Human papillomavirus does not play a role in the Barrett esophagus: a French cohort.

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053).

A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients.

BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY DESIGN: We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5), thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis.

[Results of a novel real-time PCR, sequence analysis, Inno-LiPA line probe assays in the detection of hepatitis B virus G1896A precore mutation in French blood donors]. / Résultats de trois méthodes pour la détection de la mutation précore G1896A du virus de l'hépatite B chez les donneurs de sang français : PCR temps réel, séquençage et test Inno-LIPA.

AIM: To screen hepatitis B virus (HBV) genotypes and associated basal core promoter (BCP; T1762A/A1764) and precore (PC; A1896) mutations among the 100 HBV surface antigen (HBsAg) positive voluntary blood donors in France. METHODS: HBV genotypes were determined by using direct sequence analysis. Three methods were used to detect G1896A mutation: non-commercial real-time PCR (PCRTR°, line probe assay (InnoLiPA HBV PreCore, INNOGENETICS(®)) and direct sequencing of precore gene. HBV viral load was quantified with two commercial real-time PCR (COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV Test/Roche and Real Time HBV/M2000/Abbott). RESULTS: The mean age of donors was 30 (18-64). Patients were from Africa (42%), Europa (50%), and Asia (8%). HBV/D was the most predominant (37%) genotype followed by HBV/A (31%) and HBV/E (22%). PC and BCP mutants were found in 57% with Inno-LIPA HBV test and 59% with both PCRTR and sequencing methods. A significant difference in the viral load of blood donors with wild and PC mutants was observed with the Taqman Cobas real time PCR (3,19 Log(10) UI/ml versus 4,93 Log(10) UI/ml, p < 0.05). Precore phenotype determination was in agreement with the three PC mutation detection methods in 56% of cases. CONCLUSIONS: Non-Caucasian genotype E was present in the French blood donors. PC mutation was more common than BCP mutations in this study. As HBV infected blood donors were more often asymptomatic carriers, we could speculate that the G1896A mutation may favour the asymptomatic state, supporting previous observations.

Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies.

BACKGROUND: We evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis (CVCrT). PATIENTS AND METHODS: Consecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC. RESULTS: A total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive. CONCLUSIONS: In this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.

Neurinoma of the hypoglossal nerve in the submandibular space: case report and review of the literature.

Neurinomas of the hypoglossal nerve extending extra-cranially are rare; a schwannoma in a 63-year-old woman causing nerve palsy is reported. The tumour presented as a slow-growing mass in the right submandibular space; a surgical approach with transcervical exploration was performed. The post-operative course was uneventful.

[Use of erythropoietin in the treatment of anemia induced by ribavirin/interferon in patients with hepatitis C]. / Traitement de l'anémie des patients atteints d'une hépatite C chronique sous interféron/ribavirine par l'érythropoïétine.

We are presenting 20 patients with hepatitis C, who developed anemia on interferon alpha-2b/ribavirin treatment and were treated with recombinant human c alpha. Median age was 43 years (range 25-72). Four patients received previous treatment. Interferon-alpha-2b was given at six million units three times a week to 10 patients and at three million units three times a week to five patients. PEG-interferon-alpha-2b (80-120 mug/week) was given to five patients. The dose of ribavirin was 800-1200 mg/day (19 patients) and 200 mg/day (one patient with renal failure). Duration of an interferon/ribavirin treatment was 6-12 months. Baseline median hemoglobin was 13.3 g/dl (range 12.2-15.8); median hemoglobin nadir: 9.8 g/dl (range 8.4-11.2). On erythropoietin, the hemoglobin increased to median 11.7 g/dl (range 9.6-12.8). The ribavirin dose had been decreased to 800 mg in four patients, to 600 mg in four patients, to 400 mg in one patient. Thirteen patients responded to interferon/ribavirin treatment, six patients (all genotype 1) did not. Of the 13 initial responders 11 had sustained response, one still under treatment and two patients relapsed. In conclusion, in our patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, erythropoietin was beneficial in the treatment of ribavirin-induced anemia.

[Exposure of distal internal carotid artery through mandibular vertical ramus osteotomy]. / Accesso chirurgico all'arteria carotide interna distale medicante osteotomia mandiobolare verticale.

Exposure of the distal internal carotid artery at the level of the second cervical vertebra required manoeuvers such as division of digastric muscle or mandibular subluxation. These increase the exposure but may not provide adequate access and are associated with significant cranial nerves or temporal mandibular joint complications. Vertical Ramus Osteotomy (VRO) provided access of the internal carotid artery (ICA) up to the base of the skull, with low incidence of cranial nerve injury temporo-mandibular joint (TMJ) pain and no preincision preparation. We report two cases in which vertical division of the mandibular ramus provided access of the ICA up to the base of the skull. Preoperative Duplex Scan examination and in the second case the arteriography revealed ICA preocclusive stenosis within 1.5 cm of the skull base. VRO was performed trouhgh a standard neck incision and miniature titanium plates were used to reapproximate the mandible after vascular procedure. There were no death, cranial nerve injury, mandibular nonunion, malocclusion or TMJ pain. We found that VRO is useful when carotid artery pathology extends beyond the usual field of exposure, avoiding nerve injury or TMJ lesion and requires no additional pre-incision preparation.

[Quantitative antibody analysis: use for the diagnosis of hepatitis C virus chronic infection]. / Analyse quantitative des anticorps dirigés contre le virus de l'hépatite C (VHC): application au diagnostic d'infection chronique par le VHC.

Hepatitis C virus (HCV) infection has been estimated in 600,000 subjects in France, with about 80 % of chronic infection. In the latter, anti-HCV antibodies and viral RNA are found together in patients blood. Today, only the use of polymerase chain reaction (PCR) technology allows the diagnosis of HCV chronic infection, confirmed by a positive PCR. However, PCR is a laborious and cost effective method. The aim of this study was to distinguish HCV chronic infection to past-infection or false reactivity only using the serology testing. Therefore, we looked for a correlation between the results of PCR, using the HCV Cobas Amplicor 2.0 assay, and the level of anti-HCV antibodies, assessed by the AxSYM HCV v.3.0 and expressed in signal/cutoff (s/co) ratio. We found using a panel of 200 sera issued from 181 patients, a significant variation of s/co ratios between PCR positive and negative patients (respectively, 87.76 +/- 27.18 vs 10.13 +/- 13.68 s/co, p < 0.0001), only in non treated or previously treated patients, non HIV coinfected, non renal transplanted or haemodialysis patients. An anti-HCV cutoff value at 34 s/co allows a predictive PCR results with 100 % sensitivity and 93.3 % specificity. Thus, for patients having a s/co equal or over 34, a positive PCR was found in 98.1 % of cases, allowing the diagnosis of HCV chronic infection (positive predictive value). Conversely, in patients with less than 34, HCV chronic infection can be excluded in 100 % of cases (negative predictive value). In conclusion, in most cases, the use of anti-HCV quantitative analysis in the AxSYM HCV v.3.0 assay could avoid PCR testing and facilitate the diagnosis of HCV chronic infection.

[Lymph node metastases in paranasal sinus carcinoma: prognostic value and treatment]. / Metastasi linfonodali nei carcinomi dei seni paranasali: valore prognostico e trattamento.

The purpose of this report is to assess, on the basis of a sizeable study, the prognostic value of lymph node metastases in paranasal sinus carcinoma and, in particular, in squamous cell carcinoma of the maxillary sinus. We have reviewed the charts of 601 cases of paranasal sinus carcinoma between 1970 and 1999. All of the patients were treated surgically, alone or associated with chemotherapy and/or radiotherapy. The maxillary sinus tumors numbered 379 (153 squamous cell carcinomas, 15 undifferentiated carcinomas, 94 adenoid cystic carcinomas, 19 adenocarcinomas, 98 mesenchymal tumors and rare forms) and the ethmoidal tumors were 222 (117 adenocarcinomas, 27 squamous cell carcinomas, 16 adenoid cystic carcinomas, 13 undifferentiated carcinomas, 49 other histological forms). Lymph node metastases in ethmoidal tumors were rare, with the exception of undifferentiated carcinoma (46.1%). The percentages of metastatic squamous cell carcinoma of the maxillary sinus upon presentation were: T2 15.5%, T3 7%, and T4 4%. All these patients underwent lymph node excision. The metastases successive to treatment of the primary tumor were: T2 16.9%, T3 8.8%, and T4 12%. 75% of these late metastases occurred contemporaneously with a recurrence of T and only 5 (25%) constituted the single reawakening of disease; four of these patients underwent neck surgery and were cured operatively. One had fixed, inoperable metastases. The NED survival rate at least two years after T therapy in patients free from metastases was 50.4%, against 25% in those with initial or distant metastases (T2 72.9% vs. 30.4%, T3 37.5% vs. 22.2%, and T4 28.6% vs. 0%). In conclusion, squamous cell carcinomas of the maxillary sinus which have extended to the oral cavity (T2) show greater lymph node propagation than those of the superoposterior portion (T3-T4). The presence or successive appearance of lymph node metastases indicates elevated malignancy of the tumor, with a very negative prognosis. N, however, is rarely the cause of death for these patients. Prophylactic lymph node excision in N0 patients is therefore not indicated.

Surgical techniques in the treatment of pleomorphic adenoma of the parotid gland: our experience and review of literature.

This paper presents a retrospective study carried out on a sample of 100 patients affected by pleomorphic adenoma of the parotid gland and treated at the Department of Maxillofacial Surgery at the University of Rome "La Sapienza" between January 1, 1989 and December 31, 1997. For the diagnosis of this neoformation, cytological tests were performed on material taken from the neoformation using fine needle aspiration and ultrasound scan. In some selected cases, a CT examination of the head and neck with medium contrast or Nuclear Magnetic Resonance (NMR) was carried out. This study sets out to examine the most suitable treatment to be followed for the removal of the pleomorphic adenoma of the parotid gland. In 56 cases the patients underwent a superficial, conservative parotidectomy. Forty one patients had a total parotidectomy with the facial nerve left intact and one patient had a total parotidectomy where the marginal mandibular nerve of the facial nerve was damaged. The remaining two patients involved in the study were suffering from a recurrent pleomorphic adenoma and in these two cases a total parotidectomy was performed where the facial nerve was killed. The removal of the cranial nerve VII in these patients proved necessary because the nerve fibers had adhered to the surrounding scar tissue of the tumor, either after previous surgery or due to repeated chronic phlogosis of the gland.

Celiac plexus block: injectate spread and pain relief in patients with regional anatomic distortions.

BACKGROUND: The success of the neurolytic celiac plexus block, despite different approaches and methods used, depends on adequate spread of the injectate in the celiac area. This retrospective study was conducted to evaluate the patterns of alcohol spread and pain relief in patients with cancer or therapy-related anatomic distortion of the celiac area. METHODS: From 177 cancer patients who underwent computed tomography (CT)-guided single-needle neurolytic celiac plexus block via an anterior approach, a radiologist, blind to the aim of the study, retrospectively selected 105 patients with abnormal anatomy of the celiac area as judged by CT images obtained before the block. To evaluate CT patterns of neurolytic (mixed with contrast) spread, the celiac area was divided on the frontal plane into four quadrants: upper right and left and lower right and left, as related to the celiac artery. Results were expressed as the number of quadrants into which contrast spread, ie., four, three, two, or one quadrants with contrast. The patterns of contrast spread according to the number of quadrants with anatomic distortion were analyzed. Patient assessment by visual analog scale was reviewed to evaluate the degree of pain relief. Pain relief 30 days after block was considered long-lasting. Pain relief at 30 days after block was analyzed according to the number of quadrants with contrast. RESULTS: Overall, four, three, two, and one quadrants with contrast were observed in 9 (8%), 21 (20%), 49 (47%), and 26 (25%) patients, respectively. An inverse correlation was observed between the number of quadrants with anatomic distortion and the number of quadrants with contrast (P < 0.001). Long-lasting pain relief was noticed in nine of nine patients (100%; 95% confidence interval, 66-100) with contrast in four-quadrants, and in 10 of 21 patients (48%; 95% confidence interval, 26-70) with contrast in 3 quadrants (P < 0.01). None of the 75 patients with contrast in two quadrants or one quadrant experienced long-lasting pain relief. CONCLUSIONS: These findings suggest that, using the single-needle anterior approach, the neurolytic spread in the celiac area is highly hampered by the regional anatomic alterations. It also appears that only a complete (four quadrants) neurolytic spread in the celiac area can guarantee long-lasting analgesia, and that this picture may be obtained in a very limited fraction of patients with regional anatomic alterations.

Abrikossoff's tumor.

Abrikossoff's tumor is a disease that more commonly affects the oral cavity but can also occur at other sites. It develops between the second and sixth decades of life, more frequently among women and blacks. The neoplasm can affect all parts of the body. The head and neck areas are affected in 45% to 65% of cases and of these, 70% are located interorally (tongue, oral mucosa, hard palate). The benign form shows polygonal cells with granular, eosinophilic cytoplasm and small nuclei. The malignant form, however, is associated with a high mitotic index and pleomorphic cellular tissue. The clinical aspect of the neoformation is a swelling covered by mucus of normal appearance. Studies of the neoformation show that in addition to the objective examination, further instrumental research is necessary, i.e., with nuclear magnetic resonance or computed tomography with contrast CT scan. However, the only examination that can confirm the clinical diagnosis is the histological examination. The only treatment for Abrikossoff tumor is surgery. The surgical treatment provides for an extirpation of the neoformation with the overhanging mucus and the underlying periosteum. In this work, the authors discuss a case of Abrikossoff tumor affecting the mucus of the right side of the hemipalate in a 53-year-old patient and present a review of the literature.

Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer.

Some years ago it was proved that a good percentage of small cell lung cancers, classified among cancers of the APUD system, produces somatostatin receptors that can be detected in vivo by scintigraphy with 111In-DTPA-octreotide. With the method in the whole body it is possible to identify the principal neoformation and the probable metastases. The authors present a study of 21 patients afflicted with small cell lung cancer diagnosed histologically. The study, carried out between January 1995 and December 1997, compared the radiologic iconography of the CT scan with the scintigraphic map obtained by a planar scintigraphy and in SPECT 1, 4 and 24-hr after iv injection of 110 MBq of 111In-DTPA-octreotide. The comparison was made with reference to the principal neoplasm and probable metastases. A scintigraphic study, a CT of restaging and a follow-up, done after 3 and 6 months of chemotherapy, on 15 patients with cancer that produces somatostatin receptors proved that the neoplasm sometimes regresses and sometimes progresses. In the latter case, it is possible to identify cerebral, mediastinal and hepatic metastases with the administration of 200 microg of octreotide 3 times a day for 7 days before the scintigraphy. In fact, the administration lowers background activity. The authors concluded that scintigraphy with 111In-DTPA-octreotide plays an important part in the study of patients afflicted with small cell lung cancer. Scintigraphy identifies the subgroups of patients who can be cured with somatostatin analogues together with chemotherapy. Scintigraphy presents a good sensibility in the re-staging and in the follow-up of patients who are treated, even though it is difficult to identify subdiaphragmatic metastases where liver, spleen and kidney show an increase in 111In-DTPA-octreotide.

Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit.

OBJECTIVE: Our study aimed at evaluating the pharmacokinetic, cardiovascular, and metabolic effects of high-dose verapamil continuous intravenous infusion in cancer patients. DESIGN: Prospective clinical and pharmacokinetic study. SETTING: Intensive care unit of a Cancer Research Institute. PATIENTS: Nine patients (age range 31 to 57 yrs) with progressive cancer disease and without cardiovascular, renal, or hepatic dysfunctions. INTERVENTIONS: After a loading dose (0.15 mg/kg followed by 12 hrs of continuous intravenous infusion at 0.20 mg/kg/hr), the infusion rate of verapamil was increased every 24 hrs (0.25, 0.30, 0.35, and 0.40 mg/kg/hr). The highest rate was maintained for 48 hrs. Doxorubicin was given from the 60 th to the 108 th hr. Hydrochlorothiazide (25 mg/day) and potassium (36 mmol/day) were given orally. Altogether, 17 courses were completed. MEASUREMENTS AND MAIN RESULTS: Steady state concentration (C(SS) and systemic clearance of verapamil and nor-verapamil (active metabolite) for each infusion rate were calculated. Mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), PR, QT and QTc intervals, and left ventricular ejection fraction (LVEF) were measured, as well as daily body weight, blood glucose and potassium. C(SS) of verapamil and nor-verapamil increased more than proportionally to the infusion rate (p<.001). Systemic clearance of verapamil decreased over the range of the infusion rate (p<.005). MAP and HR decreased at the 12th hr (p<.001) and then plateaued. CVP increased (p<.01). The relationship between MAP, HR, CVP, and verapamil plasma concentrations was significant (r2 = .25, .14, and .35, respectively; p<.0001). LVEF did not change. Six patients (11 courses) developed junctional rhythm. Three patients (six courses) showed a PR interval increase (p<.05). Patients with junctional rhythm had higher Css of verapamil (p<.009). Overall, QT and QTc intervals increased (p<.01). A linear relationship was observed between verapamil plasma concentrations and QT intervals (r2 = .09, p<.01). Cardiovascular side effects did not determine treatment withdrawal in any patient. Body weight, blood glucose, and potassium did not show significant changes. CONCLUSIONS: Our data suggest a capacity-limited clearance of high-dose verapamil. In the absence of heart disease, following a step by step increase of the dosage, the high plasma verapamil concentrations (617 to 2970 ng/mL) produce frequent but well tolerated hemodynamic and electrocardiogram changes.

Temporomandibular joint biomechanical restrictions: the fluid and synovial membrane.

The authors analyze the functions of the synovial membrane and the chemical-physical properties of synovial fluid. In particular they evaluate the role played by synovial fluid in the complex mechanism of the temporomandibular joint. Every single part that belongs to the temporomandibular joint, together with the stomatognathic apparatus, plays a specific and particular role according to the dynamics and to the preservation of the correct temporomandibular joint physiology. The physiological postural and functional relationship between the various parts of the temporomandibular joint is guaranteed by a number of biomechanical restrictions that lead and influence the regular execution of the articular movements. The most involved biomechanical restrictions in the temporomandibular joint are the temporomandibular ligament, the lateral disc ligament, the bilaminar zone or retrodiscal tissue, the synovial membrane, and the synovial fluid.

Pulmonary involvement in tuberous sclerosis complex: presentation of a case.

A clinical case of a pulmonary involvement in Tuberous Sclerosis Complex is reported. This rare involvement (1%) is characterized by either interstitial disease or bullae; therefore, pneumothorax is likely to happen in lung parenchyma. Furthermore this complication induces a progressive serious respiratory failure until the death of the patient.

Randomized trial of 5-fluorouracil and high-dose folinic acid with or without alpha-2B interferon in advanced colorectal cancer.

We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, to either a combination chemotherapy of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or the same regimen plus interferon. Between January 1990 and March 1992, 100 untreated patients (PTS) with advanced colorectal cancer, 53 men and 47 women, with an ECOG performance status (PS) of < or = 3, were randomized to either HDFA 200 mg/m2 iv bolus and 5FU 370 mg/m2 in 15-min iv infusion days 1-5 every 4 weeks (arm A), or the same chemotherapy plus IFN 3 x 10(6) IU subcutaneously three times a week in chemotherapy intervals (arm B). A total of 97 PTS are evaluable for response, toxicity, and survival; 3 PTS are not evaluable in arm B for major protocol violations. PTS characteristics were well balanced in both arms for age (median, 64 years), disease-free survival, and disease site. ECOG PS was 0 in 28% of PTS in arm A and in 13% in arm B. Response rates were as follows: arm A, 40%; and arm B, 23%. Median time to failure was as follows: 10.2 months arm A versus 9 months arm B. Median survival was as follows: 13.3 months arm A versus 10.9 months arm B. Grade 3 haematological toxicity was 9% of PTS in both arms. Gastrointestinal toxicity was as follows: 17% arm A versus 22% arm B. The cost of drugs expressed per m2/month was $60 in arm A and $390 in arm B. The results show that IFN at the schedule and doses employed adds no benefit to the combination of 5FU/HDFA.

Mixed cryoglobulinemia and hepatitis C virus.

BACKGROUND: Mixed cryoglobulinemia (MC) is frequently associated with clinical and biological evidence of liver disease and has recently been reported in cases of hepatitis C virus (HCV) infection. The aim of this study was to assess prospectively in a large series of MC patients: (1) the prevalence of HCV markers (anti-HCV antibodies and HCV RNA in serum and cryoprecipitate); (2) the main clinical, biologic and liver histologic features in patients with or without HCV infection. PATIENTS: One hundred fifteen consecutive unselected MC patients were studied: 45% had well-defined underlying diseases ("nonessential" MC). Fifty-five percent with no cause of MC were considered to have "essential" MC and were subjected to in-depth examination. METHODS: Patients were considered to have MC if two successive determinations of their serum cryoglobulin level were above 0.05 g/L. Anti-HCV antibodies (Ab) were detected in all patients by second-generation tests (ELISA, RIBA). We also looked for HCV RNA sequences amplified by polymerase chain reaction (PCR) in the sera and cryoprecipitates of 39 patients; HBs antigen, anti-HBs Ab and anti-HBc Ab in all patients; and HBV DNA in 20 sera and 17 cryoprecipitates. Quantitative HCV Ab and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Clinical features were recorded retrospectively for each patient. Liver biopsies from 23 anti-HCV Ab-positive and 7 anti-HCV Ab-negative patients were examined histologically, with qualitative and quantitative analysis. RESULTS: Anti-HCV Ab were found in 47/115 (41%) patients by ELISA and RIBA: 33/63 (52%) essential MC and 14/52 (27%) nonessential MC. Among the 63 essential MC patients, the 33 anti-HCV Ab-positive (Group 1) were compared to the 30 anti-HCV Ab-negative patients (Group 2). Group 1 patients had more cutaneous involvement (Raynaud's phenomenon, purpura, livedo, distal ulcers, or gangrenous changes) (17 versus 5: p = 0.004), higher alanine aminotransferase levels (110 +/- 22 versus 41 +/- 10 IU; p < 0.005), higher serum cryoglobulin levels (0.35 +/- 0.07 versus 0.12 +/- 0.04 g/L; p = 0.01), lower CH50 (28 +/- 3 versus 44 +/- 2 CH50/mL; p = 0.0001) and lower C4 levels (0.20 +/- 0.02 versus 0.29 +/- 0.03 g/L; p < 0.04). The prevalence of HBV serum markers was low in both groups, and HBV DNA was never detected in any of the sera and cryoprecipitates tested. HCV RNA sequences were detected in 10/16 (63%) sera and 12/16 (75%) cryoprecipitates from Group 1 patients, whereas they were not in the sera or cryoprecipitates from 23 Group 2 patients. Using quantitative PCR, HCV RNA in cryoprecipitates was concentrated 20 to 100 times despite the absence of significant anti-HCV Ab concentration in these samples. Histologic examination of liver biopsies revealed a spectrum of lesions ranging from chronic active hepatitis to cirrhosis, but Knodell's score did not differ between the groups. CONCLUSION: (1) About 50% of the essential MC patients had anti-HCV Ab, and these patients had more severe cryoglobulinemia-associated clinical and biological signs; (2) HCV RNA sequences were found in the large majority of sera and cryoprecipitates from patients with essential MC and anti-HCV Ab and were more concentrated in cryoprecipitates than in supernatants. These results suggest a role for HCV in the pathogenesis of MC and indicate that many cases of essential MC may be secondary to HCV infection and thus nonessential.