after lung resection.

OBJECTIVES: The need for routine chest radiography following chest tube removal after elective pulmonary resection may be unnecessary in most patients. The purpose of this study was to determine the safety of eliminating routine chest radiography in these patients. METHODS: Patients who underwent elective pulmonary resection, excluding pneumonectomy, for benign or malignant indications between 2007 and 2013 were reviewed. Patients with in-hospital mortality or without routine follow-up were excluded. During this interval, our practice transitioned from ordering routine chest radiography after chest tube removal and at the first postoperative clinic visit to obtaining imaging based on symptomatology. The primary outcome was changes in management from results of chest radiography obtained routinely versus for symptoms. Characteristics and outcomes were compared using the Student t test and chi-square analyses. RESULTS: A total of 322 patients met inclusion criteria. Ninety-three patients underwent a routine same-day post-pull chest radiography, and 229 patients did not. Thirty-three patients (14.4%) in the nonroutine chest radiography cohort received imaging for symptoms, in whom 8 (24.2%) resulted in management changes. Only 3.2% of routine post-pull chest radiography resulted in management changes versus 3.5% of unplanned chest radiography with no adverse outcomes (P = .905). At outpatient postoperative follow-up, 146 patients received routine chest radiography; none resulted in a change in management. Of the 176 patients who did not have planned chest radiography at follow-up, 12 (6.8%) underwent chest radiography for symptoms. Two of these patients required readmission and chest tube reinsertion. CONCLUSIONS: Reserving imaging for patients with symptoms after chest tube removal and follow-up after elective lung resections resulted in a higher percentage of meaningful changes in clinical management.

Defining the operative time threshold for safety in patients undergoing robotic pancreaticoduodenectomy.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is a safe and efficacious procedure in appropriately selected patients, though frequently with increased operative times compared to open pancreaticoduodenectomy (OPD). METHODS: From 2014 to 2019, patients who underwent elective, low-risk, RPDs and OPDs in the NSQIP database were isolated. The operative time threshold (OTT) for safety in RPD patients was estimated by identifying the operative time at which complication rates for RPD patients exceeded the complication rate of the benchmark OPD control. RESULTS: Of 6270 patients identified, 939 (15%) underwent RPD and 5331 (85%) underwent OPD. The incidence of major morbidity or mortality for the OPD cohort was 35.1%. The OTT was identified as 7.7 h. Patients whose RPDs were above the OTT experienced a higher incidence of major morbidity (42.5% vs. 35.0%, p < 0.01) and 30-day mortality (2.7% vs. 1.2%, p = 0.03) than the OPD cohort. Preoperative obstructive jaundice (OR: 1.47, [95% CI: 1.08-2.01]) and pancreatic duct size <3 mm (OR: 2.44, [95% CI: 1.47-4.06]) and 3-6 mm (OR: 2.15, [95% CI: 1.31-3.52]) were risk factors for prolonged RPDs on multivariable regression. CONCLUSION: The operative time threshold for safety, identified at 7.7 h, should be used to improve patient selection for RPDs and as a competency-based quality benchmark.

Operative management of immune checkpoint colitis following in-transit melanoma: Case report.

Immune checkpoint inhibitors are increasingly used as powerful anti-neoplastic therapies in the setting of melanoma. Colitis is a known complication of immune checkpoint inhibitors that if often medically managed. We present a patient with stage IV melanoma with demonstrated in-transit disease undergoing immune checkpoint inhibitor therapy. The patient subsequently developed recalcitrant severe colitis that necessitated operative intervention and bowel resection. The association of immune check point inhibitors and immune related adverse effects are discussed as well as treatments of advanced colitis, including the possibility of surgical management in the setting of severe colitis with complications.

Incidence of Postoperative Complications Following Pancreatectomy for Pancreatic Cystic Lesions or Pancreatic Cancer.

BACKGROUND: In contrast to pancreatic ductal adenocarcinoma (PDAC), the risks of pancreatectomy for mucinous pancreatic cysts (MCs) are balanced against the putative goal of removing potentially malignant tumors. Despite undergoing similar operations, different rates of perioperative complications and morbidity between MC and PDAC patient populations may affect recommendations for resection. We therefore sought to compare the rates of postoperative complications between patients undergoing pancreatectomies for MCs or PDAC. METHODS: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for MCs or PDAC from July 2011 to August 2019. Patient demographics, complications, and perioperative data were compared between groups. RESULTS: A total of 103 patients underwent surgical resection for MCs and 428 patients underwent resection for PDAC. Combined major 90-day postoperative complications were similar between MC and PDAC patients undergoing pancreaticoduodenectomy (PD, 32.5% vs. 20.0%, p = 0.068) or distal pancreatectomy (DP, 30.2% vs. 20.5%, p = 0.172). The most frequent complications were postoperative pancreatic fistula (POPF), abscess, and postoperative bleeding. The incidence of 90-day ISGPS Grade B/C POPF was higher in cyst patients undergoing PD (17.5% vs. 4.1%, p = 0.003) but not DP (25.4% vs. 20.5%, p = 0.473). No significant differences in operative time or length of stay between MCs and PDAC cohorts were observed. CONCLUSIONS: POPFs occur more frequently and at higher grades in patients undergoing PD for MCs than for PDAC and should inform patient selection. Accordingly, the perioperative management of MC patients undergoing PD should emphasize POPF risk mitigation.

Total pancreatectomy and islet cell autotransplantation: a 10-year update on outcomes and assessment of long-term durability.

BACKGROUND: Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years. METHODS: Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively. RESULTS: Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months. CONCLUSION: This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.

A randomized, double-blind, multiple-dose study of the pan-genotypic NS5A inhibitor samatasvir in patients infected with hepatitis C virus genotype 1, 2, 3 or 4.

BACKGROUND & AIMS: Samatasvir is a pan-genotypic inhibitor of the hepatitis C (HCV) non-structural protein 5A (NS5A). This study evaluated the antiviral activity, pharmacokinetics and safety of samatasvir monotherapy in treatment-naïve subjects infected with HCV genotype 1-4. METHODS: Thirty-four genotype 1 and thirty genotype 2, 3 or 4 subjects were randomized to receive for 3days placebo or samatasvir 25-100mg per day. Plasma samples for HCV RNA, pharmacokinetics and sequencing were collected up to day 10. RESULTS: Samatasvir achieved potent antiviral activity across genotypes: mean maximum reductions from baseline were 3.2-3.6 (genotype 1a), 3.0-4.3 (genotype 1b), 3.2-3.4 (genotype 3), and 3.6-3.9 (genotype 4) log10/ml respectively; no viral rebound was observed during the 3-day treatment period. For genotype 2 HCV, samatasvir was active in subjects with NS5A L31 polymorphism at baseline (individual range 2.5-4.1 log10/ml), but showed minimal activity in those with baseline M31 polymorphism. Samatasvir exhibited a long plasma half-life of approximately 20h which supports once daily dosing. Samatasvir was well tolerated in all subjects with no safety-related discontinuations or serious adverse events. The most common adverse events included constipation, nausea and headache and occurred at similar frequency in active and placebo subjects. All events were mild or moderate in intensity. There were no patterns or dose dependence of adverse events, vital signs, laboratory parameters or electrocardiograms. CONCLUSIONS: Samatasvir 25-100mg monotherapy for 3days was well tolerated and induced a rapid and profound reduction in plasma HCV RNA in subjects infected with HCV genotype 1-4. Samatasvir is being evaluated in combination with other direct-acting antiviral agents in subjects with HCV infection.

Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis.

BACKGROUND: In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD. MATERIALS AND METHODS: In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression. RESULTS: Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03). CONCLUSIONS: Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.

Helping patients discuss CINV management: development of a Patient Charter.

In April 2012, an Expert Group of specialist cancer nurses working in a variety of settings (e.g. chemotherapy delivery, chemotherapy service design, research, nurse leadership and patient information/advocacy) participated in telephone/web-based meetings, with the aim of sharing current experience of chemotherapy-induced nausea and vomiting (CINV) management, and reaching a consensus on the development of a Patient Charter, designed to help patients understand CINV management, and setting out key questions they may wish to ask their healthcare professionals.

EGFR inhibition fails to suppress vascular proliferation and tumor growth in a Ewing's sarcoma model.

BACKGROUND: Expression of epidermal growth factor receptor (EGFR), a potent regulator of cellular homeostasis, is associated with aggressive tumor behavior. The mechanism by which EGFR inhibition functions is unclear, with controversial results demonstrating an effect on the tumor cells, endothelial cells, or pericytes. EGFR activation has been linked to the expression of vascular endothelial growth factor (VEGF), a known mitogen of angiogenesis, but the relationship between these factors and their effect on tumor vessel development is vague. We hypothesized that using an EGFR inhibitor on a human Ewing's sarcoma model would inhibit tumor growth by suppressing vessel proliferation. METHODS: A cell proliferation assay was performed on the Ewing's sarcoma (SK-NEP-1) cell line. Tumor cells were implanted intrarenally in athymic mice. Animals received daily gavage with vehicle or gefitinib 1 wk following implantation. Mice (n = 12/cohort) were euthanized 6 wk following implantation. Remaining mice were maintained without treatment for 2 wk. Vascular changes were assessed by angiography and immunohistochemically. EGFR and vascular endothelial growth factor (VEGF) expression were quantified using quantitative polymerase chain reaction (qPCR). RESULTS: Gefitinib suppressed in vitro cell growth with an IC(50) = 1.36 µM. Minimal tumor growth suppression was noted at 6 wk (6.01 ± 1.2 g in control versus 4.61 ± 0.9 g treated, P = 0.36). After cessation of gefitinib, tumor growth was increased in both groups (7.37 ± 1.62 g versus 6.77 ± 1.53 g, P = 0.79). Microvessel density was unchanged despite EGFR inhibition (161,000 ± 16,000 pixels versus 135,000 ± 18,000 pixels, P = 0.31). At 6 wk, the vascular maturity index was similar in both groups (3.63 ± 1.12 versus 4.09 ± 1.71, P = 0.83). A downward trend in EGFR expression (49% of control) and an upward trend in VEGF levels (50% of control) occurred in the treated group. CONCLUSIONS: EGFR expression was suppressed in cultured cells and xenograft tumors. Despite a cytotoxic effect on cell lines, gefitinib had little effect on tumor growth. No effects on the tumor vasculature were noted in the setting of EGFR suppression, suggesting that angiogenesis induced by SK-NEP-1 cells is refractory to EGFR inhibition. Interestingly, the resulting increase in VEGF expression following EGFR blockade, provides an alternative pro-angiogenic pathway promoting tumor survival.