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3.
J Am Coll Surg ; 193(1): 73-80, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11442257

RESUMO

BACKGROUND: Education is a major function of academic medical centers. At these teaching institutions residents provide a substantial amount of care on medical and surgical services. The attitudes of patients about the training of surgical residents and the impact of residents on patients' perceptions of care in a surgical setting are unknown. STUDY DESIGN: Patients admitted to the gastrointestinal surgery service completed a 30-item survey designed for this study. Patients included in the study underwent operations and had a postoperative inpatient hospital stay. We analyzed patients' answers to determine frequency and correlations among answers. RESULTS: Two hundred patients participated in the study during a 7-month period between July 1999 and January 2000. A majority of patients were comfortable having residents involved in their care (86%) and felt it was important to help educate future surgeons (91%). Most did not feel inconvenienced by being at a teaching hospital (71%) and felt they received extra attention there (74%). Patients were more willing to participate in resident education if they expected to have several physicians involved in their care, felt that they received extra attention, or if the teaching atmosphere did not inconvenience them. Despite the stated willingness of patients to help with surgical resident education, 32% answered that they would not want residents doing any of their operation. CONCLUSIONS: Surgical resident education is well received and considered important by patients. Patient orientation to the resident education process is vital to patients' perceptions of care and may render patients more willing to participate in educational activities.


Assuntos
Cirurgia Geral/educação , Internato e Residência , Pacientes/psicologia , Relações Médico-Paciente , Centros Médicos Acadêmicos , Atitude Frente a Saúde , Coleta de Dados , Feminino , Gastroenteropatias/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Centro Cirúrgico Hospitalar
4.
Am Surg ; 67(2): 182-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11243547

RESUMO

Hereditary pancreatitis is an uncommon cause of chronic pancreatitis in Western society. It should be suspected when chronic pancreatitis presents in young adults. The diagnosis is made when chronic pancreatitis is present in several members of the same family who are determined not to have other risk factors for chronic pancreatitis. Molecular research focusing on mutations in the trypsinogen gene has uncovered the genetic defects associated with hereditary pancreatitis, and this knowledge has suggested the possible pathophysiologic mechanism of this disease. Because patients with hereditary pancreatitis develop their disease early in life they are very likely to require treatment for complications. As in patients with chronic pancreatitis of other etiologies those with hereditary pancreatitis should be treated medically for acute exacerbations. When complications occur or when the disease causes intractable pain surgery is recommended. Surgical therapy is tailored to the patient's pancreatic anatomy based on endoscopic retrograde cholangiopancreatography or CT scan. The two patients described in this report underwent successful longitudinal pancreaticojejunostomy (Puestow procedure) with good results. Finally it has been shown that patients with hereditary pancreatitis are at increased risk for developing pancreatic adenocarcinoma. Although not widely used pancreatic cancer screening programs have been suggested for surveillance of these patients.


Assuntos
Pancreatite/genética , Dor Abdominal/etiologia , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Mutação , Pancreaticojejunostomia , Pancreatite/cirurgia , Fatores de Risco , Tripsinogênio/genética
5.
Am Surg ; 64(8): 711-6; discussion 716-7, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9697898

RESUMO

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.


Assuntos
Gastrectomia , Gastroparesia/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Anastomose em-Y de Roux , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Gastroparesia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reoperação , Estudos Retrospectivos
6.
Cancer Res ; 58(8): 1688-94, 1998 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-9563484

RESUMO

The purpose of this study was to determine the presence and extent of pulmonary elimination for 5-fluorouracil (FUra). A secondary aim was to characterize the relative importance of the liver, gastrointestinal tract, splanchnic region, and lungs toward the overall elimination of FUra. A total of 10 mixed-breed male and female dogs were used in these acute studies in which FUra was administered through a cephalic vein. Six dogs were studied at sequentially escalated dose rates of 0.125, 0.250, 0.500, 0.750, and 1.00 micromol/min/kg (8-fold range); four dogs were studied at sequentially escalated dose rates of 0.0625, 0.250, 0.750, 1.50, and 2.00 micromol/min/kg (32-fold range). Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (i.e., portal vein, carotid artery, hepatic vein, and pulmonary artery), perfusion rates were measured (hepatic artery, portal vein, and cardiac output), and pharmacokinetic parameters were directly assessed. Pulmonary elimination of FUra was conclusively demonstrated. Although only 17% of the drug was extracted by the lungs at the lowest dose rate, pulmonary clearance (16.0 ml/min/kg) was on the order of splanchnic clearance (13.5 ml/min/kg), or larger. As the dose rate increased, pulmonary clearance was more easily saturated than splanchnic clearance. Thus, it appears that at increasing dose rates, the splanchnic region becomes a more significant pathway, whereas the lungs have a reduced role in the overall elimination of FUra.


Assuntos
Sistema Digestório/metabolismo , Fluoruracila/farmacocinética , Fígado/metabolismo , Pulmão/metabolismo , Animais , Cães , Relação Dose-Resposta a Droga , Feminino , Hemodinâmica/efeitos dos fármacos , Masculino , Pâncreas/metabolismo , Baço/metabolismo
7.
J Comput Assist Tomogr ; 22(2): 335-9, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9530406

RESUMO

PURPOSE: The aim of this study was to evaluate the utility of dual-phase imaging in the assessment of nonfunctioning islet cell tumors (NFITs). METHOD: Six patients with histologically and biochemically proven NFIT were evaluated by arterial and portal venous dual-phase helical CT. Scan delay was 20 s for the arterial phase and 70 s for the portal phase. Each phase was assessed by consensus reading and specifically evaluated for tumor conspicuity, hepatic metastases, vascular encasement by tumor, and presence of lymphadenopathy. RESULTS: Overall, tumor conspicuity was greater in the arterial phase (5/6) than in the portal venous phase (1/6) with a mean tumor/normal pancreas attenuation difference of 31.8 HU in the arterial phase compared with 19.2 HU in the portal venous phase. The arterial phase detected a total of 17 liver metastases compared with 9 seen in the portal phase. Lymph node enlargement was noted in three patients, which, although visible in both phases, was more easily discernible in the arterial phase. Venous encasement by tumor was better evaluated on the delayed portal venous phase than the arterial phase. CONCLUSION: Dual-phase helical CT scanning leads to improvement in the detection and staging of NFITs.


Assuntos
Carcinoma de Células das Ilhotas Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Biópsia , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Meios de Contraste , Feminino , Humanos , Iohexol , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Veia Porta/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/instrumentação
8.
J Comput Assist Tomogr ; 22(1): 59-63, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9448762

RESUMO

PURPOSE: The aim of this study was to evaluate the utility of dual-phase imaging in the assessment of nonfunctioning islet cell tumors (NFITs). METHOD: Six patients with histologically and biochemically proven NFIT were evaluated by arterial and portal venous dual-phase helical CT. Scan delay was 20 s for the arterial phase and 70 s for the portal phase. Each phase was assessed by consensus reading and specifically evaluated for tumor conspicuity, hepatic metastases, vascular encasement by tumor, and presence of lymphadenopathy. RESULTS: Overall, tumor conspicuity was greater in the arterial phase (5/6) than in the portal venous phase (1/6) with a mean tumor/normal pancreas attenuation difference of 31.8 HU in the arterial phase compared with 19.2 HU in the portal venous phase. The arterial phase detected a total of 17 liver metastases compared with 9 seen in the portal phase. Lymph node enlargement was noted in three patients, which, although visible in both phases, was more easily discernible in the arterial phase. Venous encasement by tumor was better evaluated on the delayed portal venous phase than the arterial phase. CONCLUSION: Dual-phase helical CT scanning leads to improvement in the detection and staging of NFITs.


Assuntos
Carcinoma de Células das Ilhotas Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biópsia , Carcinoma de Células das Ilhotas Pancreáticas/patologia , Carcinoma de Células das Ilhotas Pancreáticas/secundário , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Doenças Linfáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Estudos Retrospectivos
9.
Gastroenterol Clin North Am ; 26(1): 103-28, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9119436

RESUMO

Carcinoma of the colon and rectum currently ranks as the second leading cause of death from cancer in the United States. Surgery remains the cornerstone of treatment for colorectal cancer but has inherent limitations imposed by the biology and stage of the tumor and its location. Ultimately, 50% of patients who undergo curative resection develop local, regional, or widespread recurrence. These statistics have remained relatively constant over several decades despite improved methods of early diagnosis and surgical treatment but may change as new multimodality treatment regimens are developed and clinically evaluated. This article summarizes the surgical management of colorectal cancer and discusses issues pertaining to postoperative surveillance and the diagnosis and management of local or widespread cancer recurrence.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Anastomose Cirúrgica/métodos , Colectomia/efeitos adversos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Criocirurgia , Humanos , Hipertermia Induzida/métodos , Lasers , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Vigilância da População
10.
Cancer Res ; 56(20): 4724-7, 1996 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-8840990

RESUMO

The purpose of this study was to determine the effect of route of hepatic administration of drug on the regional pharmacokinetics and systemic exposure of 5-fluorouracil (FUra) and 5-bromo-2-deoxyuridine (BrdUrd). A total of 13 mixed-breed male and female dogs were used in these acute studies. Each dog was administered hepatic arterial and portal venous infusions of a single drug, in a cross-over fashion, at two dose rates for a total of four sequential infusions. BrdUrd was studied at 0.250 and 0.500 micromol/min/kg, and FUra was studied at 0.125 and 0.500 micromol/min/ kg. Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (ie., gastroduodenal artery, portal vein, hepatic vein, and femoral artery), perfusion rates in hepatic artery and portal vein were measured, and hepatic extraction (as opposed to extraction across the splanchnic region) was directly assessed. BrdUrd and FUra were found to be highly extracted across the liver (E(H) > or = 0.65) at the regional dose rates studied, resulting in low values for the fraction of drug escaping presystemic hepatic elimination (F(H) < or = 0.35). In addition, the regional kinetics (ie., hepatic extraction, fraction escaping first-pass elimination in the liver, and hepatic clearance) and systemic exposure (i.e., CFA) of FUra and BrdUrd were not significantly different following hepatic arterial versus portal venous infusions of drug. Thus, it appears that regional chemotherapy may be applied to halogenated pyrimidines following hepatic arterial, portal venous, and alternating regional dosing routes with no additional risk of systemic toxicity.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Bromodesoxiuridina/farmacocinética , Fluoruracila/farmacocinética , Fígado/metabolismo , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Bromodesoxiuridina/administração & dosagem , Cães , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Infusões Intra-Arteriais , Infusões Intravenosas , Fígado/irrigação sanguínea , Masculino , Veia Porta , Fluxo Sanguíneo Regional
11.
Dig Dis ; 14(3): 180-91, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8861525

RESUMO

Primary sclerosing cholangitis is a chronic cholestatic disease that may ultimately progress to hepatic parenchymal dysfunction and death from premature liver failure. Symptomatic patients should undergo radiological evaluation to exclude secondary causes of cholangitis and to evaluate the extent and location of biliary ductal disease. A percutaneous liver biopsy is advisable in any patient with clinical or biochemical evidence of cirrhosis. Patients with diffuse ductal involvement should initially receive medical treatment, preferably in a center conducting prospective clinical trials. Liver transplantation should be considered the initial procedure in primary sclerosing cholangitis patients with diffuse ductal involvement, complications of cirrhosis or deteriorating liver function. Nontransplant procedures should be restricted to symptomatic patients with a dominant extrahepatic stricture. In properly selected patients, effective and durable palliation of symptoms can be anticipated with biliary enteric drainage. Many currently available techniques obviate the need for longterm transanastomotic stenting, thus minimizing the risk of recurrent cholangitis and the need for repeated tube changes. These patients may also be candidates for percutaneous or endoscopic balloon cholangioplasty. Liver transplantation should also be considered in patients with a dominant stricture and histologic evidence of biliary cirrhosis or hepatic deterioration following a nontransplant procedure.


Assuntos
Colangite Esclerosante/cirurgia , Cateterismo , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/terapia , Humanos , Transplante de Fígado , Stents
12.
Cancer Res ; 55(17): 3687-91, 1995 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-7641176

RESUMO

Preclinical and clinical data suggest that the combination of hepatic arterial bromodeoxyuridine (BrdUrd), a thymidine analogue radiation sensitizer, and high-dose three-dimensional conformal radiation therapy offer a high potential for improving the local control of intrahepatic cancers. A key step in the design of a successful protocol is to determine in patients the conditions for BrdUrd administration that would be expected to produce selective radiosensitization of the tumor. Therefore, we designed a clinical trial to assess BrdUrd incorporation into the DNA of hepatic colorectal metastases and normal liver after a 7-day continuous BrdUrd infusion at a dose rate of 25 mg/kg/day (the maximal tolerated dose for a 14-day infusion) for patients undergoing laparotomy for either resection of liver metastases or hepatic arterial catheter and pump placement. Thirteen patients were entered into this study. We found that the average replacement of thymidine by BrdUrd in the tumor and normal liver were 11.6 +/- 1.2% and 1.1 +/- 0.2%, respectively. This extent of incorporation would be expected to produce a single fraction radiation enhancement of 1.5 in the tumor without detectable sensitization of the normal liver. Immunohistochemical staining for BrdUrd revealed heterogeneity of incorporation with a range of approximately 60-80% of the cells labeled in different regions of the specimens. These findings suggest that hepatic arterial BrdUrd given at this dose and schedule has a high likelihood of producing clinically significant radiosensitization for patients with hepatic metastases from colorectal cancer. Furthermore, the demonstrated selectivity of tumor perfusion that can be obtained with hepatic arterial infusion combined with the high proliferative rate of colorectal metastases (versus normal liver) suggests that these patients may be good candidates for tumor-directed gene transfer therapy by using regionally delivered retroviral vectors.


Assuntos
Bromodesoxiuridina/metabolismo , Neoplasias Colorretais , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Adulto , Idoso , Bromodesoxiuridina/administração & dosagem , DNA/metabolismo , DNA de Neoplasias/metabolismo , Feminino , Seguimentos , Artéria Hepática , Humanos , Infusões Intra-Arteriais/efeitos adversos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade
13.
Pancreas ; 10(4): 331-7, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7792288

RESUMO

Pancreatic abscess remains a potentially lethal disease. Efforts to relate outcome to the severity of associated pancreatitis or the type of surgical drainage employed have yielded conflicting results. This study was designed to test the validity of traditional prognostic criteria in the clinical setting of pancreatic abscess and to determine whether the technique of surgical drainage employed correlated with survival. The records of 40 consecutive patients with pancreatic abscess were reviewed. In each case the diagnosis was confirmed by operation. Prognostic factors analyzed included number of Ranson criteria, etiology, type, and number of microorganisms isolated, extent of abscess, time to diagnosis and operation, and technique of surgical drainage. Of the 11 Ranson criteria evaluated, only an elevation in blood urea nitrogen > 5 mg/dl correlated with decreased survival (p < 0.001). Polymicrobial abscesses (three or more organisms) resulted in a higher mortality than abscesses where fewer than three organisms were isolated (45.4 vs 13.8%; p < 0.05). Intraperitoneal extension of the abscess was associated with an increased mortality rate compared to those confined to the retroperitoneum (57.1 vs 15.2%; p < 0.01). In patients requiring unplanned reexploration, mortality was significantly increased (42.9 vs 11.5%; p < 0.05). The technique of surgical drainage employed (open versus closed) did not influence overall mortality (23.5 vs 21.7%; p = NS). Extent of disease at operation, polymicrobial abscess, reexploration for persistent or recurrent disease, and deterioration in renal function were all predictive of increased mortality in cases of pancreatic abscess.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Abscesso/cirurgia , Pancreatopatias/cirurgia , Abscesso/microbiologia , Abscesso/mortalidade , Adulto , Idoso , Nitrogênio da Ureia Sanguínea , Drenagem/métodos , Enterobacter/isolamento & purificação , Enterococcus faecalis/isolamento & purificação , Escherichia coli/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/microbiologia , Pancreatopatias/mortalidade , Prognóstico , Reoperação , Estudos Retrospectivos , Staphylococcus/isolamento & purificação , Fatores de Tempo
14.
Am Surg ; 60(7): 466-71; discussion 472, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8010559

RESUMO

Liver cell adenomas are benign, rare tumors that occur primarily in women with a history of oral contraceptive use. Surgical treatment is recommended to reduce the risk of sudden, unpredictable hemorrhage or malignant transformation, but mortality rates of 5 to 8 per cent are reported for major hepatic resections. This report summarizes an experience of eight patients with liver cell adenoma treated by enucleation or resection, alone or combined with hepatic vascular exclusion (HVE). The latter technique, originally described in the mid-1960s, markedly reduces operative blood loss associated with hepatic resection. All eight patients were women of child-bearing age, and seven reported previous oral contraceptive use. The majority of patients were asymptomatic at the time of presentation. Six patients (75%) had a single adenoma and the remaining two had multiple lesions. HVE was used successfully in four patients with no perioperative mortality and reduced by nearly 50 per cent the intraoperative blood loss compared to conventional hepatic resection (1635 mL versus 3875 mL, respectively). Six evaluable patients were followed for an average of 65 months, with no evidence of liver dysfunction or adenoma recurrence. Enucleation of liver cell adenoma appears to be a safe alternative to formal hepatic resection and provides excellent long-term results. HVE markedly reduces operative blood loss, has no adverse effect on metabolic function, decreases the potential health risk associated with transfusion, and should be used whenever possible.


Assuntos
Adenoma de Células Hepáticas/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adenoma de Células Hepáticas/induzido quimicamente , Adenoma de Células Hepáticas/diagnóstico por imagem , Adulto , Perda Sanguínea Cirúrgica , Anticoncepcionais Orais/efeitos adversos , Feminino , Humanos , Fígado/irrigação sanguínea , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
15.
Gastroenterol Clin North Am ; 23(2): 345-69, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8070916

RESUMO

Bariatric surgery is performed for clinically severe obesity and includes jejunoileal bypass, which is designed to produce weight loss through malabsorption, and the gastric restrictive operations--gastric bypass, gastrogastrostomy, and gastroplasty--which produce weight loss through restriction of volume of intake. Patients have problems after bariatric operations because of knowledge deficits; attitudinal, social, and psychologic influences; and anatomic and physiologic effects of these operations. Specific difficulties specific to the type of bariatric operation may arise. Although certain complications may be averted with nonoperative therapy, reversal of the operation may be required for others.


Assuntos
Derivação Gástrica , Gastroplastia , Obesidade Mórbida/cirurgia , Feminino , Derivação Gástrica/psicologia , Gastroplastia/psicologia , Humanos , Complicações Pós-Operatórias
16.
Cancer Res ; 54(8): 2121-4, 1994 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-8174116

RESUMO

This investigation was undertaken to determine the pharmacokinetic parameters relevant to hepatic arterial (HA) infusion of 5-bromo-2'-deoxyuridine (BrdUrd) and to ascertain the maximum tolerated dose and related toxicities of BrdUrd administered as a 14-day HA infusion. In the pharmacokinetic study, 6 patients received a 2-h i.v. infusion (to steady-state) of BrdUrd at each of 5 escalating dose rates (10 to 160 mg/kg/day) with simultaneous blood sampling for BrdUrd levels from HA and hepatic venous catheters. Dose dependent HA and hepatic venous drug levels, total body clearance, hepatic extraction, and estimated regional exposure advantage were determined. The total body clearance of BrdUrd was high and dose rate dependent, falling from 3340 ml/min with a 10-mg/kg/day infusion to 2180 ml/min at a 160-mg/kg/day dose rate. Hepatic extraction was high and dose rate dependent as well, declining from 80% extraction at 10 mg/kg/day to 68% at 160 mg/kg/day. The calculated estimate for the exposure advantage achievable with HA as compared with i.v. infusion reflects the dose rate dependence of total body clearance and hepatic extraction and decreases from a 70-fold advantage at 10 mg/kg/day to a 30-fold advantage at 160 mg/kg/day. In the Phase I study aimed at determining the maximum tolerated dose, successive groups of 3 patients were administered continuous HA infusions for 14 days at escalated BrdUrd dose rates (5, 10, 15, 25, and 35 mg/kg/day) in order to ascertain dose-limiting toxicity. The maximum tolerated dose of BrdUrd for a 14-day continuous HA infusion was found to be 35 mg/kg/day with reversible thrombocytopenia as the sole dose-limiting toxicity. Skin and other toxicities were infrequent, minor, reversible, and non-dose dependent. No hepatic toxicity was detected despite direct drug infusion into the liver. The high total body clearance and hepatic extraction of BrdUrd substantiate its administration via the hepatic artery as a means to achieve higher exposure with intrahepatic tumors than can be obtained by systemic administration. Despite higher hepatic exposures, no hepatic toxicity was noted, and readily reversible systemic toxicity (thrombocytopenia) was dose limiting for the 14-day continuous HA infusion. Thus, HA infusion of the potent radiosensitizer BrdUrd is both pharmacokinetically rational and well tolerated.


Assuntos
Bromodesoxiuridina/farmacocinética , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Bromodesoxiuridina/administração & dosagem , Bromodesoxiuridina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Neoplasias da Vesícula Biliar/sangue , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/sangue , Masculino , Matemática , Pessoa de Meia-Idade
19.
Am J Surg ; 165(1): 81-7; discussion 87-8, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8418704

RESUMO

The purpose of this study was to determine whether delayed computed tomography (DCT) of the liver would more accurately detect hepatic malignancy when compared with bolus contrast-enhanced dynamic computed tomography (BCDCT). Fifty-one patients who required operation for intra-abdominal malignancy (92% with colorectal cancers) underwent preoperative BCDCT followed by DCT. At operation, palpation and intraoperative ultrasound (IOUS) examination of the liver were performed for localization and biopsy of tumor nodules. The standard for diagnosis was defined for this study as the combined results of IOUS, palpation, and biopsy. The sensitivities of BCDCT and DCT for hepatic metastases were 50% and 54%, respectively, with a corresponding specificity of 72% for each. DCT demonstrated no significant improvement over BCDCT in the detection of individual hepatic lesions. The sensitivity of palpation for the detection of metastases was 82%, equal to that of IOUS. Both palpation and IOUS were significantly superior to BCDCT or DCT in excluding false-positive and false-negative results (p < 0.001). IOUS failed to identify surface lesions less than 1.0 cm in diameter (sensitivity: 40%). Conversely, palpation was limited in the detection of subsurface tumors less than 1.0 cm in diameter (sensitivity: 33%). Combined IOUS and palpation were significantly more accurate in the detection of hepatic metastases than any single modality that was evaluated (p < 0.001).


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Iotalamato de Meglumina , Laparotomia , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Palpação , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia
20.
Clin Ther ; 14(1): 97-109, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1576632

RESUMO

A multicenter, open-label randomized trial was conducted to evaluate the efficacy and tolerability of monotherapy with imipenem-cilastatin (I-C) compared with combination therapy with clindamycin and an aminoglycoside (C+A) for treatment of 117 patients with serious intra-abdominal infections. Fifty-three patients (45%) received I-C and 64 patients (55%) received C+A. The overall clinical success rate was 96.2% for the I-C patients and 92.2% for the C+A patients. Clinical failure rates were 3.8% and 7.8%, respectively (P = NS). Eradication or suppression of pathogens was observed in 81.8% and 82.2% of patients, respectively. Uniform bacteriologic response was observed among all infection subgroups. Fourteen of 145 patients experienced adverse symptoms, including six of 66 (9.1%) monotherapy patients and eight of 79 (10.1%) combination-therapy patients (P = NS). The results of this study demonstrate that I-C monotherapy was as effective as C+A combination therapy for the treatment of serious intra-abdominal infections, regardless of the site or severity of infection or the clinical status of the patient. Both regimens also were found to be comparable in tolerability.


Assuntos
Abdome/microbiologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Cilastatina/uso terapêutico , Clindamicina/uso terapêutico , Imipenem/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos , Antibacterianos/efeitos adversos , Infecções por Bacteroides/tratamento farmacológico , Cilastatina/efeitos adversos , Clindamicina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Imipenem/efeitos adversos , Infecções por Klebsiella/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estreptocócicas/tratamento farmacológico
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