Biomedical subjects

D B Evans

Publications and source records attributed to D B Evans.

At least 73 records · Page 4Linked to original sources

PubMed1999

Malaria epidemiology and economics: the effect of delayed immune acquisition on the cost-effectiveness of insecticide-treated bednets.

An understanding of the epidemiology of a disease is central in evaluating the health impact and cost-effectiveness of control interventions. The epidemiology of life-threatening malaria is receiving renewed interest, with concerns that the implementation of preventive measures such as insecticide-treated bednets (ITNs) while protecting young children might in fact increase the risks of mortality and morbidity in older ages by delaying the acquisition of functional immunity. This paper aims to illustrate how a combined approach of epidemiology and economics can be used to (i) explore the long-term impact of changes in epidemiological profiles, and (ii) identify those variables that are critical in determining whether an intervention will be an efficient use of resources. The key parameters for determining effectiveness are the protective efficacy of ITNs (reduction in all-cause mortality), the malaria attributable mortality and the increased malaria-specific mortality risk due to delays in the acquisition of functional immunity. In particular, the analysis demonstrates that delayed immune acquisition is not a problem per se, but that the critical issue is whether it occurs immediately following the implementation of an ITN programme or whether it builds up slowly over time. In the 'worst case' scenario where ITNs immediately increase malaria-specific mortality due to reduced immunity, the intervention might actually cost lives. In other words, it might be better to not use ITNs. On the other hand, if reduced immunity takes two years to develop, ITNs would still fall into the category of excellent value for money compared to other health interventions, saving a year of life (YLL) at a cost of between US$25-30. These types of calculations are important in identifying the parameters which field researchers should be seeking to measure to address the important question of the net impact of delaying the acquisition of immunity through preventive control measures.

Adolescent↗

PubMed1999

Screening for MEN1 mutations in patients with atypical endocrine neoplasia.

BACKGROUND: Most patients from typical multiple endocrine neoplasia type 1 (MEN1) kindreds harbor mutations in the MEN-1 gene, MEN1. We hypothesized that some patients with atypical endocrine neoplasia would also have mutations in MEN1. METHODS: DNA sequencing analysis of mutations in the coding region of MEN1 was performed with genomic DNA obtained from peripheral blood lymphocytes in a total of 21 patients who had: typical MEN1 (n = 8), clinical features suggestive of MEN1 but without a family history of endocrinopathy (n = 7), and atypical endocrine neoplasia and a family history of endocrinopathy suggestive of MEN1 (n = 6). RESULTS: All 8 patients with typical MEN1 had mutations in MEN1. None of the 7 patients with features of MEN1, but without a family history of endocrinopathy, had a MEN1 mutation. In contrast, 4 of 6 patients with atypical endocrine neoplasia that included components of MEN1 and a family history of endocrinopathy had mutations in MEN1, including 2 patients with pheochromocytoma. CONCLUSIONS: Genomic mutations in MEN1 may frequently be identified in patients with atypical endocrine neoplasia, especially in the setting of a family history of endocrinopathy. Atypical presentations of MEN1 may include pheochromocytoma.

Adrenal Gland Neoplasms↗

PubMed1999

Surgical strategy for the treatment of medullary thyroid carcinoma.

OBJECTIVE: To evaluate surgical complications, patterns of lymph node metastases, and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent medullary thyroid carcinoma (MTC). SUMMARY BACKGROUND DATA: The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. These data have provided the rationale for surgeons to perform a more extensive lymphadenectomy at the time of initial thyroidectomy and to consider reoperative cervical lymphadenectomy in patients with persistently elevated calcitonin levels after thyroidectomy. METHODS: Forty patients underwent surgery for MTC from 1991 to 1997 (23 sporadic cases, 17 familial cases). Patients were divided into three groups based on whether they had undergone previous thyroidectomy and on the results of standardized staging studies performed after referral to the authors' institution. Group 1 (11 patients) had received no previous surgery; group 2 (13) underwent thyroidectomy before referral and had an elevated calcitonin level without radiologic evidence of local regional or distant metastases; and group 3 (16) underwent thyroidectomy before referral and had an elevated calcitonin level with radiologic evidence of local-regional recurrence. The central neck compartment was dissected in all patients; preoperative staging and the extent of previous surgery dictated the need for lateral (modified radical) neck dissection. After primary or reoperative surgery, calcitonin levels were assessed. RESULTS: All patients had major reductions in postoperative calcitonin levels. Seven (29%) of 24 patients in groups 1 and 2 achieved normal calcitonin values compared with only 1 (6%) of 16 in group 3. Postoperative complications included seven cases (17%) of permanent hypoparathyroidism; five (71%) of these occurred in group 3. There were no iatrogenic recurrent laryngeal nerve injuries; one patient required recurrent nerve resection to achieve complete tumor extirpation. At a median follow up of 35 months, local recurrence was documented in 5 (13%) of 40 patients. CONCLUSIONS: Compartment-oriented lymphadenectomy performed early in the course of MTC is safe and may return calcitonin levels to normal in up to 25% of carefully selected patients. However, reoperation for bulky cervical disease (group 3) rarely results in normal calcitonin levels and is associated with a high incidence of permanent hypoparathyroidism.

Adolescent↗

PubMed1999

Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma.

PURPOSE: Patients with local-regional gastric carcinoma have a low rate of curative resection (R0) because of the advanced stage at diagnosis and suboptimal clinical staging. This study was designed to improve clinical staging with the use of laparoscopy and endoscopic ultrasonography (EUS) and to improve R0 resection rates and tolerance by delivering all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. PATIENTS AND METHODS: All patients with histologic proof of localized adenocarcinoma of the stomach underwent a staging laparoscopy before registration. EUS was performed when feasible. The intention was to administer up to five courses of preoperative chemotherapy consisting of fluorouracil (500 mg/m(2)/d as a continuous infusion on days 1 through 5 and as a bolus on days 12 and 19), interferon alfa-2b (3 million units subcutaneously three times a week for 3 weeks), and cisplatin (15 mg/m(2)/d as a bolus on days 1 through 5). After chemotherapy, surgery was attempted to remove the primary and regional lymph nodes. Clinical response and EUS staging were correlated with surgical pathology. The feasibility of this approach, resection rates, patient survival, and patterns of failure also were assessed. RESULTS: All 30 patients enrolled were assessed for toxicity, response, and survival. Nineteen men and 11 women were enrolled. The median number of courses delivered per patient was three (range, one to five courses). Fourteen patients (47%) received all five preoperative courses of chemotherapy. The overall clinical response rate was 34%. Twenty-nine patients (97%) underwent attempted resection. Twenty-five (83%) had an R0 resection. Two patients (7%) had no evidence of carcinoma in the surgical specimen, and three had only microscopic carcinoma (>/= 90% necrosis). Posttreatment EUS findings did not correlate well with surgical pathology. The median duration of follow-up was 30 months (range, 5 months to 65+ months). The median survival time for 30 patients, calculated by the Kaplan-Meier method, was 30 months (range, 5 months to 65+ months). There were no cases of grade 4 toxicity. CONCLUSION: It is feasible to administer prolonged preoperative therapy in patients with potentially resectable gastric carcinoma. Enhanced staging with laparoscopy and EUS helped in proper selection of patients and better characterization of the stage.

Adenocarcinoma↗

PubMed1999

Shear bond strength of composite resin and amalgam adhesive systems to dentin.

PURPOSE: To determine the effects of several multi-purpose dental adhesive systems on the shear bond strength of both composite resin (Herculite XRV) and amalgam (Tytin) to dentin. MATERIALS AND METHODS: 160 extracted human molar teeth were randomly assigned to 16 treatment groups (n = 10/group), embedded in resin, and ground flat on both the occlusal and apical surfaces to expose a 3.0 mm thickness of dentin. In each specimen, a 3.18 mm diameter channel was drilled through the dentin perpendicular to the ground surface. The cylindrical preparations were treated with one of seven adhesive systems or one of two controls (37% H3PO4 or Copalite varnish) according to manufacturers' recommendation, then restored with either composite resin or amalgam. Specimens were thermocycled and subjected to a punch-out shear force using a materials testing machine. RESULTS: All examined multi-purpose adhesive systems provided increased shear bond strength in comparison to the controls. Although the individual performance of each adhesive system varied with specific restorative materials, OptiBond FL demonstrated the highest mean shear bond strength to both composite resin and amalgam. Mean amalgam shear bond strength was significantly greater than mean composite resin strengths.

Acid Etching, Dental↗

PubMed1999

Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma.

We examined the expression level of several genes that regulate distinct steps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative surgery. The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybridization technique. Down-regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patients alive 28-64 months after surgery. Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, whereas stage, nodal metastasis, and histological type were not. These data show that multiparametric analysis for several metastasis-related genes may allow physicians to assess the metastatic potential and hence predict the clinical outcome of individual patients with resectable pancreatic carcinoma.

Adenocarcinoma↗

PubMed1999

The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells.

Pancreatic adenocarcinoma is a leading cause of adult cancer mortality in the United States. Recent studies have revealed that point mutation of the K-ras oncogene is a common event in pancreatic cancer, and oncogenesis mediated by Ras may also involve activation of Rel/nuclear factor (NF)-kappa B transcription factors. Furthermore, the c-rel member of Rel/NF-kappa B transcription factor family was first identified as a cellular homologue of the v-rel oncogene, suggesting that other members of the Rel/NF-kappa B family are potentially oncogenes. We therefore investigated the possibility that Rel/NF-kappa B transcription factors are activated in pancreatic cancer. Immunohistochemical analysis, Western blot and Northern blot analysis, electrophoretic mobility shift assays, and chloramphenicol acetyltransferase assays were performed to determine RelA activity in human pancreatic adenocarcinomas and normal tissues and nontumorigenic or tumorigenic cell lines. RelA, the p65 subunit of NF-kappa B, was constitutively activated in approximately 67% (16 of 24) of pancreatic adenocarcinomas but not in normal pancreatic tissues. Constitutive RelA activity was also detected in 9 of 11 human pancreatic tumor cell lines but not in nontumorigenic Syrian golden hamster cell lines. I kappa B alpha, a previously identified NF-kappa B-inducible gene, was overexpressed in human pancreatic tumor tissues and cell lines, and RelA activation could be inhibited by curcumin and dominant-negative mutants of I kappa B alpha, raf, and MEKK1. This is the first report demonstrating constitutive activation of RelA in nonlymphoid human cancer. These data are consistent with the possibility that RelA is constitutively activated by the upstream signaling pathway involving Ras and mitogen-activated protein kinases in pancreatic tumor cells. Constitutive RelA activity may play a key role in pancreatic tumorigenesis through activation of its downstream target genes.

Adenocarcinoma↗

PubMed1998

Overexpression of the tumor suppressor gene Smad4/DPC4 induces p21waf1 expression and growth inhibition in human carcinoma cells.

The Smad4/DPC4 protein functions as a key transcription factor in transforming growth factor beta (TGF-beta) signaling pathways. However, the downstream target genes regulated by Smad4/DPC4 have not been identified until now. We previously demonstrated that the loss of TGF-beta-induced p21waf1 expression and growth inhibition correlates with inactivation of the Smad4/DPC4 gene. Now we show that transient overexpression of Smad4/DPC4 can induce p21waf1 expression, specific Smad4 DNA binding activity, SBE4-luc reporter gene activity, and subsequent growth inhibition in Smad4/DPC4-null cells and other carcinoma cells in the presence or absence of TGF-beta. Taken together, these data show that p21waf1 is one of the Smad4/DPC4-regulated downstream target genes and suggest that overexpression of the Smad4/DPC4 gene can bypass TGF-beta receptor activation and reestablish one of the key regulatory controls of cell proliferation.

Carcinoma↗

PubMed1998

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Adjuvant 5-fluorouracil and concurrent radiation may improve survival following complete surgical resection in patients with pancreatic adenocarcinoma. However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevents the timely delivery of postoperative chemoradiation. Therefore, the University of Texas M.D. Anderson Cancer Center (MDACC) has investigated the use of neoadjuvant chemoradiation in potentially resectable pancreatic cancer. We have incorporated a standardized approach to pretreatment staging, operative technique and pathologic evaluation. Our initial experience suggests that preoperative chemoradiation is well tolerated and may reduce loco-regional recurrence. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly shorter duration of treatment compared with patients who received postoperative chemoradiation or standard-fractionation preoperative chemoradiation. New and more potent radiation-sensitizing agents such as gemcitabine may further enhance local control. Novel therapies directed at specific molecular events involved in pancreatic tumorigenesis may be incorporated into preoperative and postoperative regimens to attempt to reduce systemic relapse.

Adenocarcinoma↗

PubMed1998

Gene therapy and pancreatic cancer.

Adenocarcinoma of the pancreas is associated with a short survival due to frequent delays in diagnosis and the lack of effective systemic therapies. Advances in understanding the molecular basis of pancreatic cancer have allowed identification of molecular targets which are amenable to therapeutic intervention. Such targets include p53, K-ras, p16, and DPC-4. Gene therapy involves the transfer of genetic constructs which alter the neoplastic potential of the cancer cell. Vectors used in gene transfer include viral and non-viral methods. Presently, gene therapy of pancreatic cancer is limited to pre-clinical studies using in vitro and in vivo models. However, the initial results from these pre-clinical studies have been encouraging and will form the basis for clinical studies of gene transfer in patients with pancreatic cancer.

Adenocarcinoma↗

PubMed1998

DNA adducts in human pancreatic tissues and their potential role in carcinogenesis.

Pancreas cancer is the fourth and fifth leading cause of cancer death for men and women, respectively, in the United States. Although the etiology of this cancer is poorly understood, smoking and dietary fat have been implicated by epidemiological studies. To test the hypothesis that DNA damage derived from carcinogen exposure and diet is involved in pancreatic carcinogenesis, aromatic and lipid peroxidation-related DNA adducts in 13 normal tissues adjacent to tumor and 20 tumors from pancreatic cancer patients were analyzed by 32P-postlabeling. Normal pancreatic tissues from 5 nonpancreatic cancer patients and 19 healthy organ donors served as controls. To correlate the DNA adduct level with patients' characteristics, information on age, sex, body mass index, and smoking status of pancreatic cancer patients were collected from medical records. A significantly higher level of total DNA adducts was detected in pancreatic cancer patients as compared with controls. The mean level of adducts/10(8) nucleotides in adjacent normal pancreatic tissues from pancreatic cancer patients (A tissues) was 102 +/- 21 compared with 39 +/- 6 and 13 +/- 1 in pancreatic tumor tissues (T tissues) and normal pancreatic tissues from controls (C tissues), respectively. Among the adducts observed, one single aromatic adduct (spot 1) was present in 100, 90, and 0% of the A, T, and C tissues, respectively. Two novel clusters of adducts (spots 2 and 3) were observed in 11 of 13, 12 of 20, and 2 of 24 of A, T, and C tissues, respectively, and the presence of these adducts was positively correlated with smoking status. In addition, the previously defined smoking-related diagonal radioactive zone was detected in three A samples only, although 50% (10 of 20) of the patients with pancreatic cancers in this study were ever smokers. Putative lipid peroxidation-related adducts were detected in all samples examined and were significantly higher in A than in T and C samples. Multiple regression analyses showed that body mass index was positively correlated to the levels of spot 1 and the lipid peroxidation-related adducts in A tissues and the total aromatic adducts in tumors. Smoking was also positively correlated to the level of total adducts. These observations are consistent with previous epidemiological findings and support the hypothesis that DNA damage related to carcinogen exposure and lipid peroxidation is involved in human pancreatic carcinogenesis.

Adult↗

PubMed1998

Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic cancer [seecomments].

BACKGROUND: The p53 tumor suppressor gene is mutated in up to 70% of pancreatic adenocarcinomas. We determined the effect of reintroduction of the wild-type p53 gene on proliferation and apoptosis in human pancreatic cancer cells using an adenoviral vector containing the wild-type p53 tumor suppressor gene. METHODS: Transduction efficiencies of six p53-mutant pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, and PANC-1) were determined using the reporter gene construct Ad5/CMV/beta-gal. Cell proliferation was monitored using a 3H-thymidine incorporation assay, Western blot analysis for p53 expression was performed, and DNA laddering and fluorescence-activated cell sorter analysis were used to assess apoptosis. p53 gene therapy was tested in vivo in a subcutaneous tumor model. RESULTS: The cell lines varied in transduction efficiency. The MIA PaCa-2 cells had the highest transduction efficiency, with 65% of pancreatic tumor cells staining positive for beta-galactosidase (beta-gal) at a multiplicity of infection (MOI) of 50. At the same MOI, only 15% of the CFPAC-1 cells expressed the beta-gal gene. Adenovirus-mediated p53 gene transfer suppressed growth of all human pancreatic cancer cell lines in a dose-dependent manner. Western blot analysis confirmed the presence of the p53 protein product at 48 hours after infection. DNA ladders demonstrated increased chromatin degradation, and fluorescence-activated cell sorter analysis demonstrated a four-fold increase in apoptotic cells at 48 and 72 hours following infection with Ad5/CMV/p53 in the MIA PaCa-2 and PANC-1 cells. Suppression of tumor growth mediated by induction of apoptosis was observed in vivo in an established nude mouse subcutaneous tumor model following intratumoral injections of Ad5/CMV/p53. CONCLUSIONS: Introduction of the wild-type p53 gene using an adenoviral vector in pancreatic cancer with p53 mutations induces apoptosis and inhibits cell growth. These data provide preliminary support for adenoviral mediated p53 tumor suppressor gene therapy of human pancreatic cancer.

Adenocarcinoma↗

PubMed1998

Cell cycle regulation of human pancreatic cancer by tamoxifen.

BACKGROUND: Clinical trials have suggested a survival advantage for selected patients with metastatic pancreatic cancer treated with tamoxifen. We sought to identify the molecular mechanism by which tamoxifen inhibits human pancreatic cancer cell (HPCC) growth. METHODS: HPCCs were grown in tamoxifen and growth inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in cell viability were determined by cell counts. Cell cycle alterations were evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern blot analysis was performed for p21waf1. RESULTS: Tamoxifen inhibited HPCC growth as measured by inhibition of 3H-thymidine incorporation and by the MTT assay. However, there was no decrease in the total number of viable cells after 6 days of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to tamoxifen treatment. CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is an effective inhibitor of HPCC growth in vitro and warrants further in vivo study.

Antineoplastic Agents, Hormonal↗

PubMed1998

Preoperative chemoradiation strategies for localized adenocarcinoma of the pancreas.

Patients who undergo pancreaticoduodenectomy alone for adenocarcinoma of the pancreatic head or uncinate process have a median survival of 12 months, and a high incidence of local tumor recurrence (50%-80%) due to the common finding of positive margins following pathologic evaluation of pancreaticoduodenectomy specimens. The available prospective and retrospective data suggest improved survival duration and local-regional tumor control when pancreaticoduodenectomy is combined with 5-FU-based chemoradiation. However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevent the timely delivery of postoperative chemoradiation. In contrast, chemoradiation delivered prior to pancreaticoduodenectomy is not associated with toxic effects which delay surgery and has not been shown to increase surgical morbidity or mortality. In fact, recent data suggest that pancreaticojejunal anastomotic leaks, the most common major complication following pancreaticoduodenectomy, are decreased in patients who receive preoperative radiation therapy. Current and future multimodality treatment strategies will capitalize on our expanding understanding of tumor growth and metastasis, allowing more effective radiation sensitizing agents to be combined with external-beam irradiation and surgery, followed by the systemic or regional delivery of novel agents that inhibit essential steps in tumor cell growth.

Adenocarcinoma↗

PubMed1998

Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma.

Angiogenesis is essential for growth and metastasis of solid malignancies. In several tumours, tumour vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. To determine if vessel count and VEGF expression are prognostic factors in pancreatic cancer, we examined these parameters in resected tumour specimens from 22 patients who did not receive pre-operative therapy. Paraffin-embedded tumour specimens were immunohistochemically stained for factor VIII (surrogate for vessels) and VEGF. Vessel counts and VEGF expression were evaluated without knowledge of patient outcome. The median follow-up for the entire group had not been reached as of 23.1 months (range 10-69 months). The mean vessel count and VEGF expression were no different between those patients who had recurrences and those who did not. By linear regression analysis, the correlation of VEGF expression with vessel count did not reach statistical significance (P = 0.0685). Survival and time to recurrence were similar in patients with high and low vessel counts and VEGF expression of 1, 2 or 3. Tumour differentiation or lymph node positivity had no effect on either VEGF expression or vessel count. Our data suggest that, in contrast to findings in other solid malignancies, vessel count and VEGF expression are not predictors of survival or recurrence in patients with resectable adenocarcinoma of the pancreas.

Adenocarcinoma↗

PubMed1998

Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head.

BACKGROUND: The survival of patients who underwent pancreaticoduodenectomy with or without en bloc resection of the superior mesenteric-portal vein (SMPV) confluence for adenocarcinoma of the pancreatic head was compared. METHODS: To be considered for surgery, patients were required to fulfil the following computed tomography criteria for resectability: (1) absence of extrapancreatic disease, (2) no evidence of tumour extension to the superior mesenteric artery (SMA) or coeliac axis, and (3) a patent SMPV confluence. Tumour adherence to the superior mesenteric vein (SMV) or SMPV confluence was assessed at operation and en bloc venous resection was performed when necessary to achieve complete tumour extirpation. RESULTS: Seventy-five consecutive patients underwent pancreaticoduodenectomy, 44 without venous resection and 31 with en bloc resection of the SMPV confluence. There were no perioperative deaths in either group; late (more than 6 months) occlusion of the reconstructed SMPV confluence contributed to the death of two patients. Median survival in the 31 patients who required venous resection at the time of pancreaticoduodenectomy was 22 months, and that for the 44 control patients was 20 months (P = 0.25). CONCLUSION: Patients with adenocarcinoma of the pancreatic head who require venous resection during pancreaticoduodenectomy for isolated tumour extension to the SMV or SMPV confluence (in the absence of tumour extension to the SMA or coeliac axis) have a duration of survival no different from that of patients who undergo standard pancreaticoduodenectomy. These data suggest that venous involvement is a function of tumour location rather than an indicator of aggressive tumour biology.

Adult↗

PubMed1998

Unknown primary cancer presenting as an adrenal mass: frequency and implications for diagnostic evaluation of adrenal incidentalomas.

BACKGROUND: Fine-needle aspiration biopsy to identify adrenal metastasis from an occult primary malignancy has been recommended as part of the evaluation of the patient who presents with an incidentally discovered adrenal mass. This recommendation was assessed by examining the frequency of adrenal involvement in patients with suspected unknown primary cancer. METHODS: Data from 1715 patients referred for evaluation of suspected unknown primary cancer were retrospectively reviewed. RESULTS: Of 1639 patients found to have cancer, the adrenal gland was identified as a site of involvement at presentation in 95 (5.8%). Involvement was limited to the adrenal gland in 4 patients (0.2%). All 4 patients had large (> or = 6 cm) adrenal tumors, 3 of 4 had bilateral involvement, and all had symptoms that otherwise mandated evaluation for an occult malignancy; none had a true adrenal incidentaloma. CONCLUSIONS: Although cancer of an unknown primary site occasionally involves the adrenal gland, metastatic cancer presenting as a true adrenal incidentaloma is extremely rare. Therefore, in the absence of a history of prior malignancy or symptoms, physical examination findings, radiographic findings, or laboratory findings suggestive of an occult malignancy, we do not recommend fine-needle aspiration biopsy as part of the diagnostic evaluation of the patient who presents with a unilateral adrenal mass.

Adrenal Gland Neoplasms↗

PubMed1998

Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma.

PURPOSE: To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with radiographically resectable localized adenocarcinoma of the pancreatic head were entered onto a preoperative protocol that consisted of a 2-week course of fluorouracil (5-FU) 300 mg/m2 daily 5 days per week and concomitant rapid-fractionation radiation 30 Gy, 3 Gy daily 5 days per week. Radiographic restaging was performed 4 weeks after chemoradiation, and patients with localized disease underwent pancreaticoduodenectomy with EB-IORT 10 to 15 Gy. RESULTS: Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. CONCLUSION: Combined modality treatment with preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and EB-IORT is associated with minimal toxicity and excellent locoregional control. This represents one approach to maximize the proportion of patients who receive all components of combined modality therapy and avoids the toxicity of pancreaticoduodenectomy in patients found to have metastatic disease at the time of restaging.

Adenocarcinoma↗