Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

A review of force and resonance sensors used in the clinical study of tissue properties.

Tactile sensing is commonly carried out by humans using their fingers or hands to estimate the physical properties of an object. A large body of literature covers a range of applications of these methods in clinical situations. The objective of this work is to show the breadth of application areas explored and the achievements that have been made in the measurement of physical variables of interest to physicians using tactile force and resonance sensors. Although a broad spectrum of applications has been considered, of particular interest is the application of these methods to determine tissue properties in vivo. Progress in this direction has been made by various groups particularly with respect to piezoelectric and capacitance sensors. Also described are the findings of a preliminary study of a tactile system designed to examine the abdomen of the clinically super-obese patient.

Modified map-seeking circuit: use of computer-aided detection in locating postoperative retained foreign bodies.

BACKGROUND: More than 98% of intra-operative X-rays taken to search for postoperative retained foreign bodies (RFBs) have negative findings; in over 30% of cases of such X-rays, the finding is a false negative. Newer technologies created to find RFBs must not only reduce the false-negative rate, but also must not increase the burden of detecting RFBs. We have introduced the use of computer-aided detection (CAD) to facilitate the detection of RFBs on X-rays utilizing a modified version of map-seeking circuit (MSC) algorithm the referenced map-seeking circuit (RMSC), for our proof-of-concept study for detection of needles in plain abdominal X-rays. METHODS: Images were obtained by using a portable cassette-based X-ray machine and a C-arm (digital) machine, both of which are commonly used in the operating room. The images obtained using these machines were divided into subimages of approximately 250 × 250 pixels each, for a total of 455 subimages from the cassette-based machine (A) and 365 from the digital machine (B) for use as test samples. Images obtained from A and B were analyzed separately using our modified MSC algorithm with a minimum (τ = 0) and a maximum threshold (τ = 0.5). RESULTS: The automated detection rate (positive predictive value) was 86%, with a false positive/negative rate of 10% to 15% when τ was zero. CONCLUSION: The CAD-based RMSC algorithm has the potential to improve the accuracy with which RFBs can be found in X-rays. Further research is needed to optimize the detection rate and to identify a wider range of RFBs.

Contamination of equipment in emergency settings: an exploratory study with a targeted automated intervention.

BACKGROUND: Despite standard manual decontamination, hospital equipment remains contaminated with microorganisms, contributing to nosocomial transmission and hospital acquired infections. This has the potential to negate the effects of healthcare workers' hand-washing protocols. In order to decrease the likelihood of equipment contamination, there has been a rise in the use of disposable pieces of equipment, especially non-critical disposables. However, these carry a significant cost, both a direct financial cost (running into billions of dollars), as well as a cost to the environment. This is important because we hope to contain the cost of healthcare, one way to do that, is to look to the hospitals themselves, for innovative solutions that maintain the standard of care. OBJECTIVE: To develop and evaluate the effectiveness of an simple decontamination device for use with portable hospital equipment, by comparing rates of residual contamination after use of the novel device versus those seen with standard manual decontamination methods. METHODS: The Self-cleaning Unit for the Decontamination of Small instruments (SUDS) is a user-friendly, automated instrument developed via multi-disciplinary collaboration for decontamination in the clinical area. Pre- and post- utilization of portable medical equipment in an emergency department (ED) setting were cultured. To evaluate durability of the decrease in antimicrobial contamination, objects were re-cultured 48 hours after SUDS cleaning and following re-introduction into the clinical setting. RESULTS: After manual decontamination, 25% (23/91) of the tested objects in the ED were found to be culture positive with clinically significant microorganisms(CSO). Fifteen percent (ED) of non-critical equipment tested had multiple organisms. Following the use of SUDS, the colonization rate decreased to 0%. Following SUDS treatment and re-introduction into the clinical settings, after 48 hours the contamination rates as reflected by the cultures remained 0%. CONCLUSION: Standard non-critical equipment is contaminated with clinically significant microorganisms. The SUDS device allows for effective and durable decontamination of hospital equipment of varying sizes in the clinical area without disrupting patient care.

Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph nodes and lymph node ratio.

BACKGROUND: There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant 5-flurouracil-based chemoradiation therapy. METHODS AND MATERIALS: Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available. RESULTS: At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration [HR] 2.39) and presence of metastatic lymph nodes (HR 1.89, both p < 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all p < 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR >or=0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%; p < 0.05). CONCLUSIONS: Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes.

For the surgeon: an introduction to nanotechnology.

BACKGROUND: The study and application of nanoparticles is advancing rapidly within medicine and surgery. In this article, we review nanotechnology with a view as to its impact on surgery. We also review potential toxicity, current regulations, and ethical considerations. DATA SOURCES: A Medline review of nanotechnology and nanosurgery was performed. Important publications in the history of the science and demonstrated important concepts were selected for review. CONCLUSION: Nanotechnology is a relatively new but fast evolving field. Its potential impact on medicine and surgery is expanding in areas from drug delivery to rudimentary nanosurgery at the cellular level. This review is written to give the surgeon an overview of the field particularly in reference to its potential surgical applications.

Post discharge prophylactic anticoagulation in gastric bypass patient-how safe?

BACKGROUND: It is becoming an increasingly common practice to discharge gastric bypass (GBP) patients on prophylactic anticoagulation. This is because pulmonary embolism (PE) is a common cause of mortality postoperatively. This study was undertaken to: (1) determine the incidence of major bleeding in GBP patients discharged on prophylactic low molecular weight heparin (LMWH)-enoxaparin and, (2) correlate the bleeding risk to the dose used. METHODS: Retrospective chart review of all open GBP operation from June 2004 to August 2005. One hundred and twenty seven patients were sent home on LMWH for 2 weeks. INDICATIONS: Body mass index (BMI) > or =50 kg/m(2) with chronic venous stasis and/or obstructive sleep apnea, previous history of PE or deep vein thrombosis (DVT) or BMI > or =60 kg/m(2). The study group was divided into two subgroups: 40 mg twice daily (bid) and 60 mg bid LMWH. Statistical analysis was done with the chi-square. The primary outcome measure was major bleeding; defined as bleeding during the period of LMWH use associated with symptomatic decrease in hematocrit (HCT), necessitating stopping LMWH administration before the end of the study period (2 weeks), bleeding-related readmission, blood transfusion, or intervention. Excluded were patients on warfarin or treated with therapeutic LMWH. RESULTS: The groups were similarly matched for age, body mass index, and risk factors. No episode of major bleeding after discharge occurred in either group. CONCLUSION: The use of low molecular weight heparin for prophylactic anticoagulation after open gastric bypass is not associated with risk of major bleeding.

Operative mortality after hepatic resection: are literature-based rates broadly applicable?

INTRODUCTION: Literature-based data on mortality after hepatectomy may be misleading, as poor outcomes are less likely to be published. The objective of the current study was to compare published vs public, nationally available mortality rates after hepatic resection. MATERIALS AND METHODS: A systematic MEDLINE review was conducted to identify reports of hepatectomy outcome between January 1998-December 2004. Data were analyzed to calculate literature-based mortality rate and then compared with population-based mortality rate for hepatectomy using the Nationwide Inpatient Sample (NIS) dataset. RESULTS: Twenty-three publications fulfilled screening criteria. The studies included 7,073 patients who had undergone hepatic resection (46.1% within USA vs 53.9% outside USA). Most patients were male (58.6%) with median age of 56 years. Indications for hepatic resection included hepatocellular carcinoma (47.7%), metastatic disease (34.3%), or other (18.1%). Cirrhosis was present in 23.2% of patients; 46.9% patients underwent either a hemi-hepatectomy or extended resection. The literature-based mortality rate was 3.6% (US centers only, 2.8%). Analysis of NIS revealed 11,429 hepatectomy cases. After controlling for gender, age, extent of hepatectomy, hepatocellular cancer diagnosis, and presence of cirrhosis, the adjusted NIS-based perioperative mortality rate for hepatectomy was 5.6% (95% CI, 5.0-6.2%). The relative mortality after hepatectomy was 1.6-fold higher based on population-based data compared with reports from the literature (P<0.05). CONCLUSION: Actual population-based mortality rates for major liver resections may be higher than those reported in the literature. Informed consent should reflect actual local and national mortality rates rather than selective reports from the literature.

Malakoplakia occurring in association with colon carcinoma.

Malakoplakia, characterized by histiocytes with Michaelis-Gutmann bodies, is a rare entity. It is particularly so in the gastrointestinal tract, where it has been described in association with colon cancer, with about 20 cases described worldwide. The significance of this condition lies in its potential effect upon the preoperative staging and treatment of associated colorectal cancer. Its presence may lead to preoperative clinical and radiological over staging and more extensive resection, as well as the use of neoadjuvant therapy or a decision to undertake palliative care. This condition is more common in males. We present the case of the oldest reported patient with this association. The patient was a 90-year-old female who was treated with a sigmoid resection for an obstructing sigmoid lesion. At operation, the left ureter was embedded within an inflammatory pericolic mass but was not grossly involved with tumor. The tumor was a Dukes' stage B adenocarcinoma and occurred in association with malakoplakia.

Tumor-to-tumor metastasis to a thyroid follicular adenoma as the initial presentation of a colonic adenocarcinoma.

The incidence of thyroid involvement by metastatic disease from distant organs ranges from an average of 3.1% in surgical series to 5.3% in autopsy series. However, the metastasis of one tumor into another (traditionally referred to as 'tumor-to-tumor metastasis') is distinctly uncommon. Typically, they are identified as new manifestations or necropsy findings of a known, pre-existing donor tumor. Herein is described the case of a 59-year-old woman whose thyroid nodule (a follicular adenoma) was resected and found to contain foci of a well-differentiated adenocarcinoma with a morphologic and immunohistochemical profile consistent with origination from the lower gastrointestinal tract. Subsequent diagnostic work-up revealed a sigmoid colon tumor with metastases to the liver. This is, to the authors' knowledge, the first reported example of a colon adenocarcinoma whose initial clinical manifestation was a metastasis to a thyroid neoplasm and only the third reported example of a colonic adenocarcinoma metastatic to a thyroid tumor. In a review of previously reported examples of tumor-to-tumor metastases involving a thyroid neoplasm as the recipient, the following features were present in the majority: (i) multifocality of the metastatic tumor aggregates; (ii) a total lack of, or only minimal amounts of reaction (desmoplastic, inflammatory or myxoid) of the recipient tumor to the metastatic deposits; and (iii) retention of the histopathologic characteristics of the donor tumor in the metastatic deposits. In general, strikingly divergent morphologic features in an otherwise typical thyroid neoplasm should elicit a differential diagnosis that takes into consideration the possibility of metastasis.