RESUMEN
Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdominal infections have a common pathogenesis but some microbiological differences, particularly with respect to the type of bacteria recovered and the level of antimicrobial susceptibility. This report describes a prospective observational study of 93 consecutive patients with secondary peritonitis during an 11-month period. Community-acquired peritonitis accounted for 44 cases and nosocomial peritonitis for 49 cases (post-operative in 35 cases). Fifteen multidrug-resistant (MDR) bacteria were recovered from 14 patients. In univariate analysis, the presence of MDR bacteria was associated significantly with pre-operative and total hospital lengths of stay, previous use of antimicrobial therapy, and post-operative antimicrobial therapy duration and modifications. A 5-day cut-off in length of hospital stay had the best specificity (58%) and sensitivity (93%) for predicting whether MDR bacteria were present. In multivariate analysis, only a composite variable associating pre-operative hospital length of stay and previous use of antimicrobial therapy was a significant independent risk-factor for infection with MDR bacteria. In conclusion, knowledge of these two factors may provide a more rational basis for selecting initial antimicrobial therapy for patients with secondary peritonitis.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Peritonitis/tratamiento farmacológico , Peritonitis/microbiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Humanos , Incidencia , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The purpose of this study was to evaluate the outcomes and the five-year survival of 179 consecutive patients with rectal carcinoma operated with a laparoscopic procedure between April 1992 and April 2003. METHODS: Patients with obstructing, bulky cancers were excluded from this study. Tumor stage was defined according to the TNM classification. Preoperative radiation therapy was offered to T(3) N(0) or N(+) patients (45 Gy). The laparoscopic-assisted technique included total mesorectal excision (TME), primary high vascular ligation, centrifugal dissection of the mesentery, and "no touch" technique. All the N+ patients received adjuvant chemotherapy. The outcomes were defined as five-years recurrence (local recurrence and distant metastasis) and the diseases-free survival. The survival rates were calculated with the Kaplan-Meier test. RESULTS: There were 108 males and 71 females, median age was 67 (range 39-88). There were 61 upper rectum localizations (34%), 68 middle rectum (38%) and 50 low rectum (28%). Twenty-nine patients required open conversion (16%). Surgical operative morbidity was 24% and medical morbidity was 4%. There were 60 stage I (40%), 25 stage II (16%), 49 stage III (32%), and 16 stage IV (10%). Ninety patients (71%) are alive and disease free, ten (5%) are alive with disease recurrence, and 37 patients (20%) are deceased. Only one case of trocar site implantation occurred after curative resection during an average follow up of 76 months. Five-year observed survival rate were 85% for stage I, 70% for stage II, and 63% for stage III. CONCLUSION: In our experience laparoscopic rectal resection could be done safely. The oncologic outcome was similar to that of open surgery. Further randomized trials will be necessary to confirm the value of this technique.
Asunto(s)
Laparoscopía/métodos , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The laparoscopic approach promises to become the gold standard for the transabdominal management of full-thickness rectal prolapse. The aim of this study was to review our experience and to highlight the functional results achieved with this new technique. METHODS: Forty-eight patients with full-thickness external prolapse underwent laparoscopic repair between February 1997 and February 2003. All patients underwent preoperative evaluation of their rectal function. Patients with isolated rectal ulcer without prolapse or with internal prolapse and patients deemed by the anesthesiologist to be unfit for general anesthesia were excluded from the study. The laparoscopic technique was either a mesh rectopexy without resection (n = 35) or a suture rectopexy with sigmoid resection (n = 13). Patients with intractable constipation preceding the development of the rectal prolapse were advised to have a resection-rectopexy. In the postoperative follow-up, attention was paid to mortality, morbidity, recurrent prolapse, incontinence, and constipation. Follow-up was done by clinical review and postal questionnaire. RESULTS: There were no deaths and no septic or anastomotic complications. The postoperative morbidity rate was 5%. Oral intake was started on postoperative day 1. Discharge from the hospital was on postoperative day 4 in patients without sigmoid resection and on postoperative day 7 in patients with sigmoid resection. Two patients (4%) developed recurrent total prolapse during a median follow-up period of 36 +/- 15 months (range, 7-77). The functional results were good or excellent in 72% of the cases, without digitations or dyschesia. Continence was improved in 31% of the patients and remains unchanged in 64% of them. In 11 patients (23%), constipation was worsened by the procedure. CONCLUSION: Laparoscopic rectopexy with or without resection is both safe and effective. Advantages include low-morbidity, improved cosmesis, the rapid return of intestinal function, early discharge from hospital, and a low recurrence rate. The fecal continence score is improved; however, constipation is frequently worsened.
Asunto(s)
Laparoscopía/métodos , Prolapso Rectal/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Colon Sigmoide/cirugía , Estreñimiento/etiología , Incontinencia Fecal/etiología , Incontinencia Fecal/cirugía , Femenino , Estudios de Seguimiento , Tránsito Gastrointestinal , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Peritoneo , Complicaciones Posoperatorias/epidemiología , Prolapso Rectal/complicaciones , Recurrencia , Estudios Retrospectivos , Mallas Quirúrgicas , Grapado Quirúrgico , Técnicas de Sutura , Resultado del Tratamiento , ÚteroRESUMEN
BACKGROUND: Recurrence is common after surgery for hepatocellular carcinoma (HCC). METHODS: The efficacy of, and tolerance to, preoperative intra-arterial injection of (131)I-labelled lipiodol was examined in 34 patients with HCC, including 29 with cirrhosis. Twenty-five patients had a single hepatic tumour and the mean(s.d.) tumour size was 5.2(3.7) (range 2-15) cm. The patients received between one and three injections of (131)I-labelled lipiodol (60 mCi per injection) before surgery. Operations included 14 liver transplants, 13 minor hepatectomies, six major hepatectomies and one exploratory laparotomy. RESULTS: There was one complication after lipiodol injection due to acute ischaemia of the small bowel. Three of 34 patients died within 28 days, two after transplantation and one after resection. An objective tumour response (decrease in tumour size) was observed in 19 of 34 patients, and a complete histological response in eight of 34. There was an objective tumour response or major histological necrosis of lesions in 25 of 34 patients. The 5-year survival rate was 48.4(8.0) per cent, 69.0 per cent after transplantation and 36.0 per cent in patients who underwent resection. CONCLUSION: This preoperative method appeared to be well tolerated, and provided promising results in terms of macroscopic and microscopic tumour responses.
Asunto(s)
Carcinoma Hepatocelular/radioterapia , Medios de Contraste , Radioisótopos de Yodo/administración & dosificación , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/radioterapia , Carcinoma Hepatocelular/cirugía , Femenino , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Inyecciones Intraarteriales , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Cuidados Preoperatorios/métodos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.
Asunto(s)
Quimiocinas CC/metabolismo , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Quimiocina CCL17 , Quimiocina CCL22 , Quimiocinas CC/análisis , Niño , Colitis Ulcerosa/patología , Enfermedad de Crohn/patología , Humanos , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Leucocitos Mononucleares/metabolismo , Persona de Mediana Edad , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células TH1/metabolismo , Células Th2/metabolismoRESUMEN
BACKGROUND AND METHODS: The aim of this study was to evaluate the efficacy of hypothermic machine perfusion (HMP) to preserve rat livers according to the route of perfusion, i.e., via portal vein, hepatic veins (retrograde), or hepatic artery. Livers were preserved for 24 or 48 hr by simple cold storage (SCS) or by HMP. Preservation solution was supplemented with (HMP) or without (SCS) hydroxyethyl starch. After preservation, grafts were reperfused for 2 hr with an oxygenated Krebs-Henseleit bicarbonate buffer. RESULTS: After 24 hr of preservation, total glutathione concentrations in HMP livers were similar (1287+/-37, 1418+/-118, and 1471+/-62 nmol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in the SCS (833+/-118 nmol/g, P<0.05) group. These higher total glutathione values were due to higher reduced glutathione concentrations. ATP concentrations in the liver tissue were similar in HMP groups (0.75+/-0.4, 0.64+/-0.1, and 0.77+/-0.1 micromol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in SCS (0.32+/-0.06 micromol/g, P<0.05). After 2 hr of normothermic reperfusion, bile production in the HMP portal and HMP retrograde groups were similar (391+/-29 ml and 372+/-25 ml) and higher than in the HMP artery or SCS groups (275+/-25 ml and 277+/-32 ml, respectively; P<0.05). Aspartate transaminase, alanine transaminase, lactate dehydrogenase, and purine nucleoside phosphorylase release into the perfusate of HMP portal and HMP retrograde perfused livers was similar and significantly lower compared to the HMP artery and SCS groups. At the end of reperfusion, no statistical differences were found for glutathione concentration and energetic reserves in the livers of each group. After 48 hr of preservation, livers from the HMP portal and HMP retrograde groups did significantly better than livers from the HMP artery or SCS groups. CONCLUSIONS: This study confirms the superiority of HMP over SCS to preserve the liver graft. It shows that retrograde perfusion is similar to PV perfusion and that perfusion by HA is less beneficial.
Asunto(s)
Hipotermia Inducida/métodos , Hígado/fisiopatología , Soluciones Preservantes de Órganos/administración & dosificación , Perfusión/métodos , Animales , Criopreservación , Arteria Hepática , Venas Hepáticas , Técnicas In Vitro , Inyecciones Intraarteriales , Inyecciones Intravenosas , Masculino , Vena Porta , Ratas , Ratas Wistar , Valores de Referencia , Reperfusión , Factores de TiempoRESUMEN
Over a 12-month period, we diagnosed poorly differentiated infiltrative independent-cell gastric adenocarcinoma in two brothers and one sister aged 41 to 47 years. Their father had died from antral cancer at the age of 34 years. These cancers had two characteristic clinical features: rapid course and distant malignant dissemination. In all three patients, polymerase chain reaction-sequencing of the E-cadherin (CDH1) gene of white blood cells identified a heterozygous nonsense mutation of exon 3, producing a stop codon at position 95 (Q95X), resulting in a truncated protein. The alteration of this protein, which plays a crucial role in epithelial cell adhesion, probably explains the clinical expression in this type of familial diffuse gastric cancer.
Asunto(s)
Cadherinas/genética , Linitis Plástica/diagnóstico , Linitis Plástica/genética , Mutación , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adulto , Endosonografía , Resultado Fatal , Femenino , Estudios de Seguimiento , Gastrectomía , Mucosa Gástrica/patología , Marcadores Genéticos/genética , Humanos , Linitis Plástica/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Linaje , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
Matrix metalloproteinase-2 (MMP2) is a key enzyme in the process of extracellular matrix remodeling involved in tumor invasion and metastasis. The activation of MMP2 involves interplay with the membrane type-matrix metalloproteinase-1 (MT1-MMP) and the tissue inhibitor of metalloproteinase-2 (TIMP2). In vitro, activated hepatic stellate cells are a main source of MMP2 and collagen I induces MMP2 activation. The steady-state mRNA levels of MMP2, MT1-MMP, TIMP2, collagen I, collagen IV, and laminin gamma1 were compared with MMP2 activity in 55 hepatocellular carcinomas, 47 matching nontumor biopsies and 19 histologically normal livers. In hepatocellular carcinomas, increased collagen I mRNA levels were strongly associated with those of MMP2 (Spearman R =.74, P <.001), MT1-MMP (R =.65, P <.001) and TIMP2 (R = 0.61, P <.001). MMP2 activity was correlated with the mRNA expression of collagen I (R =.45 P <.01), collagen IV (R =.40, P <.01) and laminin gamma1 (R =.33, P <.05). Unlike collagen IV and laminin gamma1 mRNAs, MMP2, MT1-MMP, TIMP2, collagen I mRNA levels were increased in nonencapsulated compared with encapsulated tumors (P <.05). In addition, MMP2 activity was fourfold higher (P <.01) in tumors arising in cirrhotic livers than in those arising in noncirrhotic livers. Moreover, tumor recurrence was associated with 4.6- and 2.8-fold (P <.05) higher collagen I and MMP2 mRNA levels, respectively, in hepatocellular carcinomas arising in cirrhotic livers. Thus, a high extracellular matrix remodeling favors tumor progression in hepatocellular carcinomas.
Asunto(s)
Carcinoma Hepatocelular/patología , Matriz Extracelular/metabolismo , Neoplasias Hepáticas/patología , Anciano , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/enzimología , Colágeno/genética , Colágeno/farmacología , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , Laminina/genética , Neoplasias Hepáticas/química , Neoplasias Hepáticas/enzimología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasas de la Matriz Asociadas a la Membrana , Metaloendopeptidasas/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia , ARN Mensajero/análisis , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
Endostatin is an endogenous inhibitor of angiogenesis and tumor growth in mice, which may be generated by proteolytic cleavage of collagen XVIII. In normal tissues, 2 variants of the endostatin precursor, namely the SHORT and LONG forms, regulate tissue specificity. We analyzed 53 human liver biopsies (18 hepatocellular carcinomas, 16 metastases of colorectal cancer, 3 cholangiocarcinomas, and 16 controls) by RNA dot blots, double-labeling immunohistochemistry, and in situ hybridization, using common and variant-specific probes. Tumor hepatocytes expressed the LONG form, whereas cholangiocarcinoma cells expressed the SHORT form, which was deposited in tumor basement membranes. Metastatic colorectal carcinoma cells did not express collagen XVIII. In the stromal compartment of primary and metastatic cancers, myofibroblasts and vascular endothelial cells expressed the SHORT form. Both basement membrane components, collagen IV and the SHORT collagen XVIII form, were codistributed and their mRNA levels strongly correlated (R =.75, P <.001). In addition, freshly isolated human hepatocytes expressed the LONG form and culture-activated stellate cells the SHORT form. Moreover, the full-length LONG form is a plasma protein. Thus, the LONG form is a hepatocyte-specific variant, and the SHORT form is a major component of the tumor extracellular matrix in primary and metastatic liver cancers. In the clinical context, the global expression of the endogenous endostatin precursor, collagen XVIII, in liver cancer results from the combined expression profiles of tumor cells, stromal cells, and nontumor hepatocytes at the advancing edge of the tumor, particular to each type of cancer.
Asunto(s)
Colágeno/biosíntesis , Hepatocitos/metabolismo , Neoplasias Hepáticas/metabolismo , Fragmentos de Péptidos/biosíntesis , Membrana Basal/fisiología , Neoplasias de los Conductos Biliares/metabolismo , Proteínas Sanguíneas/biosíntesis , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/fisiopatología , Células Cultivadas , Colangiocarcinoma/metabolismo , Colágeno/química , Colágeno Tipo XVIII , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Endostatinas , Fibroblastos/metabolismo , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/secundario , Músculo Liso/metabolismo , Músculo Liso/patología , Fragmentos de Péptidos/química , Células del Estroma/metabolismoRESUMEN
Endostatin inhibits angiogenesis and tumor growth in mice. The role of its endogenous precursor collagen XVIII in human cancer is unknown. In normal tissues, two variants of collagen XVIII, namely, the short and long forms regulate tissue specificity, the long form being almost exclusively expressed by hepatocytes in the liver. We analyzed RNA arrays from 57 hepatocellular carcinomas (HCCs) with common and variant-specific probes and investigated the relationships between collagen XVIII expression and angiogenesis by measuring the CD34-positive microvessel density. Low collagen XVIII expression by tumor hepatocytes was associated with large tumor size (r, -0.63; P < 0.001) and replacement of trabeculae with pseudoglandular-solid architecture (chi2, 28; P < 0.001), which indicate tumor progression. Tumors expressing the highest collagen XVIII levels were smaller and had lower microvessel density (P = 0.01) than those expressing moderate levels; and HCCs with the lowest collagen XVIII levels approached a plateau of microvessel density, which indicated that a decrease in collagen XVIII expression is associated with angiogenesis in primary liver cancer. HCCs recurring within 2 years of resection showed 2.2-fold lower collagen XVIII mRNA than nonrecurring ones (P = 0.02). The findings relied on the hepatocyte-specific long form. Thus, the endogenous expression of the endostatin precursor decreases along with tumor progression in HCCs.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Colágeno/biosíntesis , Neoplasias Hepáticas/metabolismo , Fragmentos de Péptidos/biosíntesis , Empalme Alternativo , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/patología , Colágeno Tipo XVIII , Progresión de la Enfermedad , Endostatinas , Femenino , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Masculino , Neovascularización Patológica/metabolismo , ARN Mensajero/metabolismoRESUMEN
Organic anion secretion by human hepatocytes was characterized using primary liver parenchymal cell cultures and the anionic fluorescent dye carboxy-2',7'-dichlorofluorescein (CF). Probenecid, a well-known common blocker of the membrane transport process for anions, was shown to increase CF accumulation in primary human hepatocytes by inhibiting cellular CF efflux in a dose-dependent manner, thereby establishing the presence of an efflux system for organic anions in cultured hepatocytes. Outwardly directed transport of CF from hepatocytes was found to be temperature-dependent; it was not altered by changes in the ionic composition of the incubation medium used in efflux experiments. In addition to probenecid, various structurally and functionally unrelated xenobiotics such as glibenclamide, rifampicin, vinblastine, MK-571, indomethacin, and cyclosporin A were shown to inhibit secretion of CF by primary human hepatocytes, thus suggesting that organic anion excretion by human liver may be impaired by various drugs. Northern blot and Western blot analyses of the expression of multidrug resistance proteins (MRP), such as MRP1 and MRP2, which are known to mediate cellular outwardly directed transport of organic anions indicated that MRP2 was present at substantial levels in cultured human hepatocytes as well as in their in vivo counterparts, whereas MRP1 expression was only barely detectable. These results therefore suggest that MRP2, unlike MRP1, may contribute to the organic anion efflux system displayed by primary human hepatocytes and inhibited by a wide range of xenobiotics.
Asunto(s)
Fluoresceínas/metabolismo , Hepatocitos/efectos de los fármacos , Xenobióticos/farmacología , Proteínas de Transporte de Anión , Aniones/metabolismo , Transporte Biológico/efectos de los fármacos , Proteínas Portadoras/metabolismo , Células Cultivadas , Hepatocitos/metabolismo , HumanosRESUMEN
BACKGROUND: Both livers and hepatocytes from pigs have been proposed for the treatment of end-stage liver diseases, as an alternative to allogeneic liver transplants. However, little is known of the capability of porcine hepatocytes to fulfill the biotransformation pathways of toxic compounds, including those released from livers in acute failure. We have studied the activity and expression of detoxifying enzymes in porcine livers and in cultured hepatocytes and their induction by phenobarbital. METHODS: Cytochromes P450 (CYP) 1A, 2B, and 3A and GST-like activities were tested with the following specific substrates: 7-ethoxyresorufin, 7-pentoxyresorufin, nifedipine, testosterone, 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrinic acid. CYP 1A1/2-, 2B1/2-, 2E1- and 3A4-related and GSTalpha proteins were analyzed by Western blotting and CYP 1A1/2, 2B1/2, 2C6, 2E1, and 3A4, aldehyde dehydrogenase, epoxide hydrolase, and GSTalpha-like RNA by Northern blotting. RESULTS: Enzymatic activities reflecting the expression of CYP 1A-, CYP 2B-, CYP 2E1-, and CYP 3A-like genes, that is, ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase, nifedipine oxidase and testosterone 6beta-hydroxylase, and chlorzoxazone 6-hydroxylase, were identified in pig livers. CYP 1A and CYP 2E1, GSTalpha-like proteins, CYP 1A, 2C, and 2E, epoxide hydrolase, aldehyde dehydrogenase, and GST like RNA were expressed in vivo and in vitro. CYP 2B and CYP 3A RNA and proteins, and their associated activities were induced by phenobarbital. CONCLUSIONS: Porcine hepatocytes express the most important biotransformation enzymes and their corresponding activities and RNA. Thus, livers and hepatocytes from pigs can detoxify a large spectrum of exogenous and endogenous compounds, which makes them a convenient substitute for allogeneic transplants for patients with liver failure.
Asunto(s)
Trasplante de Células , Sistema Enzimático del Citocromo P-450/metabolismo , Glutatión Transferasa/metabolismo , Trasplante de Hígado , Hígado/citología , Hígado/enzimología , Trasplante Heterólogo , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Animales , Células Cultivadas , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Citosol/enzimología , Epóxido Hidrolasas/genética , Epóxido Hidrolasas/metabolismo , Femenino , Glutatión Transferasa/genética , Isoenzimas/metabolismo , Microsomas Hepáticos/enzimología , PorcinosRESUMEN
OBJECTIVE: To review and update the authors' experience with resectional surgery for proximal bile duct carcinoma (Klatskin tumor) and assess the role of liver resection over the past 25 years. BACKGROUND: Until recently, resection of proximal bile duct carcinoma was uncommon, with most patients undergoing palliative procedures. The authors adopted a radical surgical approach aimed at definitive cure in 1974. Recent reports suggest that resection improves outcome. METHODS: The records of 40 of 94 patients (23 men, 17 women, age range 34-81 years) diagnosed with proximal bile duct carcinoma who underwent resection between 1968 and 1993 were reviewed. According to the Bismuth classification, there were five type I, four type II, 25 type III, and six type IV lesions; 11 patients underwent tumor resection alone, and 25 patients had combined tumor and liver resection (seven of these also underwent an associated regional vascular resection). In 3 patients, venous allografts were harvested from cadaveric donors and used to reconstruct the portal vein. Four patients underwent liver transplantation; in two, organ cluster-type resections including the liver with porta hepatitis and pancreas were performed. RESULTS: The resectability rate in the more recent period of the study was 49.4%. Most type I, three (of four) type II, T in situ, T1a, T1b, and all stage 0 tumors were resected without hepatectomy. In the other subgroups of tumors, the main surgical procedure was hepatectomy. Thirty-day mortality was 12.5%. After tumor resection alone, survival at 1, 3, and 5 years was 81.8%, 45.5%, and 27.3%, respectively. After tumor resection and hepatectomy without vascular resection, 1-, 3-, and 5-year survival was 66.7%, 16.7%, and 6%, respectively. With vascular resection, survival rates were similar: 64%, 20%, and 4%, respectively. CONCLUSION: The type of surgery required to achieve cure is closely related to tumor location, TNM classification, and staging. Increasing resectability through the use of hepatectomy improves survival and offers a chance of cure in patients with more advanced disease.
Asunto(s)
Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Conducto Hepático Común , Tumor de Klatskin/mortalidad , Tumor de Klatskin/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/patología , Femenino , Humanos , Tumor de Klatskin/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Procedimientos Quirúrgicos Operativos/métodos , Tasa de Supervivencia , Factores de TiempoRESUMEN
Portal vein resection during pancreaticoduodenectomy has recently experienced renewed interest. We describe our results with this procedure over a 20-year period. Among 88 consecutive pancreatectomies for cancer of head of the pancreas, 14 included en bloc removal of the portal vein. There was no hospital mortality. Only 21% were found to have histologically confirmed cancer invasion, and the remainder had inflammatory adherence. Two-year survival was 15% compared to 34% for patients who did not have portal vein resection. There were no 5-year survivors. We discuss our results in light of other recent reports.
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Adenocarcinoma/cirugía , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Vena Porta/cirugía , Adenocarcinoma/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Hemangiopericytoma is an uncommon vascular tumor which usually develops in soft tissues. It has been exceptionally described in the liver and only one case associated with hypoglycemia has been reported in this organ. A giant hemangiopericytoma which was revealed by life-threatening hypoglycemia is described. Imaging and pathological features are presented. The patient, a 73 year-old woman, was treated by hepatectomy. She is perfectly well after a 3-year follow-up, without any evidence of recurrence.
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Hemangiopericitoma/diagnóstico , Hipoglucemia/etiología , Neoplasias Hepáticas/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Hemangiopericitoma/patología , Hemangiopericitoma/cirugía , Hepatectomía , Humanos , Hipoglucemia/patología , Hipoglucemia/cirugía , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological analysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specimens were utilized: 39 specimens with esophageal dysplasia and adenocarcinoma and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dyplasia and carcinoma) examined from 44 patients. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immunohistochemistry. Low-grade dysplasia was present in 14 sections, high-grade dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression occurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out of 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sections with carcinoma (p<0.001). p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with high-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dysplasia but immunoreactivity was not seen in any section with high-grade dysplasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events during neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcinoma, the balance of proliferation/apoptosis plays an important role.
Asunto(s)
Esófago de Barrett/metabolismo , Antígeno Ki-67/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteína p53 Supresora de Tumor/análisis , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To assess the results of a refined approach to repair of postcholecystectomy bile duct strictures. DESIGN: An 11-year retrospective review of patients who had surgical repair of bile duct strictures developing late after cholecystectomy. SETTING: A major university teaching hospital in France. PATIENTS AND INTERVENTIONS: During an 11-year period from 1987 to 1997, 22 patients (mean [+/-SD] age, 55+/-15 years) were operated on for bile duct strictures after cholecystectomy (11 after laparoscopic surgery and 11 after open surgery). Thirteen (59%) of the 22 patients had previous repair. Most patients had episodic cholangitis (14 patients [64%]) and biochemical evidence of cholestasis (20 patients [91%]). There were 5 Bismuth type 1 strictures; 4, type 2; 7, type 3; 5, type 4; and 1, type 5. The average (+/-SD) time from initial surgery to repair was 6.3+/-9.6 years. Intraoperative cholangiography was used to plan the repair in 18 patients (82%). Fifteen patients (68%) were repaired with high Hepp-Couinaud hepaticojejunostomies. The last 4 patients had the hilum exteriorized by the posterior approach to improve access. RESULTS: There was 1 intraoperative complication (bleeding) and 4 postoperative complications (biloma, fistula, and 2 cholangitis). There were no deaths; mean (+/-SD) length of stay was 12.8+/-5.8 days; and mean (+/-SD) follow-up was 4.8+/-3.3 years (range, 1-10.7 years). Three patients were reoperated on, 1 with an obstructed Roux-en-Y limb and the 2 others for incisional hernias. Eighteen patients remain well, 3 had sporadic recurrent cholangitis after surgery that resolved spontaneously, and 1 patient remains unwell requiring antibiotics to control cholangitis. CONCLUSIONS: Hepp-Couinaud hepaticojejunostomy without stenting remains a reliable repair of postcholecystectomy strictures. Intraoperative cholangiography and exteriorizing the hilum by the posterior approach are useful adjuncts to this technique.
Asunto(s)
Colecistectomía/efectos adversos , Colestasis/cirugía , Procedimientos Quirúrgicos del Sistema Biliar/métodos , Colestasis/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Matrix metalloproteinase-2 (MMP2) activation is associated with basement membrane remodeling that occurs in injured tissues and during tumor invasion. The newly described membrane-type MMPs (MT-MMPs) form a family of potential MMP2 activators. We investigated the localization and steady-state levels of MT1-MMP and MT2-MMP mRNA, compared with those of MMP2 and tissue inhibitor of MMP-2 in 22 hepatocellular carcinomas, 12 liver metastases from colonic adenocarcinomas, 13 nontumoral samples from livers with metastases, 10 benign tumors, and 6 normal livers. MMP2 activation was analyzed by zymography in the same series. The expression of MT1-MMP mRNA and the activation of MMP-2 were increased in hepatocellular carcinomas, metastases, and cholestatic nontumoral samples. MT2-MMP mRNA was rather stable in the different groups. MT1-MMP mRNA levels, but not MT2-MMP mRNA, correlated with MMP-2 and tissue inhibitor of MMP-2 mRNA levels and with MMP2 activation. In situ hybridization showed that MT1-MMP mRNA was expressed in stromal cells, and MT2-MMP mRNA was principally located in both hepatocytes and biliary epithelial cells. Consistently, freshly isolated hepatocytes expressed only MT2-MMP mRNA, and culture-activated hepatic stellate cells showed high levels of MT1-MMP mRNA. These results indicate that in injured livers, MMP2 activation is related to a coordinated high expression of MMP2, tissue inhibitor of MMP-2, and MT1-MMP. Furthermore, the finding of a preferential expression of MT2-MMP in hepatocytes, together with our previous demonstration that the activation of stellate cell-derived MMP2 in co-culture requires interactions with hepatocytes (Am J Pathol 1997, 150:51-58), suggests that parenchymal cells might play a pivotal role in the MMP2 activation process.