Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

BACKGROUND AND STUDY AIMS: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. PATIENTS AND METHODS: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. RESULTS: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CONCLUSIONS: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

[Definitive treatment of anal canal carcinoma with radiotherapy: adverse impact of a pre-radiation resection. A retrospective study of 57 patients treated with curative intent]. / Radiothérapie à visée curative du carcinome du canal anal : impact défavorable d'une résection préalable. Etude rétrospective de 57 patients traités en intention curative.

PURPOSE: To describe retrospectively the overall survival, the cancer specific survival and the tumor control in an homogeneous series of patients with epidermoid carcinoma of the anal canal treated with definitive radiotherapy; to assess the impact of brachytherapy, chemotherapy and pre-radiotherapy resection on the risk of recurrence. PATIENTS AND METHODS: From 1997 to 2007, 57 patients (pts) presenting with an epidermoid carcinoma of the anal canal (T1: 14, T2: 33, T3-4: 10, N0: 31, N1: 19, N2: 3, N3: 4, M0: 57) were treated with definitive radiotherapy by the same radiation oncologist. The treatment included an external beam irradiation (EBRT) given to the posterior pelvis (45Gy/25 fractions) and, six weeks later, a boost delivered with interstitial brachytherapy (37/57) or external beam irradiation (20/57). Twelve pts had undergone a surgical resection of the tumour before radiotherapy. A belly board was used for EBRT in 13 pts. A concurrent platinum based chemotherapy was done in 42 pts. The mean follow-up was 57 months. RESULTS: The overall survival rate at 5 years was 89% with a cause specific survival of 96%. Five patients recurred (5-year rate: 12%: four had local relapse (5-year rate: 8%), four had groin recurrence, and distant metastases were seen in two. In univariate analysis, the risk of relapse was higher in patients who had undergone a pre-radiation excision (p=0.018), in those who did not receive chemotherapy (p=0.076) and in those who were irradiated on a belly board (p=0.049). In multivariate analysis, a pre-radiotherapy resection (p=0.084) had an inverse impact on the tumour control reaching the level of statistical significance and the use of a belly board was of marginal influence (p=0.13). CONCLUSION: Radiotherapy and chemoradiation with cisplatine-based chemotherapy cure a vast majority of patients with epidermoid carcinoma of the anal canal. Therapeutic factors that may interfere with the definition of the target volume and the patients' repositioning may decrease the efficacy of radiotherapy. Pre-radiotherapy surgical resection should be avoided.

[Pitfalls of polypharmacy, particularly in the elderly]. / Complications de la polymédication, en particulier chez les personnes agées.

Many patients, especially those aged over 70 years, receive variable types of polypharmacy in western countries. Polytherapy may be naturally in accordance with good clinical practice, or vice versa, it may be unjustified, whether it results from inappropriate prescribing or self-medication. Major causes of polytherapy include the presence of multiple disease states, thereby necessitating multiple drug therapy, particularly in patients with chronic debilitating disorders; increasing demand for health care; therapeutic advances as well as excessive prescribing (which may be related to poor coordination between practitioners). Polypharmacy may result in: increased rates of adverse drug reactions, as a frequent consequence of drug-drug interactions; errors in medication-taking, including poor compliance due to drug-associated untoward effects and medication errors; both direct and indirect additional costs for the health insurance scheme. Preventive measures of adverse drug reactions should include: appropriate clinical trials to improve knowledge of risks of polytherapy in elderly patients and other patients at high risk for developing drug-related side-effects; improved adverse drug reaction reporting to the pharmaco-vigilance systems provision of information about drug side-effects to all health care professionals as well as to patients.

[Adverse drug effects: a prospective study by Apnet performed in seven emergency care units in France: propositions for preventive measures]. / Accidents médicamenteux. (A propos d'une étude prospective de l'Apnet réalisée dans sept services d'accueil et d'urgences français). Propositions pour des mesures préventives.

Various studies have shown that adverse drug effects (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence and severity of ADEs resulting in hospital visits. To address this issue, we conducted a prospective survey in primary care and emergency departments of French public hospitals. This study was performed over two periods of one week, one in January, February and one in June 2003, in primary care and emergengy departments of four university hospitals and three general hospitals throughout France. Out of a total of 1826 patients consulting, 1663 were taking at least one drug during the previous week and were included for analysis according to the protocol. Altogether, 370 (22.2%; IC 95: 20.2-24.3%) of these patients receiving at least one drug consulted because of an ADE. From these 370 patients, 263 (15.8%) where considered as touched by a probably (12), likely (13) or very likely (14) ADE. The sex ratio was the same in both groups with or without ADE (0.88%; P=0.95). Patients with ADE were older than those without (62.4 vs 53.8 years, P=0.0016). Furthermore, ADE patients were more likely to have a higher severity score than no-ADE group (P=0.0003). The outcome seemed to be worse in patients with an ADE. The percentage of patients treated with 2 or more drugs and the number of drug exposures were significantly higher in patients with ADE than in those without (93.2% vs 84.2%, P<0.0001, and 5.8 vs 4.5 P<0.0001, respectively). The most frequent causes of visits for ADE-patients were digestive (n=38: 14.4%), neurological (n=23: 10.6%), malaise (n=48: 18,2%) events. The most frequently incriminated drug classes were (1) psychotropic agents, (including anxiolytics, hypnotics, antidepressants and antipsychotics), (2) diuretics (3) anticoagulants, (4) other cardiovascular drugs and (5) analgesics, including non steroidal anti-inflammatory agents. In 150 cases (40.8%; IC 95: 33.7% - 45%), the ADE was considered to be preventable because a contra-indication or a warning about drug use had not been respected.

[Placebo effect on diastolic, systolic and pulsed arterial pressure]. / L'effet placebo sur les pressions artérielles systolique, diastolique et pulsée.

UNLABELLED: THE PLACEBO EFFECT: In controlled clinical trials, use of a placebo has demonstrated that the lowering of blood pressure in hypertensive patients under medication is associated with a reduction in cardiovascular morbidity and mortality. Although a placebo clearly lowers levels of systolic and diastolic blood pressure (to varying degrees depending on the measurement used), it does not appear to have any effect on the pulse pressure, representing the difference between the systolic and diastolic pressures. CENTRAL MECHANISMS: The absence of placebo effect on the pulse pressure, demonstrated by controlled studies, suggests the activity of central mechanisms (notably bulbar), common to the placebo effect and to the control of neurogenic coupling between the heart and the large caliber arteries. IN PRACTICE: Since the pulse pressure after the age of 60 is a major factor for predicting myocardial infarction, these results suggest that modifications in pulse pressure should be more closely studied during controlled cardiovascular clinical trials in elderly patients.

Diagnosis of a gastric mucosa-associated lymphoid tissue lymphoma by endoscopic ultrasonography-guided biopsies in a patient with a parotid gland localization.

We report the case of a 32-year-old man with a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjögren syndrome. He underwent an upper endoscopy as part of the screening of a gastric localization which showed a diffuse non-specific gastritis. However, endoscopic ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis. The search for Helicobacter pylori infection remained negative. Four months after treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal thickening of the second layer. Regression was confirmed histologically on new EUS-guided biopsies. MALT lymphoma is usually considered a localized disease; however, dissemination is probably more frequent than initially believed. Our case reflects the importance of a systematic screening for a gastric localization in patients with MALT lymphoma of the salivary glands. In this situation, association to autoimmune disease such as Sjögren syndrome is more likely to explain the gastric location than infection with H. pylori. Endoscopic ultrasonography has a major impact for the staging of gastric MALT lymphoma, but may also help diagnose focal infiltration by the disease.

Small-cell carcinoma of the esophagus: report of three cases and review of the literature with emphasis on therapy.

Primary small-cell carcinoma (SCC) of the esophagus is rare, with about 200 cases reported up till now in the literature. Like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Between 1994 and 1997, three patients with SCC of the esophagus were treated at Besançon University Hospital and this represented 1.85% of all esophageal malignancies diagnosed during this period: one patient had a limited tumor and underwent initial surgical resection, then chemotherapy with cisplatine and etoposide, and radiotherapy for recurrences. The other patients had extensive disease at diagnosis and were treated by the same chemotherapy. This retrospective study reports our experience of patients with this particular tumor and outlines the management strategy based on the available literature.

Adjuvant chemotherapy for colon carcinoma with positive lymph nodes: use and benefit in routine health care practice.

In 1990, an international consensus was reached on the efficacy of adjuvant chemotherapy for lymph node positive (stage III) colon carcinoma (CC). This study evaluates the use and benefit of such therapy in routine health care practice. The study includes all patients with stage III CC treated by putative curative surgery (n = 182) recorded at the Geneva cancer registry between 1990 and 1996. Factors modifying chemotherapy use were determined by logistic regression, considering patients with chemotherapy as cases (n = 55) and others as controls (n = 127). The effect of chemotherapy on the 5-year survival was evaluated by the Cox model. Analyses were adjusted for possible confounders. The use of chemotherapy increased over the period (P(trend) < 0.001). Age strongly modulated chemotherapy use. In 1996, 54% of eligible patients received chemotherapy, this proportion fell to 13% after age 70. Decisions to use chemotherapy significantly depended on stage, grade and cancer site. The chance to be treated was non-significantly lower among individuals of low social class, widowed and foreigners. Chemotherapy significantly decreased mortality rates (Hazard ratio: 0.35, 95%CI: 0.18-0.68), independently of the prognostic factors and with similar benefit regardless of stage and age group. Strong beneficial effect of adjuvant chemotherapy on stage III CC can be achieved in routine practice. However, this study shows that it is probably not optimally utilised in Switzerland, particularly among the elderly.

Ischemic colitis during pregnancy and contraceptive medication.

Ischemic bowel disease is generally considered a disease of the elderly and usually consists of reversible colopathy. Nonocclusive causes of ischemic colitis include low-flow states due to cardiac dysfunction and hypovolemia and use of certain medications including progestational medication. We report 2 cases of ischemic colitis in young women. The first one occurred in a young patient who developed three consecutive episodes of ischemic colitis during her pregnancy, whereas the second woman presented with ischemic colitis in relation with the estrogen use. Each episode had a favorable outcome. Having ruled out an infectious cause, or a low blood flow state and in the absence of known thrombogenic disease, we hypothesized the etiology of these ischemic episodes to a high level of circulating estrogens due to pregnancy in the first case and oral contraceptive medication in the second. Physicians treating hemorrhagic colitis in young women should consider the use of contraceptive medication containing estrogens or pregnancy as possible causes.

[Repetitive acute pancreatitis in a late-diagnosed cystic fibrosis: prevention of relapses by octreotide in the long term]. / Poussées à répétition de pancréatite aiguë dans une mucoviscidose à révélation tardive: prévention par octréotide au long cours.

We report on the case of a 35 year-old woman who was initially admitted for acute pancreatitis in october 1995. The patient was suffering from asthma (since childhood) and diffuse abdominal pain (since adolescence). The diagnosis of cystic fibrosis was made fortuitously during a sterility evaluation. After extensive etiological screening the acute pancreatitis was considered to be a manifestation of the cystic fibrosis. Despite therapy with pancreatic enzymes, the patient continued to suffer from chronic abdominal pain. High intake of analgesics was required. Until December 1995, the patient was repeatedly admitted for episodes of acute pancreatitis. In January 1996, we initiated a preventive treatment with subcutaneous octreotide between 100 and 200 microgram, three time a day. Thereafter, there were fewer episodes of pancreatitis and the consumption of analgesics decreased. Side effects of octreotide were intermittent diarrhea and development of cholelithiasis that was complicated by biliary migration in November 1998. In June 1999, the prolonged-release form of the molecule was given without modification of the efficacy.

[Strong opioids for chronic non-cancer pain]. / Les opioïdes forts dans les douleurs chroniques non cancéreuses.

A CHALLENGING SITUATION: A number of patients experiencing chronic noncancer pain are unsatisfied with standard treatment modalities. This raises the question of whether there may be a place for strong opioids in the management of these patients. Randomised placebo-controlled trials of strong opioids generated rather disappointing results in this type of pain. Observational studies have indicated that strong opioids may improve comfort and function in some patients with intractable nociceptive or neuropathic pain. However, opioids may be ineffective in others and intolerable side effects, heightened pain and functional impairment as well as drug addiction may also occur. A PROMISING SOLUTION: Finally, strong opioids do not appear to be the issue to all intractable chronic nonmalignant pain states, but they may be a possible issue to a subset of selected and informed patients who agree on the goals of the treatment and accept regular monitoring.

[Prevention of avoidable iatrogenic disease: when patient safety joins with health care economics]. / Prévention de la iatrogénie évitable: quand la sécurité des malades se conjugue avec les économies de santé.

The prevention of preventable adverse therapeutic events (iatrogenic), especially drug related, is a major medical goal for patients, economics and the community. Its incidence is 5 to 15 per cent of hospitalization days. Preventable iatrogenic is a main problem in terms of public health owing to its human and economic consequences. Prevention of iatrogenic is based on better knowledge of its reality, on well-adapted initial and long-term intensive training of physicians, other healthcare workers and also patients and citizens. A better healthcare system is also needed.

[Multidisciplinary management of hereditary colorectal cancer]. / Prise en charge multidisciplinaire du cancer colorectal héréditaire.

AIM: The aim of this study was to assess the feasibility and success of multidisciplinary approach for the management of hereditary colorectal cancer. MATERIAL AND METHODS: From November 1998 to November 2000, 32 individuals with putative familial/hereditary predisposition to colorectal cancer were investigated for adenomatous polyposis (attenuated or classical familial adenomatous polyposis coli, FAP) or for hereditary nonpolyposis colorectal cancer (HNPCC). Amsterdam criteria (I and II) and Bethesda guidelines were used to select putative HNPCC kindreds. Clinical data including endoscopy, pathological and operative reports as well as family history were collected. Pre- and post-test genetic counseling was offered to at-risk individuals. Genetic testing included microsatellite instability (MSI) and search for germline mutations in the APC, hMSH2 and hMLH1 genes. Immunohistochemistry (IHC) of hMSH2 and hMLH1 protein expression in tumour samples was also performed. RESULTS: 11 APC mutations were characterized, whereas four mutations in HNPCC genes were found in hMSH2 (2) and in hMLH1 (2). MSI and IHC correlated completely for cases with identified pathogenic mutation (100%). CONCLUSION: A thorough evaluation and management of hereditary colorectal requires a multidisciplinary approach. Thus, more mutation carriers can be identified and benefit from appropriate genetic counselling, while non-carrier individuals are relieved from unnecessary surveillance.

Evaluation of the placebo effect and reproducibility of blood pressure measurement in hypertension.

Pharmacologic studies in hypertension often describe blood pressure (BP) reductions in placebo control groups. This placebo effect is currently debated, as it seems to be related to BP measurement methods and as a regression to the mean phenomenon may lead to misinterpretation. Furthermore, data on pulse pressure are lacking. This study was designed to evaluate the placebo effect on BP and to differentiate it from regression to the mean. According to a crossover design, 26 mild-to-moderate hypertensive patients who were treated with placebo or given no treatment were followed-up for 1 month. Clinic and ambulatory BP was assessed at baseline and at the end of each 1-month period. Placebo administration resulted in significant reductions in clinic systolic, diastolic, and mean BP (P < .01), ambulatory 24-h SBP (P < .05), and daytime systolic, diastolic, and mean BP (P < .01, P < .05, P < .01, respectively). No significant differences were noted for pulse pressure and heart rate or between BP values measured at baseline and after 1 month without treatment. Despite a significant correlation between changes in clinic and ambulatory BP, the scatter of individual data suggests that the placebo response observed with one method cannot be systematically extrapolated to the other method. This study conclusively shows the effect of placebo in mild-to-moderate hypertension on both clinic and ambulatory systolic, diastolic, and mean BP, in which it has been shown to differ from the regression to the mean phenomenon. This effect was not observed for pulse pressure or heart rate.

Early detection of pancreatic cancer in patients with chronic pancreatitis: diagnostic utility of a K-ras point mutation in the pancreatic juice.

OBJECTIVE: Point mutations of the K-ras oncogene at codon 12 have been described several months before the onset of pancreatic cancer in isolated cases of chronic pancreatitis (CP). The aim of this study was to evaluate the interest of a prospective follow-up of patients with CP and K-ras mutations at codon 12 in the detection of early pancreatic cancer. METHODS: From February 1996 to March 1998, 36 patients (mean age 52.6 yr, 31 men, five women) with CP (alcoholic: 61.1%, pancreas divisum: 5.6%, autoimmune: 5.6%, unknown origin: 27.7%) were included and then prospectively monitored (median duration of 22 months) for detection of pancreatic carcinoma. K-ras point mutations were examined by two-step polymerase chain reaction combined with restriction enzyme digestion in pancreatic juice collected during endoscopic retrograde pancreatography. RESULTS: Ten patients (27.8%) were positive for K-ras mutation. Patients with and without the mutation were not different with respect to age and sex ratio. K-ras mutations were homogeneously distributed according to the etiology (alcoholic vs nonalcoholic) and morphological characteristics (ductal stricture or mass vs none) of CP. A pancreatic carcinoma was discovered at an invasive stage in two patients, respectively at 7 and 17 months after disclosure of a K-ras mutation, versus none in patients without the mutation (p < 0.02). CONCLUSIONS: Presence of a K-ras gene mutation is not rare in patients with CP and represents an increased risk of developing pancreatic cancer. However, its utility for the detection of early pancreatic cancer remains doubtful in clinical practice.

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

The impact on clinical practice of endoscopic ultrasonography used for the diagnosis and staging of pancreatic adenocarcinoma.

CONTEXT: Endoscopic ultrasonography is considered a highly accurate procedure for diagnosing small pancreatic tumors and assessing their locoregional extension. OBJECTIVE: To evaluate the impact of endoscopic ultrasonography on the management of pancreatic adenocarcinoma in clinical practice. PATIENTS: Sixty-four consecutive patients (mean age 70.5 plus/minus 11.9 years) hospitalized for staging or diagnosis of pancreatic adenocarcinoma were retrospectively (from January 1995 to November 1997) or prospectively studied (from December 1997 to August 1999). SETTING: Group 1 consisted of 52 patients with pancreatic adenocarcinoma which was discovered using computerized tomography scanning and/or ultrasound. Endoscopic ultrasonography was utilized for staging purposes only in patients who were considered to be operable and the tumor to be resectable based on computerized tomography scanning criteria. Group 2 consisted of 12 patients who were diagnosed as having a pancreatic adenocarcinoma using endoscopic ultrasonography whereas computerized tomography scanning and ultrasound was negative. MAIN OUTCOME MEASURES: The impact of endoscopic ultrasonography was analyzed on the basis of the number of patients requiring endoscopic ultrasonography as a staging procedure (Group 1) and by evaluating the performance of endoscopic ultrasonography in determining resectability (Groups 1 and 2) based on the surgical and anatomopathological results. RESULTS: Endoscopic ultrasonography was performed in 20 out of 64 patients (31.3%): 8/52 in Group 1 (15.4%) and all 12 patients of Group 2. Endoscopic ultrasonography correctly assessed an absolute contraindication to resection in 11 cases. Resection was confirmed in 8 of the 9 cases selected by endoscopic ultrasonography. The positive predictive value, negative predictive value and overall accuracy of endoscopic ultrasonography for determining resection were 89%, 100%, and 95%, respectively. CONCLUSIONS: The impact of endoscopic ultrasonography seems especially relevant for the detection of pancreatic tumors after negative computerized tomography scanning, and for the prevention of unnecessary laparotomies as complementary staging after ultrasonography and computerized tomography scanning.