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Biomedical subjects

D B Evans

Publications and source records attributed to D B Evans.

At least 91 records · Page 5Linked to original sources
PubMed1998

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Pancreaticoduodenectomy is performed on carefully selected patients as part of a protocol-based clinical research program emphasizing the importance of multimodality management for patients with potentially resectable adenocarcinoma of the pancreatic head. Treatment schemas emphasize the importance of minimizing toxicity and treatment duration, while attempting to improve therapeutic efficacy. Cytotoxicity is enhanced by combining radiation therapy with more potent radiation-sensitizing agents. Because of the high incidence of liver metastases, systemic therapy is continued after chemoradiation and surgery with systemic agents of low toxicity directed at specific molecular events involved in pancreatic tumorigenesis such as inhibition of angiogenesis, induction of apoptosis, or arrest of the cell cycle.

Adenocarcinoma↗
PubMed1998

Primary pancreatic lymphoma.

BACKGROUND: Primary pancreatic lymphoma is a rare neoplasm that may be confused with pancreatic adenocarcinoma. We reviewed retrospectively our contemporary experience with this disease to define more clearly the clinical presentation of this disease and the proper role for percutaneous fine-needle aspiration biopsy and surgery. METHODS: From 1980 to 1995, 11 patients with primary pancreatic lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Patient demographics, radiographic studies, fine-needle aspiration biopsy findings, operative procedures, and other treatment data were reviewed. RESULTS: The median age of the 11 patients was 64 years (range, 37 to 74 years). Abdominal pain was the most common symptom at presentation. Five patients had an elevated lactate dehydrogenase level, and only two patients had hyperbilirubinemia. Computed tomography scan demonstrated encasement of the superior mesenteric artery or superior mesenteric-portal vein confluence in six patients. Seven patients underwent computed tomography-guided fine-needle aspiration; five had findings of lymphoma. Two patients underwent distal pancreatectomy and splenectomy, and one underwent pancreaticoduodenectomy. All patients were treated with combination chemotherapy, and seven received radiotherapy. Only two patients have died of disease (12 and 16 months after diagnosis) at a median follow-up time of 67 months. CONCLUSIONS: In the majority of patients, pancreatic lymphoma can be distinguished from pancreatic adenocarcinoma on the basis of symptoms, laboratory and radiographic findings, and fine-needle aspiration biopsy results. Once the diagnosis is established, all patients should undergo systemic chemotherapy followed by involved-field radiotherapy if the tumor has not been resected.

Adult↗
PubMed1997

The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma.

Human cathepsin K is a novel cysteine protease previously reported to be restricted in its expression to osteoclasts. Immunolocalization of cathepsin K in breast tumor bone metastases revealed that the invading breast cancer cells expressed this protease, albeit at a lower intensity than in osteoclasts. In situ hybridization and immunolocalization studies were subsequently conducted to demonstrate cathepsin K mRNA and protein expression in samples of primary breast carcinoma. Expression of cathepsin K mRNA was confirmed by reverse transcription PCR and Southern analysis in a number of human breast cancer cell lines and in primary human breast tumors and their metastases. As this protease is known to degrade extracellular matrix, including bone matrix proteins, it is possible that cathepsin K may contribute to the invasive potential of breast cancer cells, including those that metastasize to bone. Thus, cathepsin K may be a potential target leading to the design of novel drugs for cancer therapy.

Blotting, Southern↗
PubMed1997

Induction of p21waf1 expression and growth inhibition by transforming growth factor beta involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells.

The tumor suppressor gene deleted in pancreatic cancer locus 4 (DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. DPC4 was found to be homologous to Smad4 and may function as a transcription factor in the transforming growth factor beta (TGF-beta) receptor-mediated signal transduction pathway. We have investigated the role of DPC4 in the TGF-beta receptor-mediated signal transduction cascade in five human pancreatic cancer cell lines (Panc-1, MDAPanc-28, HS766T, Capan-1, and MiaPaCa-2). Our results demonstrate that the loss of responsiveness to TGF-beta-induced growth inhibition correlates with the loss of expression of DPC4. We have shown that TGF-beta induces p21waf1 expression in Panc-1 cells, whereas no induction of p21waf1 expression by TGF-beta was detected in the other four cell lines lacking either DPC4 expression or the TGF-beta type II receptor. No increase in p21waf1 mRNA stability was observed after treatment with TGF-beta, which suggests that the induction of p21waf1 in Panc-1 cells is transcriptionally regulated by TGF-beta. Our data also demonstrate that the expression of DPC4 is directly involved in TGF-beta-mediated induction of the 3TP-lux reporter gene, which contains a known TGF-beta-inducible plasminogen activator inhibitor promoter. These data suggest that: (a) TGF-beta-mediated induction of p21waf1 and subsequent growth inhibition require the expression of DPC4; (b) p21waf1 is a downstream target gene of DPC4; and (c) transfection of the DPC4 gene restores the TGF-beta-inducible gene expression. Inactivation of the tumor suppressor gene DPC4 and other components of the TGF-beta signal cascades may abolish one of the key negative controls of cell proliferation in pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed1997

Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma.

BACKGROUND: The prognosis for patients with extrahepatic bile duct cancer remains poor. The purpose of this study was to evaluate our initial results with preoperative chemoradiation for extrahepatic cholangiocarcinoma, in the context of our experience with conventional treatment of this disease over the past 13 years. METHODS: From 1983 through 1996, analysis of all patients treated for extrahepatic cholangiocarcinoma was performed. RESULTS: Of 91 total patients, 51 had unresectable disease and 40 underwent resection. Median survival was significantly different for patients who underwent resection (22.2 months) versus those treated palliatively (10.7 months; P <0.0001). Nine patients underwent preoperative chemoradiation (5 perihilar, 4 distal) prior to resection. Three patients in the preoperative chemoradiation group had a pathologic complete response, while the remainder showed varying degrees of histologic response to treatment. The rate of margin-negative resection was 100% for the preoperative chemoradiation group versus 54% for the group who did not receive preoperative chemoradiation (P <0.01). There were no major intra-abdominal complications in the patients treated with preoperative chemoradiation. CONCLUSIONS: These results suggest that preoperative chemoradiation for extrahepatic bile duct cancer can be performed safely, produces significant antitumor response, and may improve the ability to achieve tumor-free resection margins. Additional trials of preoperative chemoradiation are warranted.

Adult↗
PubMed1997

The multidisciplinary structured clinical instruction module as a vehicle for cancer education.

BACKGROUND: The Structured Clinical Instruction Module (SCIM) modifies the Objective Structured Clinical Examination (OSCE) for teaching purposes. This study determined the effectiveness of a breast cancer SCIM in enhancing residents' clinical skills. METHODS: Twenty-five residents, 15 faculty members, and 12 breast cancer patients (simulated and actual) participated in the multistation, multidisciplinary SCIM. Afterward, faculty members, residents, and patients evaluated the SCIM. Residents completed an 18-item self-assessment of their skills before and after the SCIM. RESULTS: All residents, faculty members, and patients rated the SCIM as either outstanding or above average as an educational experience. The residents' self-assessments of their skills were significantly higher after the SCIM than before. CONCLUSIONS: This study shows that residents are aware of their deficiencies in breast cancer management. The SCIM provides an excellent format for residents to improve their clinical skills.

Attitude of Health Personnel↗
PubMed1997

Correcting the fit of implant-retained restorations by electric discharge machining.

Discrepancies in the passive fit of an implant-retained restoration to its supporting abutments are occasionally encountered during the clinical try-in and evaluation appointment. Frequently, the framework must then be sectioned and meticulously soldered to achieve accurate seating of the prosthesis. Furthermore, it may be necessary to remove the restoration's existing esthetic porcelain or resin veneer to improve access for soldering. These traditional corrective procedures are likely to require another patient appointment and significant laboratory time. This article describes the alternative use of electric discharge machining to correct the fit of implant-retained restorations that display incomplete seating during the clinical try-in appointment.

Dental Polishing↗
PubMed1997

Improving residents' clinical skills with the structured clinical instruction module for breast cancer: results of a multiinstitutional study. Breast Cancer Education Working Group.

BACKGROUND: The purpose of this study was to determine, in a multiinstitutional setting, the effectiveness of the structured clinical instruction module (SCIM) as an instructional format for surgical residents. METHODS: The breast cancer SCIM is an abbreviated (3-hour) clinical skills course that places residents in realistic clinical settings. The curriculum encompasses all aspects of breast cancer patient assessment. The SCIM was administered to 137 residents at five institutions. Sixty-six faculty members and 52 patients participated. All participants were surveyed with multiitem questionnaires. The residents were also asked to perform a self-assessment of their skills before and after the SCIM. RESULTS: The SCIM was delivered at all institutions without difficulty. All participants rated the SCIM highly (from "above average" to "outstanding"). Mean ratings (on a 5-point scale) for the overall effectiveness of the SCIM as an educational format follow: [table: see text] The pretest mean (on a 5-point scale) on the self-assessment was 2.46 ("less than competent"); the posttest mean was 3.54 ("more than competent") (p < 0.0001). CONCLUSIONS: Residents are acutely aware of their deficiencies in understanding breast cancer. The SCIM is a standardized, reproducible, portable, and effective educational vehicle.

Breast Neoplasms↗
PubMed1997

Should governments subsidize the use of insecticide-impregnated mosquito nets in Africa? Implications of a cost-effectiveness analysis.

Recent large-scale field trials show that mosquito nets impregnated with insecticide can substantially reduce all-cause mortality in children in malaria-endemic areas in Africa. This paper considers the cost-effectiveness of impregnated nets, initially from the perspective of a government programme which would distribute nets free of charge and organize and fund re-impregnation on an annual basis. The calculations show that with the reductions in all-cause mortality observed in the trials, complete government subsidy of nets through a vertical programme would represent an efficient use of scarce resources for most combinations of assumptions. However, alternative ways of financing and organizing the use of impregnated nets are also possible and may be more cost-effective than vertical delivery. Distribution of nets and insecticide might be less costly than required for a vertical programme by integrating delivery with other types of government health programmes, with private sector delivery systems for other types of products, or with government systems developed for other sectors such as agriculture. Further, not all the costs need to be met by governments, as costs could be shared with donors, NGOs and the beneficiaries. The major conclusion is that impregnated nets would save a large number of lives in malaria endemic areas, they are an efficient use of scare resources, and ways of encouraging their use need to be developed and tested.

Africa↗
PubMed1997

Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease.

OBJECTIVE: This study was conducted to determine whether the perioperative administration of octreotide decreases the incidence of pancreatic anastomotic leak after pancreaticoduodenectomy for malignancy. SUMMARY BACKGROUND DATA: Three multicenter, prospective, randomized trials concluded that patients who receive octreotide during and after pancreatic resection have a reduction in the total number of complications or a decreased incidence of pancreatic fistula. However, in the subset of patients who underwent pancreaticoduodenectomy for malignancy, either no analysis was performed or no benefit from octreotide could be demonstrated. METHODS: A single-institution, prospective, randomized trial was conducted between June 1991 and December 1995 involving 120 patients who were randomized to receive octreotide (150 microg subcutaneously every 8 hours through postoperative day 5) or no further treatment after pancreaticoduodenectomy for malignancy. The surgical technique was standardized, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa or invagination technique. RESULTS: The two patient groups were similar with respect to patient demographics, treatment variables, and histologic diagnoses. The rate of clinically significant pancreatic leak was 12% in the octreotide group and 6% in the control group (p = 0.23). Perioperative morbidity was 30% and 25%, respectively. Patients who underwent reoperative pancreaticoduodenectomy had an increased incidence of pancreatic anastomotic leak, whereas those who received preoperative chemoradiation had a decreased incidence of pancreatic anastomotic leak. CONCLUSIONS: The routine use of octreotide after pancreaticoduodenectomy for malignancy cannot be recommended.

Adult↗
PubMed1997

Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas.

PURPOSE: The effects of preoperative versus postoperative fluorouracil (5-FU)-based chemotherapy and irradiation on treatment toxicity, duration of treatment, tumor recurrence, and survival were compared in patients who underwent potentially curative therapy for adenocarcinoma of the pancreatic head during a 5-year period. METHODS: From July 1990 to July 1995, 142 patients with localized adenocarcinoma of the pancreatic head deemed resectable on the basis of radiographic images were treated with curative intent using a multimodality approach involving either preoperative or postoperative chemoradiation. Patients with biopsy confirmation of adenocarcinoma and a low-density mass in the pancreatic head identified by computed tomography (CT) received preoperative chemoradiation. Patients without a mass on CT or in whom the preoperative biopsy was negative underwent pancreaticoduodenectomy with planned postoperative chemoradiation. Protocol-based preoperative chemoradiation consisted of external-beam irradiation at a dose of 50.4 Gy (standard fractionation; 1.8 Gy/d, 5 d/wk) or 30 Gy (rapid fractionation; 3 Gy/d, 5 d/wk) combined with continuous infusion 5-FU (300 mg/m2/d, 5 d/wk). Postoperative chemoradiation combined 50.4 Gy of external-beam irradiation (standard fractionation) with continuous-infusion 5-FU. RESULTS: No patient who received preoperative chemoradiation experienced a delay in surgery because of chemoradiation toxicity, but six of 25 eligible patients (24%) did not receive postoperative chemoradiation because of delayed recovery after pancreaticoduodenectomy. No significant differences in toxicities from chemoradiation were observed between groups. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly (P < .01) shorter duration of treatment (median, 62.5 days) compared with patients who received postoperative chemoradiation (median, 98.5 days) or standard-fractionation preoperative chemoradiation (median, 91.0 days). At a median followup of 19 months, no significant differences in survival were observed between treatment groups. No patient who received preoperative chemoradiation and pancreaticoduodenectomy experienced a local recurrence; peritoneal (regional) recurrence occurred in 10% of these patients. Local or regional recurrence occurred in 21% of patients who received pancreaticoduodenectomy and postoperative chemoradiation. CONCLUSION: Delivery of preoperative and postoperative chemoradiation in patients who underwent potentially curative pancreaticoduodenectomy for adenocarcinoma of the pancreatic head resulted in similar treatment toxicity, patterns of tumor recurrence, and survival. Rapid-fractionation preoperative chemoradiation ensured the delivery of all components of therapy to all eligible patients with a significantly shorter duration of treatment than with standard-fractionation chemoradiation given either before or after pancreaticoduodenectomy. Prolonged recovery after pancreaticoduodenectomy prevents the delivery of postoperative adjuvant chemoradiation in up to one fourth of eligible patients.

Adenocarcinoma↗
PubMed1997

Gastric cancer surgical practice guidelines. Gastric Cancer Practice Guideline Committee.

The data described above suggest that the current management of gastric carcinoma requires a surgical resection. Identification of the number of lymph nodes that may be involved with cancer is an important prognosticator. Resection of involved lymph nodes is likely to decrease the morbidity of locoregional recurrence. However, this has not been adequately addressed in the studies performed to date. Nonetheless, accurate staging is an essential goal of the primary therapy of gastric carcinoma. The limits of resection for a gastric cancer are outlined in the guidelines (see page 1068). Administration of adjuvant therapy, such as chemotherapy or radiation therapy, remains controversial and is the subject of ongoing clinical research. Until a prospective, randomized trial demonstrates a significant improvement in survival, there remains little or no basis for the addition of adjuvant therapy outside the context of a clinical trial.

Carcinoma↗