Battlefield Acupuncture vs Ketorolac for Treating Pain in the Emergency Department.

Background: Many patients arrive in the emergency department (ED) with acute pain. Battlefield acupuncture (BFA) uses small, semipermanent acupuncture needles in 5 set points anatomically located on each ear to reduce pain in a few minutes. Pain relief can last months, depending on the pathology of the pain. At the Jesse Brown Veterans Affairs Medical Center (JBVAMC) ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain. In 2018, BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness in pain reduction vs ketorolac has not been evaluated in this patient population. The objective of this study was to determine whether BFA monotherapy was noninferior to ketorolac 15 mg for reducing pain scores in the ED. Methods: This study was a retrospective, electronic chart review of patients who presented to JBVAMC ED with acute pain or acute-on-chronic pain and received ketorolac or BFA. The primary endpoint was the mean difference in the numeric rating scale (NRS) pain score from baseline. Secondary endpoints included the number of patients receiving pain medications, including topical analgesics, at discharge and treatment-related adverse events in the ED. Results: A total of 61 patients were included in the study. Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was higher in the BFA group (8.7 vs 7.7; P = .02). The mean difference in NRS pain scores from baseline to post-intervention was 3.9 for the BFA group and 5.1 for the ketorolac group. The difference in reducing the NRS pain score between the intervention groups was not statistically significant. No adverse events were observed in either treatment group. Conclusions: For treating acute and acute-on-chronic pain in the ED, BFA did not differ compared with ketorolac 15 mg in NRS pain score reduction. This study's results add to the limited existing literature suggesting that both interventions could result in clinically significant reductions in pain scores for patients presenting to the ED with severe and very severe pain, indicating BFA could be a viable nonpharmacologic treatment option.

Intrathecal Morphine and Effect on Opioid Consumption and Functional Recovery after Pancreaticoduodenectomy.

BACKGROUND: Single-shot intrathecal morphine (ITM) is an effective strategy for postoperative analgesia, but there are limited data on its safety, efficacy, and relationship with functional recovery among patients undergoing pancreaticoduodenectomy. STUDY DESIGN: This was a retrospective review of patients undergoing pancreaticoduodenectomy from 2014 to 2020 as identified by the institutional NSQIP Hepato-pancreato-biliary database. Patients were categorized by having received no spinal analgesia, ITM, or ITM with transversus abdominus plane block (ITM+TAP). The primary outcomes were average daily pain scores from postoperative days (POD) 0 to 3, total morphine equivalents (MEQ) consumed over POD 0 to 3, and average daily inpatient MEQ from POD 4 to discharge. Secondary outcomes included the incidence of opioid related complications, length of stay, and functional recovery. RESULTS: A total of 233 patients with a median age of 67 years were included. Of these, 36.5% received no spinal analgesia, 49.3% received ITM, and 14.2% received ITM+TAP. Average pain scores in POD 0 to 3 were similar by mode of spinal analgesia (none [2.8], ITM [2.6], ITM+TAP [2.3]). Total MEQ consumed from POD 0 to 3 were lower for patients who received ITM (121 mg) and ITM+TAP (132 mg), compared with no spinal analgesia (232 mg) (p < 0.0001). Average daily MEQ consumption from POD 4 to discharge was lower for ITM (18 mg) and ITM+TAP (13.1 mg) cohorts compared with no spinal analgesia (32.9 mg) (p = 0.0016). Days to functional recovery and length of stay were significantly reduced for ITM and ITM+TAP compared with no spinal analgesia. These findings remained consistent through multivariate analysis, and there were no differences in opioid-related complications among cohorts. CONCLUSIONS: ITM was associated with reduced early postoperative and total inpatient opioid utilization, days to functional recovery, and length of stay among patients undergoing pancreaticoduodenectomy. ITM is a safe and effective form of perioperative analgesia that may benefit patients undergoing pancreaticoduodenectomy.

Early postoperative ERAS compliance predicts decreased length of stay and complications following liver resection.

BACKGROUND: Enhanced recovery after surgery (ERAS) components for liver resection lack standardization and compliance. We evaluated our ERAS protocol and describe the association of postoperative ERAS compliance with length of stay (LOS) and complications. METHODS: We retrospectively reviewed patients undergoing liver resection at our institution from 2016 to 2020. Pre- and post-ERAS outcomes and compliance at 72 h were compared with LOS and complications. LOS beyond 72 h was defined as LOS72. RESULTS: 210 patients were included. Post-ERAS patients had significantly shorter LOS (5.1 vs. 7.3 days, p = 0.0014) with no difference in 30-day mortality, morbidity, or readmissions. ERAS components associated with shorter LOS72 were regular diet (HR 1.73), fluid discontinuation (HR 1.63), drain removal (HR 1.94), multimodal and oral analgesia (HR 1.51), and ambulation >100 ft (HR 2.23). LOS72 was 1-day for ≥9 ERAS component compliance, 4-days for 6-8 components, and 6-days for <6 components. 30-day complication rates for patients with ≥9 components by postoperative day 3 (POD3) were significantly lower than those with 6-8 (12 vs 32%). CONCLUSION: ERAS decreases LOS after liver resection. Nutritional advancement, drain discontinuation, multimodal and oral analgesia, and ambulation >100 ft by POD3 are associated with decreased LOS72. Achieving ≥6 components by POD3 predicts decreased LOS72 and complications.

Picomets: Assessing single and few cell metastases in melanoma sentinel lymph node biopsies.

BACKGROUND: Lymph node involvement is a significant prognostic factor for melanoma. Both number of positive nodes and disease burden within a lymph node affects survival. However, the significance of few tumor cells within a single node and subsequent optimal management remains without consensus. We investigated the implications of minimal nodal disease on clinical outcomes. METHODS: We reviewed 752 patients who underwent lymph node sampling at time of primary melanoma resection at our institution over 15 years. We deemed patients who had 1 node with 1 to 4 atypical cells staining positive for either Melan-A or Sox-10 as having "picomets." We examined the initial clinicopathological features, subsequent management, and outcomes. RESULTS: Thirty-three patients (4%) met criteria for having picomets. The most common number of positively staining atypical cells was 1 (n = 13). Nodal staging at initial pathology review varied, and overall stage ranged from IA to IIIC. Four patients underwent further therapy, none of whom had recurrent disease. Of the 29 patients undergoing observation/surveillance only, 5 had disease recurrence (17%). CONCLUSION: Although patients with picomets had better outcomes than historical stage matched cohorts, a small subset had recurrent disease. Staging patients with picomets as "N0" may not reflect the true negative prognostic significance of picomets. A larger population of patients meeting picomets criteria is needed to draw further conclusions.

Drugs to Be Used With a Filter for Preparation and/or Administration-2019.

This chart is an update to the 2012 article published in Hospital Pharmacy on injectable drugs to be used with a filter. To update the chart, drugs approved from December 2011 to April 2019 were reviewed to determine if they require filtration and drugs included in the 2012 table were reviewed for accuracy. Readers are urged to review national standards of practice for information about clinical situations that warrant the use of a filter for medication preparation or administration, independent of the drug being given, and the reader should consult the Food and Drug Administration (FDA)-approved prescribing information for the most up-to-date information.

Early Prediction of Length of Stay After Pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is an evidence-based clinical pathway designed to standardize and optimize care. We studied the impact of ERAS and sought to identify the most important recommendations to predict shorter length of stay (LOS) after pancreaticoduodenectomy (PD). METHODS: We retrospectively reviewed all patients undergoing PD at our institution between January 2014 and June 2018. We compared clinicopathologic outcomes for patients before and after ERAS implementation. We defined "A-recommendations" as those that were graded "strong" and had "moderate" or "high" levels of evidence. We then compared outcomes of the ERAS group with adherence to "A-recommendations" and performed a subset analysis of "A-recommendations" over the first 72 h after surgery, which we termed "early factors". RESULTS: A total of 191 patients underwent PD during the study period. We excluded 87 patients who had minimally invasive PD (22), vascular reconstruction (53), or both (12). Of the 104 patients studied, 56 (54%) were pre-ERAS and 48 (46%) were ERAS. There were no differences in comorbidities or demographics between these groups, and morbidity, mortality, and readmission rates were also similar (P > 0.6). Median LOS was 3.5 d shorter in the ERAS group (7 versus 10.5 d, P < 0.001). Adherence to "A-recommendations" within ERAS was associated with a decreased LOS (r = -0.52 P = 0.0001). Patients with >5 "early factors" had a median LOS of 6 d, whereas patients with <5 "early factors" had a median LOS of 9 d (P = 0.008). CONCLUSIONS: ERAS is an effective protocol that standardizes care and reduces LOS after PD. Implementation of ERAS resulted in a 3.5-day reduction in our LOS with no change in morbidity, mortality, or readmissions. Adherence to ERAS protocol "A-recommendations" and ≥5 "early factors" may be predictive of shortened LOS.

Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1-Resistant Tumors Leading to Tumor Eradication.

Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T-cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the "exhaustion" markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD-1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. Cancer Immunol Res; 5(2); 127-36. ©2017 AACR.

Surgical readmissions: results of integrating pre-, peri- and postsurgical care.

AIMS: To explore the feasibility of recruiting surgical oncology patients and implementing a surgical integrated discharge (SID) programme led by advanced practice providers (APP). BACKGROUND: Burden of illness and complexity of treatment regimen makes it challenging for surgical oncology patients to participate in research. Surgical oncology nurses may have the necessary expertise to overcome this problem. DESIGN: Controlled longitudinal prospective observational study. METHODS: The SID programme included multidisciplinary care coordination, regular communication among APPs and proactive postdischarge follow-up. Administrative databases were used to identify matching historical controls (n = 113) and evaluate programme outcomes. RESULTS: Patient enrolment was 84%. The main challenges for the programme implementation included incompatible health information systems among care settings, variation in care processes among hospital units and need for provider behaviour change. CONCLUSIONS: Most surgical oncology patients are willing to participate in outcomes programmes when contacted by familiar clinical personnel but programme implementation requires leadership support, communication among care teams and training and infrastructure.

The influence of staple size on fistula formation following distal pancreatectomy.

BACKGROUND: Pancreatic fistula continues to be a source of significant morbidity following distal pancreatic resections. The technique of pancreatic division varies widely among surgeons, and there is no evidence that identifies a single method as superior. In our practice, the technique of distal pancreatic resection has evolved from cut-and-sew to stapled technique with green and recently white cartridge. The aim of our study was to evaluate the rate of clinically significant fistulas [International Study Group on Pancreatic Fistula (ISGPF) grade B or C] following distal pancreatectomy and to identify variables associated with a low rate of fistula development. METHODS: Clinical records of all patients who underwent distal pancreatic resections between February 1999 and July 2010 by a single surgeon were retrospectively reviewed focusing on the incidence and type of pancreatic fistula as defined by ISGPF. Study variables included age, gender, surgical approach, extent of resection, ASA classification, type of stapler cartridge, use of Seamguard™, and ISGPF classification. Statistical analysis was performed using Fisher's exact test, and univariate and multivariate logistic regression. RESULTS: Sixty-four patients (median age 60, range 21-85; 54% male) underwent distal pancreatic resection (laparoscopy 50% vs. open 50%). The most common indications were pancreatic adenocarcinoma (N = 15; 23%) and neuroendocrine neoplasms (N = 14; 22%). Clinically significant pancreatic fistula developed in 24% (N = 15). The rate of fistula with cut-and-sew technique was 36% (4/11), with stapled green cartridge 31% (9/29) and only 5% (1/21) with stapled vascular cartridge. Univariate logistic regression identified vascular cartridge size (p = 0.04, OR 0.11) and open stapled technique (p = 0.05, OR 0.12) as variables significantly associated with a low fistula rate. Both vascular cartridge size (p = 0.05, OR 0.10) and open stapled technique (p = 0.04, OR 0.08) remained significant when analyzed by multivariate logistic regression. Division of pancreatic parenchyma with vascular cartridges resulted in significantly (p = 0.03, OR 9.0) lower fistula rate compared to green cartridges. The use of Seamguard™ did not affect fistula rate (16% vs. 27%; p = 0.34) nor did the performance of multivisceral resection vs. distal pancreatectomy/splenectomy alone (21% vs. 23%, p = 1.0). CONCLUSION: The optimal technique of pancreatic division has not been conclusively established. Dividing the pancreas utilizing vascular (2.5 mm) staple cartridges significantly decreased the rate of clinically significant pancreatic fistula and we have changed our practice accordingly. A prospective randomized trial is necessary to validate these results.

Molecular mechanisms of cholangiocarcinogenesis: are biliary intraepithelial neoplasia and intraductal papillary neoplasms of the bile duct precursors to cholangiocarcinoma?

Cholangiocarcinoma (CC) is a rare, malignant neoplasm that can develop from any site within the intrahepatic or extrahepatic biliary tree. Although the key steps of cholangiocarcinogenesis remain unknown, it has been hypothesized that CC may develop through two key premalignant precursor lesions: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB). These lesions probably are analogous to pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm, respectively. This article outlines the molecular basis of cholangiocarcinogenesis through the BilIN and IPNB pathways. It highlights the genetic mutations that alter cellular proliferation, tumor suppression, and impairment of critical mucinous, cell-adhesion, and matrix proteins.

Stat6(null phenotype) human lymphocytes exhibit increased apoptosis.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered apoptosis and increased levels of Th1 cytokines (IL-12, TNF-alpha, and IFN-gamma). These proinflammatory events may result from dysfunctional IL-4/Stat6 signal transduction that normally promotes Th2 lymphocyte differentiation and consequential down-regulation of the immune response. The goal of the present study was to measure apoptosis, levels of relevant cytokines, and the effects of cytokine manipulation on apoptosis in cell lines derived from IBD patients that express dysfunctional Stat6 (Stat6(null phenotype)) and wild-type Stat6 (Stat6(high phenotype)). MATERIALS AND METHODS: Lymphocytes with Stat6(null phenotype) (n = 5) or wild-type (n = 5) status were cultured with and without the addition of exogenous cytokines or neutralizing antibodies (IL-12, TNF-alpha, and IFN-gamma). Apoptosis was determined by flow cytometry using Annexin V-PE dual staining. Cytokine levels were determined by ELISA. RESULTS: Stat6(null phenotype) cells exhibited increased apoptosis compared with wild-type cell lines (13.3% +/- 2.9 versus 4.5% +/- 0.4, P < 0.0001). Four of five Stat6(null phenotype) cell lines expressed 5- to 10-fold elevations in IL-12 and IFN-gamma. Addition of exogenous cytokines or neutralizing antibodies had no effect on apoptosis. CONCLUSIONS: Apoptotic cell death is elevated in Stat6(null phenotype) cell lines suggesting a role for Stat6 in apoptosis regulation, a previously unrecognized observation. Increased levels of IL-12 and IFN-gamma were found in the Stat6(null phenotype) cell lines; however, the apoptosis observed is not the consequence of increased IL-12, IFN-gamma, or TNF-alpha. Stat6(null phenotype) cell lines exhibit variably increased levels of these Th1 cytokines, consistent with their human source, and may be a valid source for investigations into IBD pathophysiology.

Human B lymphoblast cell lines defective of Stat6 signaling produce high levels of proinflammatory cytokines IL-12, TNFalpha and IFNgamma.

Based on Stat6 gene knockout animal models, the Stat6 signaling pathway has been suggested to play a role in carcinogenesis and Th1/Th2 cytokine balance. Using a semiquantitative EMSA assay and EBV-transformed human B lymphoblast cell lines, we have previously identified three Stat6 activational phenotypes, termed as Stat6high, Stat6low, and Stat6null. A genetic mechanism has been proposed which determines the IL-4-induced activation of the human Stat6 signaling. With respect to the contribution of variant phenotypes to human disease, we further hypothesize that the Stat6null phenotype may result from a partial defect in Stat6 signaling which resembles Stat6 knockout animals in several functional aspects. The characterization of the human Stat6null phenotype stably displayed by the EBV-B cell lines is easily assailable and possesses important implications with respect to Th1/Th2 cytokine imbalance in diseases such as cancer development/metastasis and inflammatory diseases. In this study, we have extended our investigation to the downstream regulatory consequences associated with these Stat6 phenotypes. Production of three important proinflammatory cytokines, IL-12, TNFalpha and IFNgamma was examined in spontaneous EBV-B cell culture using ELISA methodology. Individual cell lines defined as Stat6null produced significantly higher levels of IL-12, TNFalpha and IFNgamma on day 4 in spontaneous culture in comparison with cell lines characterized as Stat6high and Stat6low. These observations of the human Stat6null phenotype, together with those accruing from Stat6 knockout mouse model studies, suggest that the Stat6 signaling pathway may play a role in maintaining the Th1/Th2 cytokine balance by directly and indirectly down-regulating the production of proinflammatory cytokines, a regulatory process which appears to go awry in inflammatory diseases. Moreover, observations from signal transduction studies in our human B lymphocyte model may be compatible with those in the chosen mouse B lymphocyte for establishing signaling networks by the Alliance for Cellular Signaling (AfCS).