Application of 18 F-fluorodeoxyglucose PET/CT radiomic features and machine learning to predict early recurrence of non-small cell lung cancer after curative-intent therapy.

OBJECTIVE: To predict the recurrence of non-small cell lung cancer (NSCLC) within 2 years after curative-intent treatment using a machine-learning approach with PET/CT-based radiomics. PATIENTS AND METHODS: A total of 77 NSCLC patients who underwent pretreatment 18 F-fluorodeoxyglucose PET/CT were retrospectively analyzed. Five clinical features (age, sex, tumor stage, tumor histology, and smoking status) and 48 radiomic features extracted from primary tumors on PET were used for binary classifications. These were ranked, and a subset of useful features was selected based on Gini coefficient scores in terms of associations with relapsed status. Areas under the receiver operating characteristics curves (AUC) were yielded by six machine-learning algorithms (support vector machine, random forest, neural network, naive Bayes, logistic regression, and gradient boosting). Model performances were compared and validated via random sampling. RESULTS: A PET/CT-based radiomic model was developed and validated for predicting the recurrence of NSCLC during the first 2 years after curation. The most important features were SD and variance of standardized uptake value, followed by low-intensity short-zone emphasis and high-intensity zone emphasis. The naive Bayes model with the 15 best-ranked features displayed the best performance (AUC: 0.816). Prediction models using the five best PET-derived features outperformed those using five clinical variables. CONCLUSION: The machine learning model using PET-derived radiomic features showed good performance for predicting the recurrence of NSCLC during the first 2 years after a curative intent therapy. PET/CT-based radiomic features may help clinicians improve the risk stratification of relapsed NSCLC.

Clinical Experiences of High-Risk Pulmonary Thromboembolism Receiving Extracorporeal Membrane Oxygenation in Single Institution.

BACKGROUND: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO. METHODS: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed. RESULTS: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7). CONCLUSION: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Necrotizing sarcoid granulomatosis simulating pulmonary malignancy: A case report.

RATIONALE: Necrotizing sarcoid granulomatosis (NSG) has recently been termed "sarcoidosis with NSG pattern" for the disease entity representing nodular sarcoidosis with granulomatous pulmonary angiitis. It is characterized by sarcoid-like granulomas, vasculitis, and a variable degree of necrosis. Its rarity and nonspecific clinical symptoms can easily lead to misdiagnosis or delayed diagnosis. PATIENT CONCERNS: We report a 67-year-old female with a biopsy-confirmed sarcoidosis with NSG pattern mimicking pulmonary malignancy on initial chest computed tomography scan. DIAGNOSES: Sarcoidosis with NSG pattern. INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery with a lung biopsy. No further treatment was performed after the lung biopsy. OUTCOMES: Follow-up imaging studies revealed spontaneous regression of the disease after 2 months. LESSONS: Awareness of this rare benign disease entity and overlapping radiologic manifestations with pulmonary malignancy or other granulomatous diseases can be helpful for making a precise diagnosis with a better differential diagnosis.

Therapy-related myeloid leukemia during erlotinib treatment in a non-small cell lung cancer patient: A case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are tolerable drugs used for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Serious adverse reactions are uncommon compared with cytotoxic drugs. CASE SUMMARY: A 52-year-old man presented with general weakness and cytopenia. He had been taking erlotinib for 11 mo to treat NSCLC. The pathological diagnosis from the right upper lobe mass was adenocarcinoma with an EGFR mutation in exon 21 (L858R). He had previously received paclitaxel/carboplatin, gemcitabin/ vinorelbine chemotherapy, stereotactic radiosurgery for brain metastasis, and whole-brain radiotherapy as treatment for NSCLC. We diagnosed the patient with acute myeloid leukemia (AML). During the induction and consolidation chemotherapy for AML, the erlotinib was discontinued. When complete remission of the AML was achieved, since the lung masses were increased, pemetrexed/ cisplatin for the NSCLC was initiated. After two cycles of chemotherapy, the cytopenia was prolonged. AML relapse occurred with the same karyotype. CONCLUSION: Therapy-related acute myeloid neoplasm (t-MN) is a rare but fatal late complication. Although a patient may be taking EGFR-TKIs, the possibility of t-MN should be considered. Further studies are needed to determine whether EGFR-TKI usage is a predisposing factor for t-MN.

Missed Lung Cancers on Chest Radiograph: An Illustrative Review of Common Blind Spots on Chest Radiograph with Emphasis on Various Radiologic Presentations of Lung Cancers.

Missed lung cancers on chest radiograph (CXR) may delay the diagnosis and affect the prognosis. CXR is the primary imaging modality to evaluate the lungs and mediastinum in daily practice. The purpose of this article is to review chest radiographs for common blind spots and highlight the importance of various radiologic presentations in primary lung cancer to avoid significant diagnostic errors on CXR.

The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line.

BACKGROUND/AIMS: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. METHODS: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1ß (IL-1ß), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. RESULTS: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1ß in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1ß in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1ß by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1ß secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. CONCLUSIONS: The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Increased antioxidant activity after exposure of ozone in murine asthma model.

BACKGROUND: Ozone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma. OBJECTIVE: This study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity. METHODS: Three parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day. RESULTS: Airway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model. CONCLUSION: Murine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review.

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor.

p53 Expression in a Malignant Mesothelioma Patient during Seven-Year Follow-up.

Malignant mesothelioma (MM) is the aggressive tumor of serosal surfaces. There are crude pathogenetic results regarding the biology of MM. Coordinated upregulations of p53 gene expression are shown in malignancies. We believed that there are changes in the p53 expression with transformation from reactive hyperplasia to MM. A 65-year-old male was admitted the hospital because of left pleuritic chest pains in 2004. Chest computed tomography (CT) results showed left pleural effusions with loculation and pleural thickening. Pathologic findings revealed reactive mesothelial hyperplasia. In 2008, the patient again felt left pleuritic chest pains. Chest CT showed progressive thickening of the left pleura. Pathologic diagnosis was atypical mesothelial hyperplasia. In 2011, chest CT showed progressive thickening of his left pleura. He was diagnosed with well-differentiated papillary mesothelioma. Serial change was analyzed by immunohistochemical staining for p53 of pleural tissues. There were no remarkable changes in p53 expressions during the transformation to MM.

Genome-wide association study identifies ALLC polymorphisms correlated with FEV1 change by corticosteroid.

OBJECTIVES: Asthma can be suppressed by inhaled corticosteroids (ICS). However, response to ICS shows marked inter-individual variability. This study is aimed to identify the genetic variants associated with the change in the percentage of forced expiratory volume in 1second (%ΔFEV1) following ICS treatment. METHODS: A genome-wide association study was performed in a Korean asthmatic cohort. To further investigate these genetic associations, 11 additional single-nucleotide polymorphisms (SNPs) on the allantoicase (ALLC) gene were selected from the HapMap database and genotyped in the same asthmatic patients in the follow-up study. RESULTS: In a genome-wide study, we identified the lowest P-value in ALLC, but none of the SNPs met the genome-wide association criteria (P<1.0×10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %ΔFEV1 in the study subjects (P<3.73×10(-6)). CONCLUSIONS: Although the associated signals could not overcome the genome-wide multiple correction due to small sample size (n=189), our results suggest that associated SNPs of ALLC might be genetic predictors of response to ICS, at least with respect to ΔFEV1 in Korean asthmatics.

Effect of rivaroxaban on fibrinolytic therapy in massive pulmonary embolism: two cases.

The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis in massive PE is regarded as a life-saving intervention, unless there is a high risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an oral factor Xa inhibitor, however its anticoagulation effects before or after administration of fibrinolytics in massive PE are still unknown. Two patents were admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was admitted with dyspnea and poor oral intake. Systemic arterial hypotension with radiologic confirmation led to a diagnosis of massive PE in both patients. Rivaroxaban was administered before in one, and after firbrinolytic therapy in the other. One showed similar efficacy of rivaroxaban with currently used anticoagulants after successful fibrinolysis, and the other one without antecedent administration of the fibrinolytic agent showed unfavorable efficacy of rivaroxaban.

Association of serum leptin and adiponectin with obesity in asthmatics.

BACKGROUND: Mounting evidence implicates obesity as a major risk factor for asthma. Leptin and adiponectin produced by fat tissues play a critical role in the regulation of body weight and allergic inflammation. OBJECTIVE: The aim of this study was to evaluate the effects of leptin and adiponectin on development of asthma. METHODS: We measured the leptin and adiponectin in serum from patients with asthma (n = 60) and normal control subjects (n = 30) by enzyme-linked immunosorbent assay. RESULTS: Logarithmic leptin and adiponectin concentration was not different between asthmatics and control subjects. Although the logarithmic adiponectin level was not different by gender in asthmatics, the logarithmic leptin concentration was significantly higher in females than in male asthmatics (2.41 +/- 0.05 ng/mL vs. 2.01 +/- 0.05 ng/mL, p = 0.001). The leptin/adiponectin ratio was also significantly higher in females than in male asthmatics. The leptin/adiponectin ratio was correlated with body mass index (r = 0.210, p = 0.05) in asthmatics. CONCLUSION: Our results suggest that serum leptin and adiponectin may be associated with gender and obesity regardless of development of asthma.

Association of IL-17RB gene polymorphism with asthma.

BACKGROUND: Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL-17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-kappaB. OBJECTIVES: We examined the association of polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the effects of those polymorphisms on the transcription of various IL-17RB isoforms. METHODS: In total, 954 asthmatic patients or 265 healthy control subjects were screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA expression IL-17RB in B-cell lines derived from patients was also measured by reverse transcription-polymerase chain reaction. RESULTS: Direct sequencing of 24 unrelated Korean DNA samples revealed 18 genetic variants, including four insertion/deletions and 14 single-nucleotide polymorphisms (SNPs). Six of the SNPs (-1465G>A, +5661G>A, +6297T>C [Y123Y], +13797C>T, +18661C>T, and +18965G>A) were used to screen a larger group of subjects. Intronic polymorphism +5661G>A was significantly associated with the development of asthma (p = 0.001); moreover, a minor allele of IL-17RB +5661G>A appeared at a lower frequency in the asthmatic patients than in the healthy control subjects (0.13 vs 0.19, respectively). The IL-17RB messenger RNA expression in B cells homozygous for IL-17RB+ 5661GG was significantly higher than that in B cells homozygous for IL-17RB+5661AA (p = 0.002). CONCLUSIONS: A rare allele of IL-17RB +5661G>A may have a protective role against the development of asthma via regulation at the level of transcription. The SNPs identified in this study may be used to develop markers to assess the risk of asthma.

Cigarette smoking-induced acute eosinophilic pneumonia: a case report including a provocation test.

The mechanism and cause of acute eosinophilic pneumonia are largely unknown. Many factors including the smoking of cigarettes have been suggested, but none have been proven to directly cause acute eosinophilic pneumonia. The authors report a case of acute eosinophilic pneumonia in a young Asian male who recently started smoking. The diagnosis was made based on his clinical course and results of chest radiography, lung spirometry, bronchoalveolar lavage, and transbronchial lung biopsies. After administration of methylprednisolone, his clinical course rapidly improved. A provocation test was designed to establish a connection between cigarette smoking and the development of acute eosinophilic pneumonia. After the provocation test, the patient showed identical symptoms, increase in sputum eosinophils, and worsening of pulmonary function. The results of the provocation test suggest that smoking may directly cause acute eosinophilic pneumonia, and support previous reports of cigarette smoking-induced acute eosinophilic pneumonia.

Malignant mesothelioma cells are rapidly sensitized to TRAIL-induced apoptosis by low-dose anisomycin via Bim.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) holds promise for the treatment of tumors; however, many tumors are resistant to TRAIL alone. We previously showed that resistant malignant mesothelioma cells are sensitized to TRAIL-induced apoptosis by diverse toxic insults including chemotherapy, irradiation, or protein translation inhibitors such as cycloheximide. In seeking nontoxic sensitizers for TRAIL, we tested the protein translation inhibitor anisomycin at subtoxic concentrations 10- to 100-fold below those reported to inhibit protein translation. At these low concentrations (25 ng/mL), anisomycin potently and rapidly sensitized mesothelioma cells to TRAIL-induced apoptosis. Moreover, such sensitization occurred in malignant but not in nonmalignant mesothelial cells. Sensitization by anisomycin was dependent on Bid, indicating a role for mitochondrial amplification in the apoptotic synergy with TRAIL signaling. Consistent with this, we found that anisomycin induces rapid accumulation of the BH3-only protein Bim; moreover, small interfering RNA knockdown of Bim inhibits anisomycin-induced sensitization. Bim accumulation seems not to be transcriptional; instead, it is associated with Bim phosphorylation and increased stability, both consistent with the activation of c-jun NH2-terminal kinase signals by anisomycin. Overall, our data indicate that the rapid and selective sensitization by anisomycin in mesothelioma cells is mediated by posttranslational potentiation of Bim, which primes the cells for apoptosis via the death receptor pathway. Such subtoxic approaches to sensitization may enhance the value of TRAIL in cancer therapy.

Clostridium difficile small-bowel enteritis after total proctocolectomy: a rare but fatal, easily missed diagnosis. Report of a case.

PURPOSE: Clostridium difficile enteritis is a rare infection, with less than a dozen cases reported in the literature. We present a case of a patient with total proctocolectomy and ileostomy, developing Clostridium difficile infection of small bowel. We discuss the role of Clostridium difficile toxins and review previously reported cases of Clostridium difficile enteritis after total colectomy. METHODS: A 65-year-old male with a history of total proctocolectomy and ileostomy 30 years previously had purulent ileostomy drainage and septic shock. The patient was recently treated with intravenous piperacillin, tazobactam, and levofloxacin for aspiration pneumonia in the previous admission. Ileostomy stool cultures tested positive for Clostridium difficile toxin A, and the patient was promptly treated with intravenous metronidazole. RESULTS: The patient was aggressively resuscitated and treated, recovered from the enteritis and shock, but died of pulmonary complications after a prolonged hospitalization. CONCLUSIONS: Review of previously reported cases of Clostridium difficile enteritis showed a high mortality rate. We attribute this to delayed diagnosis secondary to rarity of this illness. Some patients were diagnosed only after pseudomembranes in small-bowel segments were found at autopsy. This rare disease entity is firmly established among the differential diagnosis to clinicians treating patients with total proctocolectomy.

Aberrant right subclavian artery associated with a common origin of carotid arteries.

We present a patient with a rare anomaly of the aortic arch. Angiography revealed an aberrant right subclavian artery (aRSA) originating from the middle of the aortic arch. Angiography also demonstrated an anomalous origin of the left common carotid artery sharing a common trunk with the innominate artery and a large right vertebral artery arising from the right common carotid artery. Although this particular combination of anomalies has been reported in cadaver cases, to our knowledge this is the first premortem angiographic description of a patient in which an aRSA originates from the middle of the arch between the anomalous bovine arch trunk and the left subclavian trunk.

A novel in vitro model of human mesothelioma for studying tumor biology and apoptotic resistance.

Like many tumors, malignant mesothelioma exhibits significant chemoresistance and resistance to apoptosis in vivo that is not seen in current in vitro models. To study the mechanisms of this multicellular resistance, biologically relevant in vitro models are necessary. Therefore, we characterized and tested human mesothelioma tissue grown in vitro as tumor fragment spheroids. After 5-10 d in culture, fragments from each of 15 human mesothelioma tumors rounded into spheroids. The tumor fragment spheroids maintained multiple characteristics of the original tumors for up to 3 mo including the presence of viable mesothelioma cells, macrophages, and a collagen-rich stroma. In 14-d-old spheroids, mesothelioma cells showed the same proliferation rate and expression of a death receptor, DR5, as in the original tumor. To determine responses to treatment, we treated tumor fragment spheroids grown from three separate tumors with agents, TNF-related apoptosis-inducing ligand (TRAIL) plus cycloheximide, that induced near total apoptosis in three human mesothelioma cell lines (M28, REN, MS-1) grown as monolayers (94 +/- 6% apoptosis; mean +/- SEM). Compared with mesothelioma cells in monolayers, mesothelioma cells in the spheroids were resistant to TRAIL plus cycloheximide (32 +/- 4% apoptosis; mean +/- SEM). Apoptotic resistance of mesothelioma cells was significantly reduced by inhibiting either the PI3K/Akt pathway with LY294002 (47 +/- 6% apoptosis) or the mTOR pathway with rapamycin (50 +/- 17% apoptosis). We conclude that human mesothelioma can be maintained in vitro in a biologically relevant model that exhibits apoptotic resistance, thereby permitting study of its tumor biology and of novel approaches to therapy.

Combined preemptive and preventive analgesia in morbidly obese patients undergoing open gastric bypass: A pilot study.

PURPOSE: It is difficult to balance adequate pain control against the risk of sedation and depressed breathing in severely obese patients. This study assesses the effects of combined preemptive and preventive analgesia on narcotic use after open gastric bypass. METHODS: Twenty patients were randomized in this prospective double-blind trial comparing preoperative 30 mg intravenous ketorolac (Toradol), 0.25% subcutaneous bupivacaine (Marcaine) with epinephrine along the planned incision, and 0.25% bupivacaine in the rectus fascia before closing with identical injections with 0.9% saline. The patients' self-assessed pain on a visual analogue scale (VAS) and total narcotic use by patient-controlled analgesia (PCA) and rescue medication were recorded. RESULTS: Age, body mass index (BMI), incision length, and operative times were similar between the two groups, as was the average length of hospital stay (2.9 days). Self-reported pain was less in the treatment group 1 hour postoperatively (P = .01). Narcotic use was less in the treatment group during the first 2 hospital days (51% less on day 1 vs 44.5% less on day 2). Total narcotic use during the hospital stay was reduced by 40% (P = .02). CONCLUSIONS: Patients receiving combined preemptive and preventive analgesia used significantly less narcotic pain medication than the patients receiving placebo. The effect lasted beyond the duration of action of the local anesthetic.