Healthcare worker safety program in a coronavirus disease 2019 (COVID-19) alternate care site: The Javits New York Medical Station experience.

OBJECTIVE: In March 2020, New York City became the epicenter of the coronavirus disease 2019 (COVID-19) pandemic in the United States. Because healthcare facilities were overwhelmed with patients, the Jacob K. Javits Convention Center was transformed into the nation's largest alternate care site: Javits New York Medical Station (hereafter termed Javits). Protecting healthcare workers (HCWs) during a global shortage of personal protective equipment (PPE) in a nontraditional healthcare setting posed unique challenges. We describe components of the HCW safety program implemented at Javits. SETTING: Javits, a large convention center transformed into a field hospital, with clinical staff from the US Public Health Service Commissioned Corps and the US Department of Defense. METHODS: Key strategies to ensure HCW safety included ensuring 1-way flow of traffic on and off the patient floor, developing a matrix detailing PPE required for each work activity and location, PPE extended use and reuse protocols, personnel training, and monitoring adherence to PPE donning/doffing protocols when entering or exiting the patient floor. Javits staff who reported COVID-19 symptoms were immediately isolated, monitored, and offered a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) test. CONCLUSIONS: A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation's largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses.

Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based immunoassay strategies for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2 and the endemic seasonal human coronaviruses (HCoV), enabling high throughout measurement of pre-existing cross-reactive antibodies. We varied SARS-CoV-2 antigen compositions within the multiplex assay, allowing direct comparisons of the effects of spike protein, receptor-binding domain protein (RBD) and nucleocapsid protein (NP) based SARS-CoV-2 antibody detection. Multiplex immunoassay performance characteristics are antigen-dependent, and sensitivities and specificities range 92-99% and 94-100%, respectively, for human subject samples collected as early as 7-10 days from symptom onset. SARS-CoV-2 spike and RBD had a strong correlative relationship for the detection of IgG. Correlation between detectable IgG reactive with spike and NP also had strong relationship, however, several PCR-positive and spike IgG-positive serum samples were NP IgG-negative. This spike and NP multiplex immunoassay has the potential to be useful for differentiation between vaccination and natural infection induced antibody responses. We also assessed the induction of de novo SARS-CoV-2 IgG cross reactions with SARS-CoV and MERS-CoV spike proteins. Furthermore, multiplex immunoassays that incorporate spike proteins of SARS-CoV-2 and HCoVs will permit investigations into the influence of HCoV antibodies on COVID-19 clinical outcomes and SARS-CoV-2 antibody durability.

Rates, Predictors, and Outcomes of Portal Lymphadenectomy for Resectable Gallbladder Cancer.

INTRODUCTION: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear. PATIENTS AND METHODS: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC. LND performance, predictors of receiving LND, and LND association with overall survival (OS) were assessed. RESULTS: Of 2302 total patients, 1343 (58.3%) underwent LND. Patients who underwent LND were younger and more frequently had private health insurance, a negative surgical margin, higher pathologic T stage, and received adjuvant chemotherapy (all p < 0.001). LND rates were highest at academic centers (70.1%) relative to all other facility types (p < 0.001). LND was independently associated with improved OS [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.44-0.61]. LND was associated with improved OS for pT1b, pT2, and pT3 patients (all p < 0.05) on univariate analysis. LND was independently associated with improved OS in pT2 (HR 0.44, CI 0.35-0.56) and pT3 (HR 0.54, CI 0.43-0.69) patients. CONCLUSIONS: LND is associated with a 48% reduction in risk of death in patients with resectable non-metastatic GBC, with greatest impact in pT2-3 patients. Patients without LND have similar OS to patients with node-positive disease, highlighting the importance of LND. Underutilization of LND likely results in undertreatment of patients with undiagnosed nodal disease, which may contribute to unfavorable oncologic outcomes.

Lymph node sampling in resectable hepatocellular carcinoma: national practice patterns and predictors of positive lymph nodes.

BACKGROUND AND OBJECTIVES: Routine lymphadenectomy (LND) for resectable hepatocellular carcinoma (HCC) remains controversial. We evaluated national LND trends to identify pre-operative factors associated with node-positive disease to determine which patients might benefit from LND. METHODS: We identified HCC patients in the National Cancer Database (NCDB) treated with surgical resection between 2004 and 2015. Demographic, operative, pathologic, and survival data were compared. Multivariable regression was performed to determine preoperative predictors of pathologic nodal disease. RESULTS: Of 8095 total resected patients, 1442 (17.8%) underwent hepatectomy with LND. Patients who received LND had higher preoperative clinical T (T3-T4: 20.0% vs 12.1%, p < 0.001) and N (N1: 3.3% vs 0.6%, p < 0.001) stages. The strongest independent predictor of pathologic nodal disease was clinical N stage (OR 106.54, CI 44.10-257.42). Survival was highest in patients whose surgeons omitted LND or were found with LND to be node-negative on final pathology (p < 0.001). Clinical node positivity had high negative predictive value (97.9%) but moderate positive predictive value (56.3%) in estimating pathologic nodal status. CONCLUSIONS: Defining preoperative clinical nodal status is imperative in HCC patients. Clinical node positivity was the strongest predictor of pathologic nodal disease and its associated worse prognosis. LND can be considered selectively in clinically node-positive patients.

Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer.

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.

An Educational Intervention Reduces Opioids Prescribed Following General Surgery Procedures.

BACKGROUND: Variability exists in opioid prescribing practices among surgeons, frequently resulting in the prescription of excessive opioids. This study evaluated the ability of a single educational intervention targeted toward general surgery residents to reduce the quantity of postoperative opioids prescribed. MATERIALS AND METHODS: This retrospective cohort study evaluated opioid prescribing practices 12 mo prior to and 6 mo following a 30-min lecture for general surgery residents that discussed prescribing guidelines and multimodal analgesia. Opioid volumes (normalized to oral morphine equivalents, OME), opioid type, nonopioid pain medications, and refills requested were analyzed for opioid-naïve adult patients undergoing excisional breast biopsy (EB), mastectomy (M), laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), open umbilical hernia repair (OUHR), open inguinal hernia repair (OIHR), or laparoscopic inguinal hernia repair (LIHR). RESULTS: 695 and 376 patients preintervention and postintervention were included, respectively. Median OME prescribed decreased for EB (150 mg to 75 mg, P < 0.001), M (225 mg to 150 mg, P = 0.85), LA (150 mg to 94 mg, P < 0.001), LC (150 mg to 82 mg, P < 0.001), OUHR (150 mg to 103 mg, P < 0.001), OIHR (175 mg to 100 mg, P = 0.001), and LIHR (200 mg to 113 mg, P < 0.001). Fewer patients received opioids alone and more patients received an opioid with two nonopioid adjuncts (P < 0.001). More patients received oxycodone as fewer received acetaminophen-containing opioid combinations (P < 0.001). Patients requiring refills decreased (11.9% to 7.2%) (P = 0.014). CONCLUSIONS: Following this targeted intervention, patients were discharged with fewer OME and more nonopioid analgesics, even as refill requests decreased. Educating residents on opioid prescription guidelines and multimodal therapy is effective and should be part of the annual didactic curriculum.

Adjuvant Chemotherapy in Resectable Gallbladder Cancer is Underutilized Despite Benefits in Node-Positive Patients.

BACKGROUND: Adjuvant chemotherapy (AC) is recommended following surgical resection of gallbladder cancer regardless of stage. However, stage-specific benefits of AC in gallbladder cancer are unclear. PATIENTS AND METHODS: Patients with resected pathologic stage I-III gallbladder cancer were identified using the 2006-2015 National Cancer Database. Utilization trends, predictors of use, and impact of AC on overall survival (OS) were determined. RESULTS: A total of 5656 patients were included. Use of AC increased from 9.9% in 2006 to 24.2% in 2015 (OR 2.91; 95% CI 2.06-4.09; p < 0.001). However, only 17.5% of patients overall and only 32.4% of node-positive (stage IIIb) patients received AC. Patients receiving AC were younger and had fewer comorbidities, shorter hospitalizations, more advanced disease, and more margin-positive resections (all p < 0.01). Higher pathologic T stage and positive nodal status represented the greatest independent predictors of receipt of AC. While AC demonstrated no OS advantage for stage I patients (p = 0.83), AC was associated with improved OS among stage II patients (p = 0.003), though this impact was not independently associated with improved OS on multivariable analysis. AC was independently associated with improved OS among stage IIIb patients, with a 30% reduction in risk of death (HR 0.70; 95% CI 0.58-0.83; p < 0.001). Younger age, fewer comorbidities, and shorter hospitalization all predicted receipt of AC among stage IIIb patients (all p < 0.05). CONCLUSIONS: Systemic therapy remains underprescribed, in particular among patients that would seem to benefit most. Adjuvant chemotherapy likely improves survival in node-positive gallbladder cancer, but its utility in the treatment of node-negative disease has not been demonstrated.

Chemoprevention in familial adenomatous polyposis: past, present and future.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and temporizing the development of extracolonic disease. An ideal chemoprevention agent should have a biologically plausible mechanism of action, be safe and easily tolerated over a prolonged treatment period, and produce a durable and clinically meaningful effect. To date, no chemoprevention agent tested has fulfilled these criteria. New agents targeting novel pathways in FAP are needed. Substantial preclinical literature exists linking the molecular target of rapamycin (mTOR) pathway to FAP. A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Here, we review the prior literature on chemoprevention in FAP, discuss the rationale for rapamycin in FAP, and outline a proposed clinical trial testing rapamycin as a chemoprevention agent in patients with FAP.

AE37: a HER2-targeted vaccine for the prevention of breast cancer recurrence.

INTRODUCTION: HER2 is a prevalent growth factor in a variety of malignancies, most prominently breast cancer. Over-expression has been correlated with the poorest overall survival and has been the target of successful therapies such as trastuzumab. AE37 is a novel, HER2-directed vaccine based on the AE36 hybrid peptide (aa776-790), which is derived from the intracellular portion of the HER2 protein, and the core portion of the MHC Class II invariant chain (the Ii-Key peptide). This hybrid peptide is given with GM-CSF immunoadjuvant as the AE37 vaccine. AREAS COVERED: This article describes in detail the preclinical science leading to the creation of the AE37 vaccine and examines use of this agent in multiple clinical trials for breast and prostate cancer. The safety profile of AE37 is discussed and opinions on the potential of the vaccine in breast and prostate cancer patient subsets along with other malignancies, are offered. EXPERT OPINION: Future trials utilizing the AE37 vaccine to treat other HER2-expressing malignancies are likely to see similar success, and this will be enhanced by combination immunotherapy. Ii-Key modification of other peptides of interest across oncology and virology could yield impressive results over the longer term.

A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and controls for pre-existing seasonal human coronavirus antibody cross-reactivity.

With growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utilizing serum samples from non-human primate SARS-CoV-2 infection models, an archived human sera bank and subjects enrolled at five U.S. military hospitals. The MMIA incorporates prefusion stabilized spike glycoprotein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human coronaviruses HCoV-HKU1 and HCoV-OC43, into a multiplexing system that enables simultaneous measurement of off-target pre-existing cross-reactive antibodies. We report the sensitivity and specificity performances for this assay strategy at 98% sensitivity and 100% specificity for subject samples collected as early as 10 days after the onset of symptoms. In archival sera collected prior to 2019 and serum samples from subjects PCR negative for SARS-CoV-2, we detected seroprevalence of 72% and 98% for HCoV-HKU1 and HCoV-0C43, respectively. Requiring only 1.25 µL of sera, this approach permitted the simultaneous identification of SARS-CoV-2 seroconversion and polyclonal SARS-CoV-2 IgG antibody responses to SARS-CoV-1 and MERS-CoV, further demonstrating the presence of conserved epitopes in the spike glycoprotein of zoonotic betacoronaviruses. Application of this serology assay in observational studies with serum samples collected from subjects before and after SARS-CoV-2 infection will permit an investigation of the influences of HCoV-induced antibodies on COVID-19 clinical outcomes.

Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence.

PURPOSE: AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. METHODS: In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. RESULTS: 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275-1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499-1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114-1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142-0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. CONCLUSIONS: This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.

Results of a Randomized Phase IIb Trial of Nelipepimut-S + Trastuzumab versus Trastuzumab to Prevent Recurrences in Patients with High-Risk HER2 Low-Expressing Breast Cancer.

PURPOSE: Preclinical data provide evidence for synergism between HER2-targeted peptide vaccines and trastuzumab. The efficacy of this combination was evaluated in patients with HER2 low-expressing breast cancer in the adjuvant setting. PATIENTS AND METHODS: A phase IIb, multicenter, randomized, single-blinded, controlled trial enrolled disease-free patients after standard therapy completion (NCT01570036). Eligible patients were HLA-A2, A3, A24, and/or A26+, and had HER2 IHC 1+/2+, FISH nonamplified breast cancer, that was node positive and/or hormone receptor-negative [triple-negative breast cancer (TNBC)]. Patients received trastuzumab for 1 year and were randomized to placebo (GM-CSF, control) or nelipepimut-S (NPS) with GM-CSF. Primary outcome was 24-month disease-free survival (DFS). Secondary outcomes were 36-month DFS, safety, and immunologic response. RESULTS: Overall, 275 patients were randomized; 136 received NPS with GM-CSF, and 139 received placebo with GM-CSF. There were no clinicopathologic differences between groups. Concurrent trastuzumab and NPS with GM-CSF was safe with no additional overall or cardiac toxicity compared with control. At median follow-up of 25.7 (interquartile range, 18.4-32.7) months, estimated DFS did not significantly differ between NPS and control [HR, 0.62; 95% confidence interval (CI), 0.31-1.25; P = 0.18]. In a planned exploratory analysis of patients with TNBC, DFS was improved for NPS versus control (HR, 0.26; 95% CI, 0.08-0.81, P = 0.01). CONCLUSIONS: The combination of NPS with trastuzumab is safe. In HER2 low-expressing breast cancer, no significant difference in DFS was seen in the intention-to-treat analysis; however, significant clinical benefit was seen in patients with TNBC. These findings warrant further investigation in a phase III randomized trial.

Initial safety analysis of a randomized phase II trial of nelipepimut-S + GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors.

The development of HER2-targeted therapy has decreased recurrence rates and improved survival, transforming the natural history of HER2-positive breast cancer. However only a minority of breast cancer patients benefit as these agents are not used in patients with tumors expressing low levels of HER2. Preclinical data suggests a synergistic action of HER2-targeted vaccination with trastuzumab. We report the initial safety interim analysis of a phase II trial that enrolled patients with HER2 low-expressing (IHC 1+/2+) breast cancer who were clinically disease-free after standard therapy. Patients were randomized to receive the HER2-peptide vaccine nelipepimut-S + GM-CSF with trastuzumab (vaccine arm) or trastuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analysis that occurred after enrollment of 150 patients showed no significant differences in toxicity between the two arms, including cardiac toxicity. The clinical efficacy of this combination will be reported 6 months after the final patient was enrolled.

Effects of HLA status and HER2 status on outcomes in breast cancer patients at risk for recurrence - Implications for vaccine trial design.

Immunotherapy, using peptide-based cancer vaccines is being studied to assess its potential in breast cancer. Trials of HLA-restricted peptide vaccines have been difficult to enroll given HLA subtype restrictions. It is necessary to determine the prognostic significance of HLA-status in breast cancer if patients who are ineligible to receive a vaccine due to their HLA-status are used as controls. The impact of targeted tumor associated antigen expression, when it effects eligibility is also important. We examined control patients from two randomized phase II trials that tested HER2-peptide vaccines to determine the effect of HLA-A2 status and HER2 expression on disease-free survival. The analysis showed that HLA-A2-status does not affect disease-free survival, regardless of HER2 expression suggesting that HLA-A2 negative patients can be used as control patients. Additionally, HER2 over-expression was associated with a better disease-free survival in this population, underscoring the need for additional therapies in HER2 low-expressing breast cancer. ClinicalTrials.gov Identifier: NCT00524277.

Results of a Phase Ib Trial of Combination Immunotherapy with a CD8+ T Cell Eliciting Vaccine and Trastuzumab in Breast Cancer Patients.

BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Patients received 6-monthly inoculations of GP2+ granulocyte-macrophage colony-stimulating factor (GM-CSF) administered concurrently with standard-of-care trastuzumab. Local and systemic toxicity, as well as left ventricular ejection fraction (LVEF) were monitored. Immunologic responses were assessed in vivo by measuring the local reaction and in vitro using an interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assay. RESULTS: Seventeen disease-free breast cancer patients were vaccinated. There were no dose-limiting or grade 3-5 local or systemic toxicities, and the median LVEF was unchanged from baseline after vaccination. Mean local reaction at initial inoculation was 28 ± 10 mm, increasing to 68 ± 8 mm at the final inoculation (p < 0.01). Mean ELISPOT response to GP2 increased from 47 ± 19 at baseline to 144 ± 60 (p = 0.13) after vaccination. Based on safety and immunologic data, the appropriate dose was determined to be 1000 µg of GP2 + 250 µg of GM-CSF. CONCLUSION: The GP2 + GM-CSF vaccine is safe and stimulates an immunologic response when administered concurrently with trastuzumab. An ongoing phase II trial is evaluating the efficacy of combining a CD8 T-cell-eliciting vaccine with trastuzumab in HER2-positive breast cancer patients.

Peptide-Based Cancer Vaccine Strategies and Clinical Results.

Active cancer immunotherapy is an exciting and developing field in oncology research. Peptide vaccines, the use of isolated immunogenic tumor-associated antigen (TAA) epitopes to generate an anticancer immune response, are an attractive option as they are easily produced and administered with minimal toxicity. Multiple TAA-derived peptides have been identified and evaluated with various vaccine strategies currently in clinical testing. Research suggests that utilizing vaccines in patients with minimal-residual disease may be a more effective strategy compared to targeting patients with widely metastatic disease as it avoids the immune suppression and tolerance associated with higher volumes of more established disease. Clinical trials also suggest that vaccines may need to be tailored and administered to specific cancer subtypes to achieve maximum efficacy. Additionally, numerous immunomodulators now in research and development show potential synergy with peptide vaccines. Our group has focused on a simpler, single-peptide strategy largely from the HER2/neu protein. We will discuss our experience thus far as well as review other peptide vaccine strategies that have shown clinical efficacy.

Hand-sewn gastrojejunostomy using knotless unidirectional barbed absorbable suture during laparoscopic gastric bypass.

BACKGROUND: This report describes the authors' institutional experience using knotless unidirectional barbed absorbable suture to close the common enterotomy of the jejunojejunostomy (JJ) and to create a hand-sewn gastrojejunostomy (GJ) during laparoscopic Roux-en-Y gastric bypass. METHODS: A retrospective review of morbidly obese patients who underwent laparoscopic gastric bypass with a hand-sewn GJ between April 2011 and 2012 was performed. The authors' traditional technique (TT) consisted of using standard monofilament absorbable suture to close the common JJ enterotomy in a single running layer and to create the GJ with a two-layer anastomosis. A novel technique (NT) was introduced using knotless unidirectional barbed monofilament absorbable suture to perform both tasks. A comparison between these two techniques was performed. RESULTS: In this study, 84 patients with a mean body mass index of 41.7 ± 4.7 kg/m(2) underwent laparoscopic gastric bypass using a hand-sewn technique. For the 84 patients, 75 primary procedures (89.3 %) and 9 revisional procedures (10.7 %) were performed. In 38 procedures (45.2 %), the TT was used, whereas 46 cases (54.8 %) were managed using the NT. For the primary procedures, the average operating room times were slightly faster in the NT group (178.9 ± 44.4 vs 154.2 ± 74.7 min; p = 0.08). The average hospital length of stay was comparable between the two groups (2.3 ± 0.7 vs 2.6 ± 1.4 days; p = 0.25). A 30-day follow-up assessment was obtained for all 84 patients, without a significant difference in the overall complication rate between the two groups (TT 18.4 % vs NT 13 %; p = 0.77). No complications were secondary to the JJ closure or gastrojejunostomy. The complications included bleeding (n = 1), small bowel obstruction (n = 1), dehydration (n = 2), esophagitis (n = 1), and subarachnoid hemorrhage (n = 1). No anastomotic leak or stenosis occurred in either group. The mean percentage of excess weight loss at 1 month was 21.3 % ± 5.4 %, without a significant difference between the two groups. CONCLUSION: In the study cohort, the use of knotless unidirectional barbed suture instead of traditional monofilament absorbable suture had similar 30-day outcomes and appears to be a feasible option for laparoscopic bowel closure and anastomosis creation.

Cancer vaccines: should we be targeting patients with less aggressive disease?

There is enthusiasm for using vaccines to stimulate the immune system to treat cancer. In this article, the authors review the evolution of vaccines evaluated in clinical trials, starting with Phase III trials in metastatic disease and progressing to trials in the adjuvant setting. Data from these trials suggest that cancer vaccines may be more effective in patients with lower volume disease, and data from the E75 peptide vaccine trials suggest that vaccines may be most effective in less aggressive disease.

The GP2 peptide: a HER2/neu-based breast cancer vaccine.

Preclinical studies suggest that GP2, a HER2/neu-derived peptide, is immunogenic. Subsequent phase I clinical trials demonstrated that GP2-based vaccines are safe and effective in stimulating peptide-specific immunity. A GP2 peptide vaccine is currently being evaluated in a phase II efficacy trial enrolling breast cancer patients. This article reviews initial studies characterizing GP2, clinical trials investigating GP2-based vaccines, and novel immunotherapy strategies incorporating GP2 in combination with other peptides or with the monoclonal antibody trastuzumab.

Breast cancer vaccines: ongoing National Cancer Institute-registered clinical trials.

Advances in the molecular characterization of human tumors have led to increased interest in the development of targeted therapeutics to include cancer vaccines. The recent success of sipuleucel-T, an autologous cellular vaccine administered to patients with hormone-refractory metastatic prostate cancer, suggests that this is a viable therapeutic option in the management of patients with solid tumors. This article focuses on breast cancer vaccines emphasizing delivery platforms, target antigens and novel strategies designed to enhance response to vaccination that are being evaluated in ongoing Phase II clinical trials.