Luca Barresi

Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home.

PURPOSE The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. PATIENTS AND METHODS A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. RESULTS differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. CONCLUSION Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.

Endoscopic ultrasound-guided transmural drainage of infected pancreatic fluid collections with placement of covered self-expanding metal stents: a case series.

Endoscopic ultrasound-guided transmural drainage (EUS-GTD) has become the standard procedure for treating symptomatic pancreatic fluid collections. The aim of this series was to evaluate the efficacy and safety of covered self-expanding metal stent (CSEMS) placement for treating infected pancreatic fluid collections. From January 2007 to May 2010, 22 patients (18 M/4F; mean age 56.9) with infected pancreatic fluid collections (mean size, 13.2 cm) at two Italian centers were evaluated for EUS-GTD. In 20 of the 22 patients, EUS-GTD with CSEMS placement was indicated. Early complications occurred in two patients: one patient developed a superinfection, which was managed conservatively, and one experienced stent migration and superinfection, and was managed surgically. The CSEMSs were removed without difficulty in 18 patients after a median of 26 days, while stent removal failed in one patient due to inflammatory tissue ingrowth; instead it was removed during surgery performed for renal cancer. Clinical success was achieved without additional intervention in 17 patients during a mean follow-up of 610 days; only one symptomatic recurrence was observed. In our experience, EUS-GTD with CSEMS placement appears safe for the treatment of infected pancreatic fluid collections.

Investigation of an opioid response categorization in advanced cancer patients.

The aim of this study was to investigate a possible distinction in three categories of opioid response and to identify possible factors associated with a poor response. A prospective survey was carried out in 105 consecutive patients requiring morphine for at least 4 weeks before death. Mean pain intensity, opioid doses and symptom intensity at weekly intervals, pain syndromes, and the presence of psychological distress were assessed. Opioid escalation index (OEI%) was calculated from the parameters recorded. Three categories were considered, including (1) patients with slow increments of opioid dose and a mean analgesic 10-cm visual analogue scale (VAS) less than 4 (responders), (2) patients with an OEI% more than 5 but a mean VAS less than 4 (partial responders), and (3) patients with a mean VAS more than 4 (poor responders). Treating physicians were asked to make a judgment on the pain treatment difficulties on a numerical scale (0-10). Significant differences in opioid starting dose (OSD), opioid dose at--4 weeks, nausea and vomiting at--1 week, opioid maximum doses, mean VAS, and OEI were found in the three categories of response. Significant correlations with the physician judgment were found for opioid maximum dose, mean VAS, VAS at the different time intervals, the doses used at the different intervals, OEI, and confusion. Neuropathic pain was significantly associated with a judgment of poor pain outcome. The correlation between the physician judgment and the categories of opioid response was highly significant. Seven of the 12 patients in the third category (poor response) were considered as having a relevant psychological distress. The categorization of the opioid response used in this study could be used in clinical research and as an audit tool, and could be tested in other settings to compare different treatments.

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

Fully covered metallic stents in biliary stenosis after orthotopic liver transplantation

BACKGROUND AND STUDY AIMS Data from a preliminary study suggested that the placement of a fully covered metal stent may be a valid alternative to surgery in patients who do not respond to standard endoscopic treatment. The aims of the current study were to evaluate the clinical success of self-expandable metallic stents (SEMS) in a large cohort of patients and with a long followup,and the effectiveness of SEMS placement as a first-line procedure. MATERIALS AND METHODS Between January 2008 and August 2010, 54 consecutive patients with biliary complications following orthotopic liver transplantation were treated with SEMS placement:39 after failure of conventional endoscopic therapy (Group I), and 15 with no previous endoscopic treatment who were undergoing SEMS placement as first-line treatment for complications(Group II). RESULTS In Group I, resolution after SEMS removal was observed in 71.8% of patients. Mean followup after resolution was 22.1 ±10 months. Recurrence of the complication was observed in 14.3%of patients after a mean of 8.5 months and SEMS migration was observed in 33.3% of patients. In Group II, resolution was observed in 53.3% of patients.Mean follow-up after resolution was 14.4±2.2 months. Recurrence was observed in 25% of patients and SEMS migration was observed in 46.7 %. CONCLUSIONS For endotherapy of biliary complications after orthotopic liver transplantation, metallic stents should not be used as the primary modality. In patients in whom the standard approach fails, treatment with temporary SEMS placement can solve biliary complications in almost three-quarters of cases; however stent migration(33 %) remains a problem.

Methadone Response in Advanced Cancer Patients with Pain Followed at Home

Concerns about the safety of therapy with methadone, which may arise because of its pharmacokinetic characteristics and inappropriate dosing, may deter clinicians from using this drug, especially in elderly patients. Experience is accumulating that the drug may be used safely and successfully if low doses are given initially and care is taken in the titration of the dose against the pain. A prospective study was carried out in a consecutive sample of 45 advanced cancer patients followed at home, who had never received other strong opioids for their pain. Patients were treated with an oral liquid preparation of methadone, which was administered 2-3 times daily, according to need. Doses were kept as low as possible and were titrated to achieve acceptable analgesia with minimal adverse effects. The methadone starting dose (MSD) at referral, the maximum dose of methadone (MMD), the days of methadone treatment, the use of other nonopioid analgesics, symptoms associated with methadone therapy, pain intensity, and pain mechanism were recorded. Methadone escalation index percentage (MEI%) and methadone escalation index in mg (MEI mg) were calculated from these parameters. No correlations between age and gender, and MSD, MMD, days on methadone, VAS and symptoms were found. No significant differences were found in pain mechanisms, age, and other parameters, including methadone-related symptoms. Treatment of pain with methadone provides important support to patients with cancer followed at home and the risks are low with individually titrated doses, even in older patients or in the presence of a neuropathic pain mechanism.

Opioid-sparing effect of diclofenac in cancer pain.

This study investigated the opioid-sparing effect of diclofenac using patient-controlled analgesia with oral methadone. Fifteen patients with advanced cancer participated. After achieving adequate analgesia with regular dosing of oral methadone (T1), patient-controlled analgesia with methadone was administered for 3 days (T2). Intramuscular diclofenac 75 mg twice daily was then added to this regimen for 3 days (T3). Compared to T2 values, methadone dose was significantly reduced at T2 and T2, and pain report (recorded on a visual analogue scale) was significantly reduced at T3. A reduction in methadone plasma concentration was also observed at T2 and T3, although it did not attain statistical significance. Significant decreases in the intensity of several symptoms other than pain were also found at T2 and T3. Diclofenac appears to have a relevant opioid-sparing effect when using patient-controlled analgesia with oral methadone.

Pancreatic cystic lesions: How endoscopic ultrasound morphology and endoscopic ultrasound fine needle aspiration help unlock the diagnostic puzzle

Cystic lesions of the pancreas are being diagnosed with increasing frequency, covering a vast spectrum from benign to malignant and invasive lesions. Numerous investigations can be done to discriminate between benign and non-evolutive lesions from those that require surgery. At the moment, there is no single test that will allow a correct diagnosis in all cases. Endoscopic ultrasound (EUS) morphology, cyst fluid analysis and cytohistology with EUS-guided fine needle aspiration can aid in this difficult diagnosis.

Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures

BACKGROUND Brushing is the most commonly used technique for biliary sampling at ERCP, despite its limited sensitivity. OBJECTIVE To evaluate intraductal aspiration (IDA) as a new combined endoscopic technique for cytodiagnosis, its cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. DESIGN Prospective, observational study. SETTING Single tertiary referral center. MAIN OUTCOME MEASUREMENTS IDA cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. PATIENTS AND METHODS From April 2009 to September 2010, 42 consecutive patients with suspected malignant biliary stricture underwent ERCP, with tissue sampling obtained with IDA. IDA included performance of standard brushing in all patients. After standard brushing, to perform IDA, we removed the brush from its catheter and used the tip of the catheter as a scraping device. The tip was scraped back and forth across the stricture at least 10 times. The catheter and a suction line were connected to a specimen trap to obtain intraductal aspiration of fluids and samplings. RESULTS Our cytopathologists found adequate cellular yield in 39 of the 42 IDA samples (92.8%) versus 15 of the 42 brushing samples (35.7%) (P < .001). IDA showed a significantly higher sensitivity than brushing (89% vs 78% for adequate samples and 89% vs 37% for all samples) and provided significantly superior cellular adequacy (92.8% vs 35.7%). LIMITATIONS Observational study, small number of patients. CONCLUSIONS IDA significantly improves brushing cellular adequacy and has high sensitivity for cancer detection. It was also safe, simple, rapid, and applicable during routine diagnostic ERCP, with no additional costs.

Endoscopic ultrasound-guided fine needle aspiration and biopsy using a 22-gauge needle with side fenestration in pancreatic cystic lesions

BACKGROUND Cytologic diagnosis by endoscopic ultrasound-guided fine needle aspiration is associated with low sensitivity and adequacy. A newly designed endoscopic ultrasound-guided fine needle biopsy device, endowed with a side fenestration, is now available. AIMS We carried out a study with the aim of evaluating the feasibility, safety, and diagnostic yield of the 22-gauge needle with side fenestration for endoscopic ultrasound fine needle aspiration and biopsy of pancreatic cystic lesions. METHODS 58 patients with 60 pancreatic cystic lesions consecutively referred for endoscopic ultrasound guided-fine needle aspiration were enrolled in a prospective, dual centre study, and underwent fine needle aspiration and biopsy with the 22-gauge needle with side fenestration. RESULTS Fine needle aspiration and biopsy was technically feasible in all cases. In 39/60 (65%) pancreatic cystic lesions, the specimens were adequate for cyto-histologic assessment. In lesions with solid components, and in malignant lesions, adequacy was 94.4% (p = 0.0149) and 100% (p = 0.0069), respectively. Samples were adequate for histologic evaluation in 18/39 (46.1%) cases. There were only 2 (3.3%) mild complications. CONCLUSIONS Fine needle aspiration and biopsy with the 22-gauge needle with side fenestration is feasible, and superior to conventional endoscopic ultrasound-guided fine needle aspiration cytology from cystic fluid, particularly in pancreatic cystic lesions with solid component or malignancy, with a higher diagnostic yield and with no increase in complication rate.