Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas.

To clarify the relationships between marginal zone lymphomas (MZLs) and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (WM/LPLs), immunoglobulin heavy chain variable gene (IGHV) features were analyzed and the occurrence of MYD88 L265P mutations was identified in a series of 123 patients: 53 MZLs from the spleen (SMZLs), 11 from lymph nodes (NMZLs), 28 mucosa-associated lymphatic tissue (MALT) lymphomas and 31 WM/LPLs. SMZLs were characterized by overrepresentation of IGHV1-2 gene rearrangements with a canonical motif, without selection pressure and with long CDR3 segments. NMZLs had increased frequencies of IGHV3 genes. The IGHV gene was unmutated in most cases, often with long CDR3 segments. MALT lymphomas were usually associated with a mutated IGHV gene, but with the absence of selection pressure. WM/LPLs were associated with an IGHV3-23 overrepresentation and high IGHV mutation rate, with features of selection pressure and short CDR3 segments. MYD88 L265P mutations were almost restricted exclusively to WM/LPL patients. Taken all diagnoses together, all patients with MYD88 L265P mutations had an immunoglobulin M peak and almost all patients except one had bone marrow infiltration. These results demonstrate that the history of antigen exposure of the four entities studied was different and MYD88 L265P was specifically associated with WM/LPLs. WM/LPL may thus be functionally associated with constitutive nuclear factor-κB activation.

Assisted reproductive technology and ovarian cancer.

Ovarian cancer has the highest mortality among all gynaecological cancers, being multiparity and oral contraceptive use the most important protective factors. According to both the "incessant ovulation" and "increased gonadotrophin" theories, fertility drugs might have an association with the development of ovarian cancer, as has been reported by some studies. However, infertility and nulliparity may act as confounding factors and most studies regarding this issue are hampered by methodological limitations. It seems that female infertility may be associated with a modest increase in ovarian cancer risk in those patients who remain nulligravid despite long periods of unprotected intercourse. Globally, most studies are reassuring in not showing a link between the use of fertility drugs and an increased risk of ovarian cancer. Nonetheless, further research in well-designed studies is warranted.

Predictive baseline criteria of primary therapeutic failure in chronic hepatitis C genotype 1.

BACKGROUND AND AIMS: more than half of patients with genotype 1 chronic hepatitis C (CHC) do not achieve a sustained viral response (SVR) to current antiviral therapy due to primary non-response, relapse or intolerance. Factors related to each of these unfavorable outcomes are different and the last two may be partially prevented. Our aim was to identify basal criteria to predict the risk of primary failure. PATIENTS AND METHODS: we included 251 consecutive patients (152 males) from a single centre, infected with HCV genotype 1 and not previously treated. SVR was achieved in 141 patients and primary failure in 110. RESULTS: high vs. low viral load (> 400,000 IU/mL, OR = 6.17; 95% CI: 2.50-15.23), high serum GGT (> 60 IU/mL, OR = 4.25; 95% CI: 2.49-7.24), low serum cholesterol ( < 178 mg/dL, OR = 2.93; 95% CI: 1.75-4.92) and older age (> 47 yrs., OR = 1.79; 95% CI: 1.08-2.96) were associated to the risk of primary failure in the lineal logistic regression analysis. From the 58 patients carrying all the first three negative criteria, 46 (79.3%) were primary non-responders. CONCLUSIONS: the negative basal profile identified in this study is based on easily available data and provides information about the risk of primary therapeutic failure, and may help to decide whether antiviral therapy should be offered to a single patient.

Predictive baseline criteria of primary therapeutic failure in chronic hepatitis C genotype 1

Background and aims: more than half of patients with genotype 1 chronic hepatitis C (CHC) do not achieve a sustained viral response (SVR) to current antiviral therapy due to primary non-response, relapse or intolerance. Factors related to each of these unfavorable outcomes are different and the last two may be partially prevented. Our aim was to identify basal criteria to predict the risk of primary failure. Patients and methods: we included 251 consecutive patients (152 males) from a single centre, infected with HCV genotype 1 and not previously treated. SVR was achieved in 141 patients and primary failure in 110. Results: high vs. low viral load (> 400,000 IU/mL, OR = 6.17; 95% CI: 2.50-15.23), high serum GGT (> 60 IU/mL, OR = 4.25; 95% CI: 2.49-7.24), low serum cholesterol (< 178 mg/dL, OR = 2.93; 95% CI: 1.75-4.92) and older age (> 47 yrs., OR = 1.79; 95% CI: 1.08-2.96) were associated to the risk of primary failure in the lineal logistic regression analysis. From the 58 patients carrying all the first three negative criteria, 46 (79.3%) were primary non-responders. Conclusions: the negative basal profile identified in this study is based on easily available data and provides information about the risk of primary therapeutic failure, and may help to decide whether antiviral therapy should be offered to a single patient(AU)

Oscillations in serum ferritin associated with antiviral therapy in chronic hepatitis C.

BACKGROUND: Hyperferritinemia is often found in patients with chronic hepatitis C (CHC) and is predictive of poorer response to antiviral therapy. OBJECTIVE: To investigate changes in ferritinemia during and after antiviral therapy. PATIENTS AND METHODS: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.5 years +/- 10.1) before and during antiviral therapy, and six months post-treatment in all 154 patients with undetectable serum HCV-RNA after therapy completion. RESULTS: Baseline serum ferritin was higher in patients with primary therapeutic failure than in those reaching sustained viral response (330 +/- 291 ng/mL vs. 211 +/- 192 ng/mL, p = 0.002). Serum ferritin transiently increased during therapy from baseline (257 +/- 242 ng/mL vs. 875 +/- 630 ng/mL, p < 0.001). Six months after finishing therapy, serum ferritin decreased under baseline values both in sustained responders (117 +/- 102 ng/mL vs. 211+/- 192 ng/mL, p < 0.001) and, to a lesser extent, in relapsers (217 +/- 174 ng/mL vs. 257 +/- 221 ng/mL, p = 0.047). CONCLUSIONS: Baseline serum ferritin may predict response to antiviral treatment in chronic hepatitis C. Combined antiviral therapy induces a marked increase in serum ferritin that falls below baseline values after sustained viral response, suggesting that the cause of hyperferritinemia in many patients is HCV infection itself rather than iron overload.

Oscilaciones de la ferritina sérica asociadas al tratamiento antiviral en la hepatitis crónica por virus C / Oscillations in serum ferritin associated with antiviral therapy in chronic hepatitis C

Antecedentes: la hiperferritinemia es frecuente en los enfermoscon hepatitis crónica C (HCC) y reduce las probabilidades derespuesta al tratamiento antiviral.Objetivo: investigar las variaciones de la ferritina sérica durantey después del tratamiento y su relación con la respuesta al mismo.Pacientes y métodos: la ferritina sérica se ha medido en262 enfermos con HCC (163 hombres, edad media 48,5 años ±10,1) antes y durante el tratamiento antiviral, y a los 6 meses definalizado en los 154 enfermos con viremia indetectable al finaldel tratamiento.Resultados: la ferritina sérica basal era más alta en enfermoscon fracaso terapéutico primario que en los que consiguieron respuestaviral sostenida (RVS) (330 ± 291 ng/ml vs. 211 ± 192ng/ml, p = 0,002). La ferritina sérica aumentó transitoriamentedurante el tratamiento (257 ± 242 ng/ml vs. 875 ± 630 ng/ml, p< 0,001). La ferritina sérica descendió a valores inferiores a losbasales seis meses después de finalizado el tratamiento en los pacientescon RVS (117 ± 102 ng/ml vs. 211± 192 ng/ml, p <0,001) y, en menor grado, en los que sufrieron recidiva viral (217± 174 ng/ml vs. 257 ± 221 ng/m, p = 0,047).Conclusiones: una ferritina sérica basal elevada se asocia conmayor riesgo de fracaso terapéutico en la HCC. El tratamientoantiviral induce un marcado incremento de la ferritina sérica quevuelve a valores por debajo de los basales en los enfermos que obtienenRVS. Esto sugiere que la causa de hiperferritinemia en lamayoría de los enfermos es la propia infección por VHC y no lasobrecarga de hierro(AU)

Background: hyperferritinemia is often found in patients with chronic hepatitis C (CHC) and is predictive of poorer response to antiviral therapy. Objective: to investigate changes in ferritinemia during and after antiviral therapy. Patients and methods: serum ferritin levels were measured in 262 CHC patients (163 males, mean age 48.5 years ± 10.1) before and during antiviral therapy, and six months post-treatment in all 154 patients whit undetectable serum HCV-RNA after therapy completion. Results: baseline serum ferritin was higher in patients with primary therapeutic failure than in those reaching sustained viral response (330 ± 291 ng/mL vs. 211 ± 192 ng/mL, p = 0.002). Serum ferritin transiently increased during therapy from baseline (257 ± 242 ng/mL vs. 875 ± 630 ng/mL, p < 0.001). Six months after finishing therapy, serum ferritin decreased under baseline values both in sustained responders (117 ± 102 ng/mL vs. 211± 192 ng/mL, p < 0.001) and, to a lesser extent, in relapsers (217 ± 174 ng/mL vs. 257 ± 221 ng/mL, p = 0.047). Conclusions: baseline serum ferritin may predict response to antiviral treatment in chronic hepatitis C. Combined antiviral therapy induces a marked increase in serum ferritin that falls below baseline values after sustained viral response, suggesting that the cause of hyperferritinemia in many patients is HCV infection itself rather than iron overload(AU)

[Results of the treatment of chronic hepatitis C genotype 4--a comparative analysis with genotype 1]. / Resultados del tratamiento de la hepatitis crónica por VHC genotipo 4. Un análisis comparativo con el genotipo 1.

INTRODUCTION: nearly all the data on the efficacy of combined antiviral therapy on chronic hepatitis C genotype 4 have been obtained in countries of Middle East. Genotype 4 is quite unusual in Spain. We report our experience in a group of Spanish patients treated with homogeneous criteria. PATIENTS AND METHODS: between 2001 and 2007 we have treated 30 patients with chronic hepatitis C genotype 4 (20 males) with pegylated Interferon alpha-2b (26 cases) or alpha-2a (4 cases) combined with ribavirin at a weight-adjusted dose. Results of therapy are known in all patients and liver biopsy is available in 24 cases. RESULTS: ten patients (33.3%) obtained sustained viral response (SVR: HCV-RNA undetectable in blood 6 months after the end of therapy), 12 were primary non-responders, 4 relapsed after reaching undetectable HCV-RNA at the end of therapy and 4 interrupted the treatment due to severe adverse events. These results are very close to those obtained in 355 patients infected with HCV genotype 1. CONCLUSION: HCV genotype 4 should be considered as "difficult to treat". The better results of therapy in other geographical areas (Middle East) may be due to a different distribution of the subtypes of HCV genotype 4.

Subgenotype diversity of hepatitis B virus American genotype F in Amerindians from Venezuela and the general population of Colombia.

The objective of this study was the evaluation of the genetic diversity found in HBV circulating among Venezuelan Amerindians and the general population in Colombia. Phylogenetic analysis of the S region in 194 isolates showed that genotype F is highly predominant in Colombia and Venezuela. This might be related to the genetic background of the population. F3 is the main subgenotype which circulates in both countries. Phylogenetic analysis of 61 complete genome sequences of HBV American genotypes confirms the presence of two genotypes F and H, and 4 F subgenotypes. In Venezuela, subgenotypes F1, F2, and F3 circulate in East and West Amerindians, while only F3 was found among South Amerindians. Japreira community derived from Yucpa Amerindians around 150 years ago. However, several Japreira HBV sequences were forming a clade that can be classified as subgenotype 2b, differing from Yucpa sequences that belong mainly to subgenotype F3. The apparent absence of correlation between the phylogenetic groupings of HBV isolates with the ethnical origin in aboriginal populations might be suggesting a recent origin of HBV American subgenotypes, or a genetic drift effect.

Utilidad de la determinación de la fracción I de la Troponina cardíaca (cTnI), en el diagnóstico de la muerte súbita de origen cardíaco en autopsias forenses / Usefulness of cardiac troponin I (cTnI) in the diagnosis of sudden cardiac death in forensic autopsies

Objetivo: Evaluar la utilidad práctica del análisis de la concentración de Troponina I (cTnI), en el diagnóstico de rutina de las muertes de origen cardíaco en muestras de sangre periférica de autopsias forenses, y compararlas con las cifras de Mioglobina y fracción MB de la Creatin kinasa en el mismo tipo de muestras. Material y métodos: Se han estudiado 97 autopsias forenses realizadas en el Servicio de Patología del Instituto de Medicina Legal de Alicante (IMLA). En cada caso se realizó una toma de muestra de sangre periférica que fue posteriormente analizada mediante inmunoanálisis semiautomatizado de micropartículas enzimáticas (MEIA) con un equipo Axsym de Abbott. Las causas de muerte fueron agrupadas en 6 grupos de acuerdo al siguiente esquema: 1) muertes de origen cardiaco (n= 42), 2) muertes de origen traumático (n=19), 3) muertes de tipo asfíctico (n=12), 4) muertes naturales de causa no cardiaca (n=8), 5) miscelánea (n=6) y 6) Muerte traumática con contusión torácica (n=10). Los datos fueron analizados mediante un paquete estadístico SPSS. Resultados: Los niveles medios de cTnI fueron significativamente mayores en los grupos de causas de muerte cardiaca, pero también lo fueron en el grupo de traumatismo con contusión cardiaca, lo que plantea problemas de diagnóstico diferencial entre ambas patologías. Conclusiones: La determinación de cTnI se ha mostrado más eficaz que la CK-MB y la Mioglobina en el diagnóstico de la muerte súbita de origen cardíaco. Sin embargo, la existencia de una elevación de los niveles medios de este marcador en los casos de traumatismo torácico intenso limita su utilidad diagnóstica, en estas situaciones

Objetives: To evaluate practical usefulness of cardiac Troponin analysis (cTnI) in peripheral blood levels, in order to improve diagnosis of sudden cardiac death in routine forensic cases. Comparing these levels with Myoglobin and MB-CK blood levels in the same type of samples. Material and methods: We have studied 97 medico legal autopsies performed in the Pathology Service of the Institute of Legal Medicine (Alicante). In every case we analyzed sample of serum from peripheral blood (femoral), by Microparticle Enzyme Immunoassay (MEIA) Axsym system (Abbott Diagnostics). Causes of death were classified into 6 groups according: 1) Death of cardiac origin (n=42); 2) Traumatic deaths (n=19); 3) Death by asphyxia (n=12); 4) Natural deaths of non-cardiac origin (n=8); 5) Miscellaneous group (n=6), and 6) Traumatic death with Thoracic trauma (n=10). Data was analysed by means of SPSS 14.0 statistical software program (SPSS Inc, 2005). Results: cTnI levels were significantly high in cases of sudden cardiac death, but it were also high in the group of thoracic trauma, which could raise diagnosis problems between these groups, as was shown previously in the literature. Conclusions: The determination of cTnI is more efficient than CKMB and Myoglobine in the diagnosis of sudden cardiac death. However, the elevation of mean levels of this marker in cases of severe thoracic traumatism limits its diagnostic usefulness in these situations

Benign rectovaginal fistulas: management and results of a personal series.

BACKGROUND: Treatment of benign rectovaginal fistula has a high failure rate and entails difficult decisions. The purpose of this retrospective study was to clarify the concepts which may improve its management. METHODS: Between 1983 and 2004, 46 consecutive women of median age 41 years were treated by the same surgeon. Etiology of simple fistulas was iatrogenic (n=6), obstetric (n=4) and septic (n=3). Complex fistulas were due to inflammatory bowel diseases (IBD) (n=18, 11 pouchvaginal) or were iatrogenic (n=9), actinic (n=5) or septic (n=1). Surgical techniques included endorectal or vaginal advancement flaps, fistulectomy and sphincteroplasty, vaginal/rectal closure and epiploplasty, restorative proctectomy and restorative proctocolectomy. In 20 patients, a diverting stoma was performed as a single procedure or concomitant to the curative attempt. RESULTS: Overall, 33 of the 39 fistulas (85%) treated for cure healed, including all simple fistulas and 20 complex fistulas (8 iatrogenic, 3 actinic, 2 ulcerative colitis without restorative proctocolectomy; 5 pouch vaginal; 1 septic; 1 Crohn's disease) (p=0.009). The first operation for the fistula was curative in 20 of 39 fistulas, including 10 of 13 simple and 10 of 26 complex fistulas (p=0.023). There was no significant age difference between cured and not-cured patients. CONCLUSIONS: Simple versus complex fistulas is the most determinant factor for healing. In IBD fistulas, ulcerative colitis shows better prognosis than Crohn's disease. For complex fistulas, a temporary diverting stoma seems necessary.

[Economics, health, and health care]. / Economía, salud y asistencia sanitaria.

Since the seventies the growing of sanitary expenses has become the first worry for our authorities and the seeking of solutions has brought the presence of economists to solve the health problems. Therefore the health economy studies the production and distribution of health and sanitary attention in two senses: one like a discipline (usually located in universities and publications in the area of economy) and another one to the resolution of health problems and care, favouring interdisciplinary cooperation and its application to management. When speaking about the relation ship between economy and health, it is necessary to consider three areas: first that of basic concepts in economy: demand, offer, elasticity, market faults and state intervention in economy. The second aspect goes to the specific characteristics of sanitary care from economic perspective and the application of economic concepts to health field. And finally the third one is the field of the most important techniques of economic evaluation for sanitary programs and the analysis of sanitary systems reforms in some countries.

Ultrastructural and immunohistochemical characterization of the so-called giant multinucleate cells in cutaneous collagenomas.

AIMS: This study was undertaken to compare the histopathological, immunohistochemical and ultrastructural features of the so-called giant multi nucleate cells in cutaneous collagenomas: giant-cell collagenoma and solitary sclerotic fibroma. METHODS AND RESULTS: We studied four collagenomas: one giant-cell collagenoma and three solitary sclerotic fibromas. All the cases showed an indolent clinical presentation and were histologically constituted by a well-demarcated dome-shaped proliferation of coarse collagen bundles with a varying number of interspersed giant multinucleate cells and stellate mononuclear cells. The immunohistochemical study on paraffin sections revealed that neoplastic cells in both collagenomas were vimentin and CD34-positive, whereas FXIIIa was only expressed in solitary sclerotic fibromas. In regard to the so-called giant multinucleate cells, we have ultrastructurally found that these cells were 'real' multinucleate cells in giant-cell collagenoma, whereas in solitary sclerotic fibromas they consisted of closely packed aggregates of individual stellate mononuclear cells. Moreover, perinuclear cisternae focally containing finely textured material of moderate density were unexpectedly found in giant cells of giant-cell collagenoma, a finding which was not observed in solitary sclerotic fibromas. Additionally, a characteristic cell-cell interaction between tumour cells and mast cells was encountered in all collagenomas. CONCLUSIONS: This study supports a distinctive immunohistochemical and overall ultrastructural profile of giant multinucleate cells in giant-cell collagenoma and solitary sclerotic fibroma, which suggests a different pattern of differentiation for these two related cutaneous lesions.

Psammomatous malignant melanoma arising in an intradermal naevus.

AIMS: A wide variety of differentiation patterns may be found in malignant melanoma. Schwannian features are unusual, and mostly present in the desmoplastic variant. We report the first description of psammoma bodies in malignant melanoma. METHODS AND RESULTS: A malignant melanoma arose in an intradermal naevus of the scalp in a 51-year-old woman, displaying focal neural-like features in the form of rosette-like pseudo-meissnerian alveolar nests, as well as numerous psammoma bodies grouped in a few areas. Tumour cell immunostaining for S100, HMB45, NKI-C3, and vimentin was detected. In addition, both malignant and benign melanocytic cells showed widespread MART-1 immunoreactivity. Differential diagnosis with psammomatous melanotic schwannoma, a feature of Carney's complex, is particularly emphasized, since dermal variants of this nerve sheath neoplasm have been described. In addition, its potential relationship with cutaneous malignant melanotic neurocristic tumour is discussed. CONCLUSIONS: This is, to our knowledge, the first reported case of cutaneous malignant melanoma with psammoma bodies.

Management of biliary duct confluence injuries produced by hepatic hydatidosis.

From 1978 to 1999 a total of 850 patients underwent surgical treatment for hydatid disease of the liver at our surgical department. Biliary duct confluence injuries produced by hepatic hydatidosis (HH) were founded in six patients (0.7%). Surgical intervention was undertaken to relieve the obstructive jaundice and clinical manifestations of cholangitis and to treat the hydatid cyst. A partially open cystopericystectomy technique was used in three patients with a double bilioenteric Roux-en-Y reconstruction. The remaining three patients (two with prehepatic portal hypertension and one with triple hepatic duct confluence) were subjected to a cystojejunostomy. There were no hospital deaths. Two cases of anastomotic leakage following a high bilioenteric anastomosis occurred but did not require surgical treatment. During the follow-up (5-19 years) one patient suffered local recurrence of the hydatid disease 7 years after cystojejunostomy. The site of intrahepatic biliary and vascular involvement, the presence of biliary duct anomalies, and the presence of portal hypertension are decisive factors when choosing the "ideal" procedure for reconstruction. Conservative surgical approaches (partial cystectomy and cystojejunostomy) are the treatments of choice. Radical surgery is often a serious matter.

Prevalence of infection with hepatitis C virus in Venezuela, as assessed with an immuno-assay based on synthetic peptides.

Information on infection with hepatitis C virus (HCV) in South America is scarce. The seroprevalences of antibodies to HCV among urban, rural and Amerindian populations from Venezuela, and the genotypes of the HCV isolates recovered, were therefore determined. A total of 2592 sera were tested with an immuno-assay which was developed in-house and based on synthetic peptides. Each reactive sample was then re-tested, using other enzyme immuno-assays and a reverse-transcription, nested PCR, and any sample confirmed positive (in any test) was considered HCV-positive. Genotypes were determined by analysis of RFLP. Overall, 39 (1.5%) of the samples were found HCV positive. The results of the immuno-assays indicated that the seroprevalence of HCV markers among the Amerindians investigated (23/1082, or 2.1%) was significantly higher than that among the other subjects (16/1510, or 1.1%; P = 0.02). No such difference was observed in the numbers of subjects confirmed positive by PCR, however (6/1082 v. 10/1510), and some of the anti-HCV reactivity observed among Amerindians may have been the result of cross-reactivity with parasitic infections. The relative low prevalence of active HCV infection (16/2582, or 0.6%) and the HCV genotypes observed (mainly genotype 1) are in agreement with the results of previous studies indicating that HCV is not autochthonous to South America. However, it is clear that the virus may now be found even in isolated Amerindian populations. The in-house, synthetic-peptide-based immuno-assay seems to be a valuable tool for epidemiological studies.

The role of multimodality therapy for resectable esophageal cancer.

BACKGROUND: There is an increasing interest in the role of combined therapy to achieve long-term survival for patients with resectable esophageal neoplasms. Surgery provides excellent palliation with relatively low morbidity and mortality rates, but cure remains elusive. MATERIAL AND METHODS: From January 1988 to January 1998, a total of 137 patients met eligibility criteria for a combined multimodal therapy, prospective, nonrandomized protocol of induction chemoradiation therapy followed by surgical resection, based on radiological and endoscopic assessment of the extension (all patients were initially considered to be at clinical stages I to III, locoregional). Consequently, patients with high grade Barrett's dysplasia or any squamous carcinoma in situ (stage 0) and those with distant metastatic disease (stage IV) were excluded. Among this group, 48 operable patients with biopsy-proven esophageal cancer finally entered and completed the protocol and are the sample of the present study. Multivariate logistic regression models were used to identify risk factors for death or recurrence. Actuarial survival was calculated since the beginning of the induction protocol by the Kaplan-Meier method, and comparisons between groups were made by the log-rank test. RESULTS: Mean age was 61.6 (range 45 to 71), and 72.9% were male. The majority of the tumors (70.8%) were located at the lower third/cardia and as many as 18.8% were adenocarcinoma. After a mean of 7.5 weeks (range 5 to 12) after the completion of the induction phase, 68.7% underwent a transthoracic esophagectomy and 31.3% a transhiatal esophagectomy. The in-hospital mortality rate was 10.4% (5 patients). A complete response (no evidence of tumor within the specimen: pT0) was achieved in 25% (12 patients). After a mean follow-up of 20.2 months, mean survival for the entire group was 18.2 months (95% confidence interval 14 to 22). At the end of the study, 25% (12) remained alive. Actuarial survival rates at 12, 23, and 37 months were 56.2%, 36.9%, and 21.9%, respectively. CONCLUSIONS: Esophageal resection after induction therapy seems to be related to a slightly higher mortality rate compared with historical series, and for this reason, neoadjuvant therapy must be considered still experimental. However, no statistical significant difference in survival is showed in those cases with complete pathological response (pT0). Factors influencing survival are recurrence and age. Surgery alone remains the standard therapy for esophageal cancer.

Restricted isotypic antibody reactivity to hepatitis C virus synthetic peptides in immunocompromised patients.

An enzyme immunoassay based on three synthetic peptides from the core, NS4, and NS5 regions of hepatitis C virus allowed the detection of antibodies in 100% of immunocompetent infected patients and in 91% of immunocompromised patients (hemodialysis and hemophiliac patients). Immune impairment seemed to restrict the spectrum of antibody isotypes reacting to the core peptide.

Safety and efficacy of dynamic muscle plasty for anal incontinence: lessons from a prospective, multicenter trial.

BACKGROUND & AIMS: Dynamic muscle plasty has been advocated as therapy for refractory fecal incontinence and for anorectal reconstruction to avoid colostomy after abdominoperineal resection. This study evaluates the results of a multicenter experience with dynamic muscle plasty in the treatment of fecal incontinence and total anal reconstruction. METHODS: One hundred thirty-nine patients were enrolled at 12 centers between June 1992 and November 1994 and followed up through June 1996. Intramuscular leads and neurostimulators were implanted to stimulate transposed gracilis or gluteus muscle. Success was defined as 70% reduction in solid stool incontinence for patients with baseline incontinence and zero incontinence to solid stool for patients with baseline stomas and for patients undergoing total anal reconstruction. RESULTS: Overall, 85 of 128 graciloplasty patients (66%) achieved and maintained a successful outcome over the follow-up period. By etiology, these proportions were 71%, 50%, and 66% for patients with acquired fecal incontinence, congenital incontinence, and total anal reconstruction, respectively. One third of graciloplasty patients experienced a major wound complication, with therapy failing in 41%. Experienced centers had better outcomes and lower complication rates than inexperienced centers. Of the 11 gluteoplasty patients, 5 (45%) achieved and maintained a successful outcome. CONCLUSIONS: Dynamic graciloplasty may be an effective procedure for patients with refractory, end-stage fecal incontinence as well as for patients who require anorectal excision for low-lying malignancy. However, the procedure has significant morbidity that can lead to functional failure. Outcome after dynamic graciloplasty appears to correlate with surgical experience. In contrast to graciloplasty, the use of dynamic gluteoplasty should be limited to investigational purposes.