Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h2 = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h2 = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.

Assessment of automated cone-beam CT vessel identification software during transarterial hepatic embolisation: radiation dose, contrast medium volume, processing time, and operator perspectives compared to digital subtraction angiography.

AIM: To evaluate arterial cone-beam computed tomography (A-CBCT) automated analysis software for identification of vessels supplying tumours during transarterial hepatic embolisation (TAE). MATERIALS AND METHODS: This study was approved by the institutional review board, with waiver of consent. Consecutive TAE procedures using arterial mapping software (AMS), and performed between February 2014 and August 2014, were reviewed. Hepatic arteries were imaged using digital subtraction angiography (DSA) as well as A-CBCT processed with AMS. Interventional radiologists reported1 potential embolisation target vessels computed using AMS versus DSA alone,2 modification of the embolisation plan based on AMS, and3 operator confidence related to technical success. Imaging set-up, processing time, radiation dose, and contrast media volume were recorded. RESULTS: Thirty of 34 consecutive procedures were evaluated retrospectively. At least one additional embolisation target vessel was identified using AMS in 13 procedures (43%, 95% confidence interval [CI]: 26-61%) and embolisation plan modified in 11 (37%, 95% CI: 19-54%). Radiologists reported AMS increased operator confidence and reduced the number of DSA acquisitions in 25 (83%, 95% CI: 70-97%) and 15 cases (50%, 95% CI: 32-68%), respectively. The average A-CBCT acquisition and processing time was 4 minutes 53 seconds and 3 minutes 45 seconds, respectively. A-CBCT contributed to 11% of the radiation dose and 18% of the contrast media volume. CONCLUSION: Physicians report increased tumour supplying vessel detection and intraprocedural confidence using AMS during TAE without substantial impact on radiation dose, contrast media volume, and procedure time.

Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction.

BACKGROUND: Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. MATERIALS AND METHODS: Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy-Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed preprocedure and at 1 and 4 weeks following PBD. RESULTS: A total of 109 (60 male/49 female) patients enrolled; 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were 2 procedure-related deaths. All-cause mortality was 10% (N = 11) at 4 weeks and 28% (N = 31) at 8 weeks post-PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P < .01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P < .01). CONCLUSIONS: PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population.

Radiofrequency ablation in the management of liver metastases from breast cancer.

OBJECTIVE: Systemic chemotherapy remains the standard treatment for patients with breast cancer hepatic metastases. Resection of metastases has survival advantages in a small percentage of selected patients. Radiofrequency ablation has been used in small numbers of selected patients. This small series was undertaken to review our experience with radiofrequency ablation in the management of patients with breast cancer hepatic metastases. CONCLUSION: Radiofrequency ablation of breast cancer hepatic metastases is safe and may be used to control hepatic deposits in patients with stable or no extrahepatic disease.

Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis.

INTRODUCTION: The purpose of this study was to compare rates and patterns of disease progression following percutaneous, image-guided radiofrequency ablation (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases. METHODS: We identified 30 patients who underwent nonanatomic wedge resection for solitary liver metastases and 22 patients who underwent percutaneous RFA because of prior major hepatectomy (50%), major medical comorbidities (41%), or relative unresectability (9%). Serial imaging studies were retrospectively reviewed for evidence of local tumor progression. RESULTS: Patients in the RFA group were more likely to have undergone prior liver resection, to have a disease-free interval greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA) level before treatment. Two-year local tumor progression-free survival (PFS) was 88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group underwent re-ablation, and two patients underwent resection to improve the 2-year local tumor disease-free survival to 55%. Approximately 30% of patients in each group presented with distant metastasis as a component of their first recurrence. Median overall survival from the time of resection was 80 months in the Wedge group vs 31 months in the RFA group. However, overall survival from the time of treatment of the colorectal primary was not significantly different between the two groups. CONCLUSIONS: Local tumor progression is common after percutaneous RFA. Surgical resection remains the gold standard treatment for patients who are candidates for resection. For patients who are poor candidates for resection, RFA may help to manage local disease, but close follow-up and retreatment are necessary to achieve optimal results.

Routine urine culture at the time of percutaneous urinary drainage: does every patient need one?

PURPOSE: To determine the clinical variables associated with bacteriuria in patients undergoing primary percutaneous antegrade urinary drainage procedures in order to predict the utility of routinely obtaining urine cultures at the time of the procedure. METHODS: Between October 1995 and March 1998 urine cultures were prospectively obtained in all patients undergoing a primary percutaneous antegrade urinary drainage procedure. One hundred and eighty-seven patients underwent 264 procedures. Results were available in 252 cases. Culture results were correlated with clinical, laboratory, and demographic variables. Anaerobic cultures were not uniformly performed. RESULTS: Urine cultures were positive in 24 of 252 (9.5%) cases. An indwelling or recently removed ipsilateral device (catheter or stent) and a history of previous cystectomy with urinary diversion were significant predictors of a positive culture. Patients without either of these predictors, and without clinical or laboratory evidence of infection, were rarely found to have positive cultures. CONCLUSION: The likelihood of a positive urine culture can be predicted on the basis of the aforementioned clinical variables. In the absence of these clinical indicators routine urine cultures are neither useful nor cost-effective.

Upper urinary tract metastases from adenocarcinoma of the colon.

An unusual presentation of colorectal metastasis to the upper urinary tract is reported. The metastasis manifested as a filling defect seen during antegrade pyelography. Cytologic evaluation of aspirated material demonstrated metastatic colonic adenocarcinoma. A dilated collecting system may be caused by intraluminal material including tumor and blood clots. Whenever fixed filling defects are encountered, urine cytology should be sent even in the absence of renal parenchymal involvement by tumor. The cytological evaluation may allow for prompt diagnosis and treatment.

Portal vein embolization with use of polyvinyl alcohol particles.

Preoperative portal vein embolization has been used as method of inducing compensatory hypertrophy in the future remnant liver since it was first described in the late 1980s. Many different vascular embolic agents have been successfully used for this procedure, and there is no general consensus regarding which is the best agent. Polyvinyl alcohol (PVA) particles commonly used for arterial embolization come in many sizes, are readily available, and are easy to administer via conventional catheters. We describe an easy, safe, and effective method of the use of PVA particles for portal vein embolization.

Diagnostic imaging approaches and relationship to hepatobiliary cancer staging and therapy.

Diagnostic imaging plays an essential role in management of hepatobiliary tumors. High resolution images provided by computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) allow detection of tumor within the liver. CT arterial portography remains the standard for detection of small lesions in the range of 1.5 cm, but noninvasive techniques such as contrast-enhanced helical CT and MR hold promise for comparable lesion detection. MRI provides lesion characterization for differentiation of benign and malignant tumors. Lesion characterization has been further improved by faster CT and MR techniques that allow imaging in both arterial and portal venous phases for characterization of lesions based on the rate and pattern of enhancement. Functional imaging such as 2-fluoro-2-deoxy-D-glucose-positron-emission tomography (FDG-PET) is increasingly utilized for detection of intrahepatic tumor and extrahepatic disease. Accuracy of FDG-PET for extrahepatic disease is better than conventional imaging and has been shown to change management in a significant number of patients. Imaging is also invaluable for surgical planning. Segmental anatomy is well shown by CT, MRI, and US. CT or MR angiography with newer 3D techniques delineate vascular variants and areas of encasement or occlusion by tumor. Biliary involvement at the hilus may be shown by US and MR cholangiography. Imaging detection of vascular involvement, bile duct extension, and lobar atrophy may alter the surgical approach.

Recognition of intrabiliary hepatic metastases from colorectal adenocarcinoma.

Intrinsic involvement of bile ducts, by metastatic colorectal adenocarcinoma growing from within or invading the lumen of bile ducts, is not a well recognized pattern of tumor growth. Clinical, radiographic, operative, and histopathologic aspects of 15 patients with intrabiliary colorectal metastases were described. Fourteen patients were explored for possible hepatic resection. Two had jaundice, two radiographic evidence of an intrabiliary filling defect, 10 intraoperative evidence of intrabiliary tumor, and six microscopic evidence of intrabiliary tumor. Eleven patients underwent hepatic resection. Five of the resected patients developed hepatic recurrence. Four patients were explored for possible repeat resection. One had jaundice, one radiographic evidence of an intrabiliary filling defect, all had intraoperative evidence of intrabiliary tumor, and three microscopic evidence of intrabiliary tumor. Three patients underwent repeat hepatic resection. All patients with preoperative jaundice and radiographic evidence of an intrabiliary filling defect were unresectable. Overall, actuarial five-year survival is 33% for those patients resected versus 0% for those not resected. Intraoperative recognition of intrabiliary tumor at exploration for hepatic resection was more common than clinical, radiographic, or histopathologic recognition. More diligent examination of resected liver tissue by the surgeon and pathologist may increase identification of bile duct involvement and aid in achieving adequate tumor clearance.

Hepatic neuroendocrine metastases: does intervention alter outcomes?

BACKGROUND: In most instances, advanced neuroendocrine tumors follow an indolent course. Hepatic metastases are common, and although they can cause significant pain, incapacitating endocrinopathy, and even death, they are usually asymptomatic. The appropriate timing and efficacy of interventions, such as hepatic artery embolization (HAE) and operation, remain controversial. STUDY DESIGN: The records of 85 selected patients referred for treatment of hepatic neuroendocrine tumor metastases between 1992 and 1998 were reviewed from a prospective database. A multidisciplinary group of surgeons, radiologists, and oncologists managed all patients. Overall survival among this cohort is reported and prognostic variables, which may be predictive of survival, are analyzed. RESULTS: There were 37 men and 48 women, with a median age of 52 years. There were 41 carcinoid tumors, 26 nonfunctional islet cell tumors, and 18 functional islet cell tumors. Thirty-eight patients had extrahepatic metastases, and in 84% of patients, the liver metastases were bilobar. Eighteen patients were treated with medical therapy or best supportive care, 33 patients underwent HAE, and 34 patients underwent hepatic resection. Both the HAE-related mortality and the 30-day operative mortality rates were 6%. By univariate analysis, earlier resection of the primary tumor, curative intent of treatment, and initial surgical treatment were associated with prolonged survival (p < 0.05). On multivariate analysis, only curative intent to treat remained significant (p < 0.04). Patients with bilobar or more than 75% liver involvement by tumor were least likely to benefit from surgical resection. One-, 3-, and 5-year survival rates for the entire group were 83%, 61%, and 53%, respectively. The 1-, 3-, and 5-year survivals for patients treated with medical therapy, HAE, and operation were 76%, 39%, and not available; 94%, 83%, and 50%; and 94%, 83%, and 76%, respectively. CONCLUSIONS: Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellent palliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative.

Up-regulation of retinoic acid receptor beta expression in renal cancers in vivo correlates with response to 13-cis-retinoic acid and interferon-alpha-2a.

Retinoic acid receptor-beta (RAR-beta) mRNA is not expressed by retinoid-resistant renal cancer cell lines but is present in retinoid-sensitive SK-RC-06 renal cancer cells and increases following incubation with retinoic acid (RA), suggesting that the antitumor action of RA is mediated through RAR-beta (A. D. Hoffman et al., Clin. Cancer Res., 2: 1077-1082, 2996). To determine whether RAR-beta expression correlates in vivo with major clinical response to patients with renal cell carcinoma (RCC) who were treated with retinoid-based therapy, we used in situ hybridization to analyze RAR-beta expression in tumor specimens obtained from patients who were treated on a clinical trial with 13-cis-RA and IFN-alpha. Thirty-three tissue specimens were analyzed (23 pretreatment and 10 on-treatment). mRNA expression was based on staining intensity, with scores within tumor cells ranging from 0 to 2, where a score of 0 indicated absence of staining, a score of 1 indicated weak staining, and a score of 2 indicated strong staining. RAR-beta expression was present in 22 of 23 (96%) pretreatment and 9 of 10 (90%) on-treatment specimens. Pretreatment levels of expression did not associate with the site of biopsy and did not predict for major clinical response to RA plus IFN-alpha therapy (two-sided Fisher's exact test, P = 0.826). However, an increase in the intensity of RAR-beta mRNA expression was detected in four of five (80%) patients who achieved a major response but in none of the five patients with progressive disease in whom sequential biopsies were available (two-sided Fisher's exact test, P = 0.048). These data show that RAR-beta transcripts increase in tumor cells of RCC patients who clinically respond to retinoid-based therapy. Retinoids that potently induce RAR-beta expression should be evaluated in the treatment of advanced RCC.

Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms.

PURPOSE: To evaluate treatment outcome with respect to the indication for treatment in patients with neuroendocrine tumors metastatic to the liver undergoing hepatic artery embolization with polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS: Charts and radiographs were reviewed of 35 patients undergoing 63 separate sessions of embolotherapy between January 1993 and July 1997. Patient demographics, tumor type, indication for embolization, and complications were recorded. Symptomatic and morphologic responses to therapy were noted, as well as duration of response. RESULTS: Fourteen men and 21 women underwent embolization of 21 carcinoid and 14 islet cell tumors metastatic to the liver. These patients underwent 63 separate episodes of embolotherapy. Of 48 episodes that could be evaluated, response to treatment was noted following 46 episodes (96%). The duration of response was longest in patients treated for hormonal symptoms with (17.5 months) or without (16 months) pain, and was shortest (6.2 months) when the indication was pain alone. Complications occurred after 11 of the 63 embolizations (17%), including four (6%) deaths. Cumulative 5-year survival following embolotherapy was 54%. CONCLUSION: Hepatic artery embolization with PVA particles is beneficial for patients with neuroendocrine tumors metastatic to the liver and may be used for control of pain as well as hormonal symptoms. This therapy should be used cautiously when more than 75% of the hepatic parenchyma is replaced by tumor.

Particle embolization for hepatocellular carcinoma.

PURPOSE: To evaluate the outcome of all patients undergoing particle embolization for hepatocellular carcinoma at a single institution from January 1, 1993, through December 31, 1995. MATERIALS AND METHODS: The charts and radiographs of all patients undergoing particle embolization during the study period were reviewed. The following information was collected: patient demographics, Child class and Okuda stage, number of embolization treatment sessions, length of hospital stay, complications related to the embolization procedure, including postembolization syndrome, current patient status, and date of death. RESULTS: Forty-six patients underwent 86 embolization sessions during the study period. Postembolization syndrome developed after 70 of the 86 sessions (81%); in four cases (4.6%) this required treatment that extended the patient's hospital stay. Three other complications occurred (3.5%), including a splenic infarct and two episodes of transient hepatic failure, all treated supportively. There was one death within 30 days, but it was not directly attributable to embolotherapy. Follow-up was available for all of the patients who underwent treatment. Thirty-four patients were classified as Child class A, and 12 were classified as Child class B. Thirty patients were classified as Okuda stage I, 14 were classified as Okuda stage II, and two were classified as Okuda stage III. Overall actuarial survival was 50% at 1 year and 33% at 2 years. There was a statistically significant difference in survival between Okuda stage I and stage II patients, but not between Child class A and class B patients. CONCLUSION: Particle embolization for hepatocellular carcinoma is well tolerated and demonstrates actuarial survival of 50% at 1 year and 33% at 2 years.

Clinical factors associated with positive bile cultures during primary percutaneous biliary drainage.

PURPOSE: To evaluate the utility of routine bile cultures and to determine the risk factors for bacterial colonization of the bile as well as the biliary flora in patients with biliary obstruction undergoing primary percutaneous biliary drainage. MATERIALS AND METHODS: Between October 1995 and January 1997, bile cultures were prospectively obtained in all patients undergoing percutaneous biliary drainage. Seventy-six patients underwent 86 procedures. Culture results were correlated with clinical, laboratory, and demographic variables. The antibiotic sensitivities of cultured organisms were examined. RESULTS: Fever, previous endoscopic or percutaneous biliary instrumentation, and bilioenteric anastomosis were significant predictors of a positive bile culture. In the absence of any of these indicators, bile cultures were unlikely to be positive. Enterococcus species was the organism isolated most commonly. Yeast, gram-negative aerobic bacilli, and Streptococcus viridans followed in frequency. CONCLUSION: Bile cultures provide valuable information that was useful for planning antibiotic prophylaxis and treatment. The likelihood of positive bile cultures can be predicted based on certain clinical variables. Continued investigation is needed to better predict bacterial flora in individual patients. Given the association between previous instrumentation and biliary colonization, noninvasive imaging modalities should be exhausted before invasive procedures are performed for solely diagnostic purposes in patients with biliary obstruction.

MRI as an alternative to CT-guided biopsy of adrenal masses in patients with lung cancer.

BACKGROUND: This study was performed to assess chemical shift magnetic resonance imaging (CSMRI) for characterizing adrenal masses in patients with lung cancer, and to compare charges associated with two algorithms for assessing adrenal masses in these patients. METHODS: Forty-two patients with lung cancer underwent both CSMRI (using in-phase and opposed-phase gradient echo images) and computed tomography-guided percutaneous biopsy of adrenal masses. Adrenal-to-spleen signal intensity ratios on the opposed-phase images were correlated with histopathologic results. The normalized charges for two algorithms were compared. In algorithm A, computed tomography-guided biopsy is used first to evaluate an adrenal mass; in algorithm B, CSMRI is used first, followed by computed tomography-guided biopsy only if CSMRI findings are not diagnostic of adenoma. RESULTS: Biopsy showed 24 (57%) adrenal adenomas and 18 (43%) metastases. Chemical shift magnetic resonance imaging was 96% sensitive for adenoma and 100% specific. The average normalized charges associated with algorithm A were $1,905 per patient versus $1,890 with algorithm B. CONCLUSIONS: Initial use of CSMRI in evaluating an adrenal mass in lung cancer patients can obviate biopsy in 55% of patients, and its charges are similar to those for performing computed tomography-guided biopsy in all patients.

Outpatient treatment of iatrogenic pneumothorax after needle biopsy.

PURPOSE: To evaluate prospectively the feasibility of treating iatrogenic pneumothorax after fine-needle aspiration biopsy (FNAB) of the lung with short-term placement of a small-caliber chest tube and to determine whether a 1-hour clamping trial is adequate to identify patients with persistent air leak. MATERIALS AND METHODS: All patients undergoing FNAB of lung masses over a 28-month period were entered into the study. Patients with symptomatic, enlarging, or greater than 30% pneumothorax were treated with an 8-F chest tube. After 2 hours, the chest tube was clamped, and if the lung remained expanded for an additional hour, the chest tube was removed and the patients were discharged after a brief observation period. Patients were followed up by telephone after 24 hours. RESULTS: Three hundred fifteen patients underwent FNAB of the lung. Sixty-eight patients (22%) developed a pneumothorax. Chest tubes were placed in 14 patients (4%): Six patients (2%) required admission to the hospital (four for air leaks), and the other eight patients were treated successfully as outpatients, with removal of the chest tube before discharge the day of FNAB. CONCLUSION: Patients who develop clinically important pneumothorax after FNAB can be safely treated with short-term, small-caliber chest tubes and require hospital admission only if they demonstrate evidence of continued air leak.

Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies.

OBJECTIVE: This study was performed to compare two proposed algorithms used when evaluating an adrenal mass discovered during staging evaluation of a patient with a known malignancy. Such evaluation was meant to lead to determination of the relative charges associated with each algorithm. SUBJECTS AND METHODS: Fifty-four patients with known malignancies who required evaluation of an adrenal mass underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital charges incurred for each procedure and any associated complications were normalized using national relative-value scale charges and conversion factors. A decision analysis was performed to compare the relative charges that would have been incurred if adrenal MR imaging had been performed in all patients, followed by CT-guided biopsy only in those patients with MR findings not diagnostic of adrenocortical adenoma, and the relative charges incurred if only CT-guided adrenal biopsy had been performed in every patient. RESULTS: Twenty-three (43%) of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma were 94% and 100%, respectively. The charges incurred by performing MR imaging as the initial examination with subsequent CT-guided biopsy only in those patients with CSI findings not diagnostic of adenoma would have been similar to those incurred by first performing CT-guided adrenal biopsy in every patient. CONCLUSION: CSI is an accurate, noninvasive technique for evaluating adrenal masses in patients with cancer. If CT-guided biopsy is used only when CSI is not diagnostic of adrenocortical adenoma, the associated charges would be virtually the same as when CT-guided biopsy is performed as the first test in every patient. Moreover, biopsies could have been avoided in 54% of these patients.