Biomedical subjects

Kelly K Hunt

Publications and source records attributed to Kelly K Hunt.

At least 109 records · Page 6Linked to original sources

PubMed2004

Sentinel lymph node biopsy following neoadjuvant chemotherapy: review of the literature and recommendations for use in patient management.

Breast cancer is a significant health problem worldwide and is one of the leading causes of cancer-related mortality in women. Preoperative chemotherapy has become the standard of care for patients with locally advanced disease and is being used more frequently in patients with early-stage breast cancer. Sentinel lymph node biopsy has shown great promise in the surgical management of breast cancer patients, but its use following preoperative chemotherapy is yet to be determined. Eleven studies have been published with respect to the accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed favourable results, with the ability to identify a sentinel lymph node in 84% to 98% of cases, and reported false negative rates ranging from 0% to 20%. The accuracy of sentinel lymph node biopsy following preoperative chemotherapy for breast cancer ranges from 88% to 100%, with higher rates when specific techniques and inclusion criteria are applied. The published literature supports the use of sentinel lymph node biopsy for assessment of the axilla in patients with clinically node-negative disease following preoperative chemotherapy.

Antineoplastic Agents↗

PubMed2004

Delayed-immediate breast reconstruction.

In patients with early-stage breast cancer who are scheduled to undergo mastectomy and desire breast reconstruction, the optimal timing of reconstruction depends on whether postmastectomy radiation therapy will be needed. Immediate reconstruction offers the best aesthetic outcomes if postmastectomy radiation therapy is not needed, but if postmastectomy radiation therapy is required, delayed reconstruction is preferable to avoid potential aesthetic and radiation-delivery problems. Unfortunately, the need for postmastectomy radiation therapy cannot be reliably determined until review of the permanent tissue sections. The authors recently implemented a two-stage approach, delayed-immediate breast reconstruction, to optimize reconstruction in patients at risk for requiring postmastectomy radiation therapy when the need for postmastectomy radiation therapy is not known at the time of mastectomy. Stage 1 consists of skin-sparing mastectomy with insertion of a completely filled textured saline tissue expander. After review of permanent sections, patients who did not require post-mastectomy radiation therapy underwent immediate reconstruction (stage 2) and patients who required postmastectomy radiation therapy completed postmastectomy radiation therapy and then underwent standard delayed reconstruction. In this study, the feasibility and outcomes of this approach were reviewed. Fourteen patients were treated with delayed-immediate reconstruction between May of 2002 and June of 2003. Twelve patients had unilateral reconstruction and two patients had bilateral reconstruction, for a total of 16 treated breasts. All patients completed stage 1. Tissue expanders were inserted subpectorally in 15 breasts and subcutaneously in one breast. The mean intraoperative expander fill volume was 475 cc (range, 250 to 750 cc). Three patients required postmastectomy radiation therapy and underwent delayed reconstruction. Eleven patients did not require postmastectomy radiation therapy. Nine patients had 11 breast reconstructions (stage 2), six with free transverse rectus abdominis musculocutaneous (TRAM) flaps, one with a superior gluteal artery perforator flap, and four with a latissimus dorsi flap plus an implant. The median interval between stages was 13 days (range, 11 to 22 days). Two patients who did not require postmastectomy radiation therapy have not yet had stage 2 reconstruction, one because she wished to delay reconstruction and the other because she required additional tissue expansion before permanent implant placement. Six complications occurred. The stage 1 complications involved two cases of mastectomy skin necrosis in patients who required post-mastectomy radiation therapy; one patient required removal of the subcutaneously placed expander before postmastectomy radiation therapy and the other patient had a subpectorally placed expander that only required local wound care. The stage 2 complications were a recipient-site seroma in a patient with a latissimus dorsi flap, a recipient-site hematoma in the patient with the superior gluteal artery perforator flap, and two arterial thromboses in patients with TRAM flaps. Both TRAM flaps were salvaged. Delayed-immediate reconstruction is technically feasible and safe in patients with early-stage breast cancer who may require postmastectomy radiation therapy. With this approach, patients who do not require postmastectomy radiation therapy can achieve aesthetic outcomes essentially the same as those with immediate reconstruction, and patients who require postmastectomy radiation therapy can avoid the aesthetic and radiation-delivery problems that can occur after an immediate breast reconstruction.

Adult↗

PubMed2004

Platelet kinetics and decreased transfusion requirements after splenectomy for hematologic malignancy.

OBJECTIVE: Thrombocytopenia is a significant and morbid problem in patients with hematologic malignancy, resulting in frequent platelet transfusions and significant resource consumption. We undertook this study to determine the impact of splenectomy on transfusion requirements in patients with chronic leukemia, acute leukemia, myelodysplastic syndrome, and lymphoma. METHODS: Records of 134 patients with hematologic malignancies who underwent splenectomy were reviewed. Results are reported as mean +/- standard error of the mean. RESULTS: Mean preoperative (preop) platelet count was 97 +/- 8 K/microL. A significant rise in platelets, compared with preop, was observed starting on postsplenectomy day 1 (141 +/- 8 K/microL, P < 0.001 versus preop) and persisted through day 7. Counts remained significantly elevated at 3 and 6 months and years 1-5. In profoundly thrombocytopenic patients (preop levels < 20 K/microL), preop count was 11 +/- 1 K/microL. A significant postsplenectomy platelet rise persisted for at least 1 year (137 +/- 52 K/microL, P < 0.05 versus preop). An increased platelet level was observed in all hematologic subgroups; in the chronic leukemias (n = 58, P < 0.01) and in lymphoma (n = 59, P < 0.001), this reached significance. Mean platelet transfusions were significantly decreased from preop (3 months preop: 8.6 +/- 2 units) compared with postsplenectomy (3 months postsplenectomy: 5.0 +/- 1 unit, P = 0.03). This decrease was even more pronounced in profoundly thrombocytopenic patients (31.6 +/- 10.6 units preop versus 8.9 +/- 4.8 units postoperative, P = 0.01). CONCLUSIONS: In the hematologic malignancies, splenectomy produces a significant and longlasting restoration of platelet levels and a resultant decrease in platelet transfusion requirements. These beneficial effects of splenectomy hold true even for the most profoundly thrombocytopenic patients.

Adolescent↗

PubMed2004

Needle localization for excisional biopsy of breast lesions: comparison of effect of use of full-field digital versus screen-film mammographic guidance on procedure time.

The time required to perform needle localization with full-field digital (FFD) mammography was compared with the time required to perform it with screen-film (SF) mammography in 158 women with breast lesions. The time needed to position the patient before the first image was acquired, needle placement time, and total procedure time were compared between techniques. Regression modeling was performed to assess the effect of mammographic guidance method while simultaneously adjusting for other significant covariates. By using the backward selection technique, statistically nonsignificant variables were removed one at a time to produce a final model for which all statistically significant effects were defined as those with P <.10. Total procedure time for all lesions was shorter with FFD than with SF mammography. The time needed to position the patient and needle placement time were also significantly shorter with FFD than with SF mammography. Procedure time for needle localization of breast lesions is significantly shorter with FFD than with SF mammographic guidance.

Adult↗

PubMed2004

Genetically targeted cancer therapy: tumor destruction by PKR activation.

The is a double-stranded RNA-activated protein kinase (PKR) has been largely investigated for its key role in viral host defense. Although best characterized by its function in mediating the antiviral and antiproliferative effects of interferon (IFN), PKR is also implicated in transcriptional regulation, cell differentiation, signal transduction, and tumor suppression. However, recent findings identifying PKR as an important effector of apoptosis have led to an increased interest in PKR modulation as an antitumor strategy. PKR can either be up-regulated through direct induction by the transcription factor E2F-1, or it can be activated through direct protein-protein interactions with the melanoma differentiation-associated gene-7 (MDA7, IL-24). Additionally, the intracellular formation of double-stranded RNA by transfection with antisense RNA complementary to tumor-specific RNA sequences can induce PKR activation and apoptosis selective to these tumor cells. The growing application of viral vector-based gene therapies and oncolytic, replicating viruses that must elude viral defense in order to be effective, has also drawn attention to PKR. Oncolytic viruses, like the attenuated herpes simplex virus R3616, the vesicular stomatitis virus, or reovirus, specifically replicate in tumor cells only because the viral host defense in the permissive cells is suppressed. In this article we review the role of PKR as an effector of apoptosis and a target for tumor treatment strategies and discuss the potential of PKR-modifying agents to treat patients with cancer. Targeted gene therapy against cancer can be approached by activation of PKR with the down-regulation of protein synthesis and induction of apoptosis, or by suppression of PKR with the propagation of oncolytic virus. Since the PKR pathway can be modified by many routes, antitumor therapies combining oncolytic virus, gene therapies, and chemotherapy with PKR modifiers are likely to emerge in the near future as therapeutic options in the treatment of patients with cancer.

Animals↗

PubMed2003

Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: Implications for breast cancer patients with early-stage disease and predictors for recurrence after postmastectomy radiation.

PURPOSE: To compare rates of locoregional recurrence (LRR) after mastectomy, doxorubicin-based chemotherapy, and radiation with those of patients receiving mastectomy and doxorubicin-based chemotherapy without radiation and to determine predictors of LRR after postmastectomy radiation. METHODS: Kaplan-Meier freedom-from-LRR rates were calculated for 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five single-institution clinical trials. The LRR rates in these patients were compared to previously reported rates in 1031 patients treated without radiation in the same trials. RESULTS: Median follow-up was 14 years. Irradiated patients had significantly less favorable prognostic factors for LRR than did unirradiated patients. Despite this, in all subsets of node-positive patients, postmastectomy radiation led to lower rates of LRR. This included patients with T1 or T2 tumors and one to three positive nodes (10-year LRR rates of 3% vs. 13%, p = 0.003). Multivariate analysis of LRR for patients with this stage of disease revealed that no radiation, close/positive margins, gross extracapsular extension, and dissection of <10 nodes predicted for increased LRR (hazard ratios 6.25, 4.61, 3.27, and 2.66, respectively). Significant predictors of LRR for patients treated with postmastectomy radiation were higher number and >or=20% positive nodes, larger tumor size, lymphovascular space invasion, and estrogen receptor (ER)-negative disease. Recursive partitioning analysis revealed ER-negative status to be the most powerful discriminator of LRR in irradiated patients. CONCLUSIONS: Postmastectomy radiation decreases LRR for patients with breast cancer, including those with Stage II breast cancer and one to three positive lymph nodes.

Adult↗

PubMed2003

Neoadjuvant chemotherapy for breast carcinoma: multidisciplinary considerations of benefits and risks.

BACKGROUND: The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. METHODS: The authors reviewed published studies on the effect of neoadjuvant chemotherapy for breast carcinoma on the practice of medical oncology, surgical oncology, radiation oncology, pathology, and radiology. RESULTS: Treating breast carcinoma with neoadjuvant chemotherapy has several advantages, such as providing the earliest possible treatment against preexisting micrometastases, offering selected patients breast conservation therapy, and allowing for measurement of disease response, which can then be used to customize subsequent chemotherapy. However, neoadjuvant chemotherapy affects the practice not only of medical oncology, but also has important implications for the specialties of surgery, radiology, pathology, and radiation oncology. The current review addressed the new opportunities and challenges within the multidisciplinary care of breast carcinoma provided by neoadjuvant chemotherapy. CONCLUSIONS: The complexity of the issues led the authors to conclude that patients who receive neoadjuvant chemotherapy are likely to benefit from a coordinated multidisciplinary approach to their care.

Breast Neoplasms↗

PubMed2003

Outcome of treatment for breast cancer patients with chest wall recurrence according to initial stage: implications for post-mastectomy radiation therapy.

PURPOSE: The impact of postmastectomy radiation therapy (PMRT) on overall survival (OS) for patients with Stage II breast cancer with 1-3 positive lymph nodes is controversial. We sought to compare the outcome of salvage treatment for patients with chest wall recurrence (CWR) according to initial disease stage to shed light on the potential benefit of PMRT in specific subgroups of patients. METHODS: We retrospectively reviewed information concerning 96 patients with CWR who were not previously treated with PMRT. The patients were divided according to their initial extent of disease: T1-T2N0 (Group 1), T1-T2 with 1-3 positive lymph nodes (Group 2), and T3-T4 or > or =4 positive lymph nodes (Group 3). The OS and distant metastasis-free survival (DMFS) from the time of CWR were compared using the method of Kaplan and Meier, and a Cox regression model was used for a multivariate analysis. RESULTS: Group 1 had an improved OS and DMFS compared with Group 2 and Group 3 (p < 0.001), but there were no differences in OS or DMFS between Group 2 and Group 3 (p = 0.250 and p = 0.492, respectively). The respective 5-year rates for the three groups were as follows: OS 79.9% vs. 41.9% vs. 29.1%; DMFS 75.2% vs. 33.6% vs. 25.9%. CONCLUSIONS: Breast cancer patients with T1-T2N0 breast cancer who develop a CWR have a significantly better outcome than those with lymph node-positive disease. Patients with T1-T2 tumors and one to three positive lymph nodes have a similar outcome after CWR as those with larger tumors or more than four positive lymph nodes. These data should be considered when weighing the risks and benefits of PMRT for patients with Stage II breast cancer with one to three positive lymph nodes.

Breast Neoplasms↗

PubMed2003

Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival.

PURPOSE: To evaluate how implementation of the 2003 American Joint Committee on Cancer (AJCC) staging system will affect stage-specific survival of breast cancer patients. PATIENTS AND METHODS: Records of 1,350 patients treated on sequential institutional protocols with mastectomy and adjuvant doxorubicin-based chemotherapy were reviewed. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging criteria. Overall stage-specific survival (OS) was calculated using the Kaplan-Meier method, and hypothetical differences were compared by the log-rank test. RESULTS: Six hundred five of 1,087 patients with stage II disease according to the 1988 classification system had stage II disease according to the 2003 system. The 10-year OS for patients with stage II disease was significantly improved using the 2003 system (76% [2003] v 65% [1988]; P <.0001). Two hundred eighty-nine of 633 patients with stage IIb disease using the 1988 system were stage IIb with the 2003 system, and 10-year OS was 58% (1988) versus 70% (2003; P =.003). The number of patients with stage III disease increased from 207 (1988) to 443 (2003), and the 10-year OS changed from 45% (1988) to 50% (2003; P =.077). Most of this difference resulted from changes within stage IIIa: OS, 45% (1988) versus 59% (2003; P <.0001). CONCLUSION: Stage reclassification using the new AJCC staging system for breast cancer will result in significant changes in reported outcome by stage. It is imperative that careful attention is devoted to this effect so that accurate conclusions regarding the efficacy of new treatment strategies can be drawn.

Breast Neoplasms↗

PubMed2003

Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma.

PURPOSE: The primary objective of this phase I trial was to define the maximum-tolerated dose of external-beam radiation with concurrent fixed-dose continuous-infusion doxorubicin followed by surgical resection and electron-beam intraoperative radiation therapy (EB-IORT) for patients with localized, potentially resectable retroperitoneal sarcomas (RPS). PATIENTS AND METHODS: Thirty-five patients with radiographically resectable primary or recurrent intermediate- or high-grade RPS were treated. Doxorubicin was administered each week for 4 or 5 weeks as an initial bolus (4 mg/m2) followed by a 4-day continuous infusion (4 mg/m2/d). Concurrent radiation therapy was administered in escalating doses of 18.0, 30.6, 36.0, 41.4, 46.8, or 50.4 Gy in 1.8-Gy fractions. Radiographic restaging was performed 4 to 8 weeks after chemoradiation, and patients with localized disease underwent surgical resection with EB-IORT (15 Gy). RESULTS: Chemoradiation was completed as outpatient therapy in 31 patients (89%); four patients required hospital admission during chemoradiation or in the postchemoradiation preoperative period. At the highest radiation dose of 50.4 Gy, two (18%) of 11 patients had grade 3 or 4 nausea. Twenty-nine patients (83%) underwent laparotomy; six patients had interval disease progression and did not undergo surgery. Grossly complete resection (R0 or R1) was performed in 26 (90%) of 29 patients who had surgery. EB-IORT was feasible and successfully administered to 22 patients who had R0 or R1 resections. CONCLUSION: Preoperative chemoradiation, surgical resection, and EB-IORT are feasible for patients with RPS. Preoperative external-beam radiation can be administered to a total dose of 50.4 Gy with continuous-infusion doxorubicin.

Adult↗

PubMed2003

Nipple aspirate fluid cytology in breast carcinoma.

BACKGROUND: Nipple aspirate fluid (NAF) cytology is a simple noninvasive method to study cells exfoliated into the ductal system of the breast. In the current study, the significance of cytologic findings in NAF was determined by correlating them with histopathologic findings from corresponding breast tissue. Cytologic-histologic correlations of NAF were performed in only a few studies. METHODS: Nipple aspirate fluid was collected by breast massaging and by using a breast aspiration device from 74 women with biopsy confirmed intraductal or invasive carcinoma with or without a history of preoperative neoadjuvant chemotherapy. Cytospin preparations were Pap stained. The number of epithelial cells was quantitated and foamy macrophages were semiquantitatively scored. Cytologic findings were categorized as insufficient for diagnosis (less than 10 epithelial cells), benign, mild atypia, marked atypia or suspicious, and malignant. Finally, they were correlated with tissue findings. RESULTS: Nipple aspirate fluid was obtained from 74 women, including 24 who had received preoperative neoadjuvant chemotherapy. The median age of patients was 54 years. A mean volume of 57 microL NAF and a mean of 149 epithelial cells were obtained. Foamy macrophages were present in 51 (70%) of the specimens. There was a significant correlation between the presence of epithelial cells and foamy macrophages (P < 0.001). Patients treated with chemotherapy had fewer epithelial cells in their NAF compared with patients who were not treated with chemotherapy. Thirty specimens (41%) were inadequate for diagnosis, 34 were (46%) benign, 5 (7%) were mildly atypical, 1 (1%) was markedly atypical, and 4 (5%) were malignant. Of the five cases with mildly atypical cytology, three were intraductal papilloma, one was low-grade papillary intraductal carcinoma, and one was low-grade intracystic papillary carcinoma with invasion in the corresponding tissue specimen. The single case with markedly atypical NAF cytology had extensive ductal carcinoma in situ (DCIS). Of the four cases with malignant NAF cytology, two were extensive DCIS and two had invasive carcinoma with extensive DCIS in the breast specimen. Overall, 3 (27%) of 11 cases of DCIS were detected in NAF and only 2 (4%) of 52 invasive carcinomas including the only two cases with extensive DCIS were detected in NAF. CONCLUSION: The probability of detecting malignant cells in NAF is dependent on the extent of DCIS and nipple involvement by DCIS. Nipple aspirate fluid is not a sensitive test for detecting invasive carcinoma of the breast. Atypical cytology in NAF is associated with papillary lesions in the underlying breast.

Adult↗

PubMed2003

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy.

BACKGROUND: The current study identified determinants of systemic recurrence and disease-specific survival (DSS) in patients with early-stage breast carcinoma treated with breast-conserving surgery and radiation therapy (breast-conserving therapy, or BCT). METHODS: The study population consisted of 1,043 consecutive women with Stages I or II breast carcinoma who underwent BCT between 1970 and 1994. Clinical and pathologic characteristics evaluated included age, tumor size, tumor grade, estrogen and progesterone receptor status, surgical margins, axillary lymph node involvement, and use of adjuvant therapy. RESULTS: At a median follow-up time of 8.4 years, 127 patients (12%) had developed an ipsilateral breast tumor recurrence (IBTR), and 184 patients (18%) had developed a systemic recurrence. On multivariate logistic regression analysis, tumor size greater than 2 cm, positive lymph nodes, lack of adjuvant tamoxifen therapy, and positive margins (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.034) were predictors of systemic recurrence. When IBTR was added into the model, adjuvant therapy and surgical margins were not independent predictors; however, IBTR was an independent predictor of systemic recurrence (IBTR vs. no IBTR; OR, 6.2; 95% CI, 3.1-12.3; P < 0.001). The 10 year DSS rate after BCT was 87%. On multivariate Cox proportional hazards model analysis, the following factors were independent predictors of poor DSS: tumor size greater than 2 cm (vs. < or = 2 cm; relative risk [RR], 2.3; 95% CI, 1.2-4.3; P = 0.010), negative progesterone receptor status (vs. positive; RR, 2.7; 95% CI, 1.4-5.1; P = 0.003), positive margins (vs. negative; RR, 3.9; 95% CI, 1.4-11.5; P = 0.011), and IBTR (vs. no IBTR; RR, 5.5; 95% CI, 2.8-11.0; P < 0.001). CONCLUSIONS: Positive surgical margins and IBTR are predictors of systemic recurrence and disease-specific survival after BCT. Aggressive local therapy is necessary to ensure adequate surgical margins and to minimize IBTR.

Breast Neoplasms↗

PubMed2003

Is there a role for surgery in patients with "unresectable" cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?

BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Early reports using Gleevec for the treatment of unresectable GISTs have shown 50% to 60% partial response rates based on radiographic evaluation alone. No study has yet correlated radiographic response with pathologic findings. This retrospective review of patients with cKIT+ GISTs who received Gleevec prior to surgical resection examines the pathologic response to therapy and the feasibility of surgical resection after treatment. METHODS: Patients with cKIT+ GISTs were identified from the institutional sarcoma database. Patients were included if they had pathologic confirmation of cKIT mutation and therapy with Gleevec. The pretreatment and preoperative radiographs, surgeons' operative notes, and pathology reports were reviewed for documentation of the extent of disease. RESULTS: Between January 2001 and Octorber 2002, 126 patients with unresectable cKIT + GISTs treated with Gleevec were identified. Of these 126 patients, 17 have subsequently undergone surgical resection after a median of 10 months (range 2 to 16) of treatment with Gleevec. Based on computed tomographic (CT) scanning, 1 (6%) patient had evidence of a complete tumor response, 12 (70%) patients had a partial response, 3 (24%) patients had stable disease, and 1 (6%) patient had progressive disease. Posttreatment/preoperative CT imaging documented an overall response rate of 76%. The pathologic review of the operative specimens showed that 2 (12%) patients had a complete response to therapy, 11 (65%) had a partial response to therapy, 3 (18%) patients had no evidence of treatment effect on the excised tumor, 1 patient had progressive disease. Sixteen patients (94%) underwent complete surgical resection of disease, including 3 patients with no pathologic evidence of response to therapy. One patient had progression of disease and was unresectable at surgical exploration. CONCLUSIONS: This series is the first to present pathologic data after the treatment of cKIT+ GISTs with Gleevec. In this series, the majority of responses were limited to partial responses, indicating that surgical resection remains a vital component of the treatment plan for patients with cKIT+ GISTs. This series is consistent with previous reports indicating that complete responses are extremely rare in response to treatment with Gleevec. Patients with advanced disease may benefit from a course of neoadjuvant therapy with Gleevec followed by resection, even when there is evidence of multifocal disease. A prospective evaluation of neoadjuvant Gleevec therapy for advanced cKIT+ GISTs is warranted.

Adult↗

PubMed2003

Intraoperative margin assessment reduces reexcision rates in patients with ductal carcinoma in situ treated with breast-conserving surgery.

BACKGROUND: Reported rates of reexcision for margin control after breast-conserving surgery for ductal carcinoma in situ (DCIS) range from 48% to 59%. The optimal technique for intraoperative margin assessment in patients with DCIS has yet to be defined. We sought to determine whether intraoperative multidisciplinary evaluation using gross tissue assessment and sectioned-specimen radiography reduces the need for reoperation for margin control in DCIS. METHODS: A prospectively compiled database was used to identify patients who had DCIS diagnosed by core needle biopsy and were treated with breast-conserving surgery at our institution between July 1999 and July 2002. All patients had intraoperative gross margin assessment and specimen radiography of both the whole and sliced specimen for calcifications. RESULTS: Four hundred two patients with DCIS were evaluated at our institution during the study period. Of these, 160 had excisional biopsy for diagnosis prior to referral, 92 had mastectomy as their initial procedure, 40 were seen for a second opinion only, and 1 patient refused surgery. The remaining 109 patients formed the study population. The median age was 55 years (range 34 to 81). The median pathologic size of DCIS was 1.2 cm (range 0.2 to 8.0 cm). Fifty-nine patients had positive (less than 1 mm) or close (less than 5 mm) margins on intraoperative assessment. Final pathology agreed with intraoperative assessment of a positive or close margin in 43 of the 59 patients (P = 0.00005). Seventy-five percent of those thought to have a positive or close margin at the time of surgery (n = 44) underwent intraoperative reexcision. Of the total 109 patients, 31 (34%) had an intraoperative reexcision that resulted in a change in margin status from positive on intraoperative evaluation to negative on final pathologic evaluation (P < 0.00001). A second procedure for margin control was necessary in only 24 patients (22%). The decision to excise additional tissue at the first surgery on the basis of intraoperative assessment resulted in significantly fewer second procedures for margin control (P = 0.029). CONCLUSIONS: In patients with DCIS, intraoperative margin assessment by gross pathological examination and sliced specimen radiography significantly affects intraoperative decision making, and excision of further tissue on the basis of intraoperative assessment results in a substantial decrease in second procedures for margin control.

Adult↗

PubMed2003

Adenoviral melanoma differentiation-associated gene 7 induces apoptosis in lung cancer cells through mitochondrial permeability transition-independent cytochrome c release.

OBJECTIVE: Melanoma differentiation-associated gene 7 is a novel tumor suppressor gene that induces apoptosis in lung cancer cells when delivered by adenoviral gene transfer as Ad-mda7. The mechanisms of action are not well defined but may involve release of cytochrome c from the mitochondria with subsequent caspase activation. METHODS: The lung cancer cell lines A549 and H1299 were transduced with Ad-mda7, adenovirus containing the gene for p53 (Ad-p53), and control adenoviral luciferase vectors. Staurosporine was used as a positive control to induce cytochrome c release through mitochondrial permeability transition-dependent pores, whereas cyclosporine (INN: ciclosporin) was used to specifically inhibit these mitochondrial permeability transition-dependent pores. Apoptosis was evaluated with fluorescence-activated cell sorting analysis of subdiploid populations and mitochondrial membrane potential changes with tetramethylrhodamine ethylester perchlorate. RESULTS: Melanoma differentiation-associated gene 7, transduced by Ad-mda7 into H1299 and A549 lung cancer cells, resulted in sharp increases in cytosolic cytochrome c levels followed by induction of apoptosis and cellular death. The release of cytochrome c from the mitochondria occurred without changes in the mitochondrial membrane potential. Unlike staurosporine treatment, transduction with Ad-p53 and Ad-mda7 caused releases of cytochrome c and apoptosis that were not blocked by cyclosporine, suggesting a mitochondrial permeability transition pore-independent pathway. CONCLUSIONS: Ad-mda7 induces apoptosis in lung cancer cells through mitochondrial cytochrome c release in a process that is not dependent on mitochondrial membrane potential changes and occurs through mitochondrial permeability transition-independent pores. This unique mechanism of action may allow treatment of patients with lung cancer resistant to mitochondrial permeability transition-dependent cell death processes.

Adenoviridae↗

PubMed2003

Radiation therapy as an adjuvant treatment after sentinel lymph node surgery for breast cancer.

Radiation therapy is an effective treatment of micrometastatic disease involving lymph nodes. Correspondingly, radiation may be an important adjuvant treatment for selected patients who undergo sentinel lymph node surgery. The specific cohorts for whom radiation maybe of benefit include those at risk for a false-negative surgery, patients with a positive sentinel lymph node who elect to forgo an axillary dissection, and patients with drainage to the internal mammary lymph nodes. For these patients, radiation treatment fields must be specifically designed to include the appropriate nodal regions within the target treatment volumes.

Breast Neoplasms↗

PubMed2003

Experimental approaches to treatment of soft tissue sarcoma.

The experimental approaches described in this article represent potential new approaches for targeted therapy. Thus far, none of the preclinical data have demonstrated a cure for sarcomas; however, the antitumor effects of many of these new agents seem to be enhanced when the agents are combined with chemotherapeutic agents. The combination of novel therapeutics with conventional chemotherapy may be the most effective strategy in terms of maximization of tumor killing and minimization of toxicity and the risk of drug resistance. Not only are new drugs being developed for treatment of sarcomas but new ways of delivering drugs are also being investigated. The angiogenic, or metronomic, schedule of drug delivery may be preferable to conventional schedules in achieving optimal tumor inhibition. In addition, isolated limb perfusion is a unique approach to delivery of drugs, such as TNF and melphalan, for sarcomas and melanomas [137, 138]. The advantages of this method of drug delivery include the ability to administer therapeutic agents in high concentrations to a specific region of the body without systemic toxicity. Further advances in the understanding of the biology of sarcomas along with novel approaches to delivery of drugs are crucial to the development of new and effective therapies.

Angiogenesis Inhibitors↗

PubMed2003

Surgical decision making and factors determining a diagnosis of breast carcinoma in women presenting with nipple discharge.

BACKGROUND: There is no consensus about the use of the various diagnostic tests and surgical procedures available to confirm or rule out breast cancer in patients presenting with nipple discharge. This study was designed to identify patient and nipple-discharge characteristics associated with the diagnosis of breast cancer and to determine the utility of mammography, sonography, ductography, and cytology in surgical decision making in patients presenting with pathologic nipple discharge. STUDY DESIGN: We reviewed the medical records of all patients who presented with nipple discharge at our institution between August 1993 and September 2000. Patient and nipple-discharge characteristics and findings on imaging studies and cytologic examination were analyzed. RESULTS: A total of 146 patients presented at our institution with nipple discharge during the study period. Of these, 52 had clinically benign discharge and were managed without surgical intervention; 94 patients had pathologic discharge and underwent a biopsy procedure for histologic diagnosis, treatment, or both. Logistic regression analysis identified mammographic (relative risk [RR] = 10.47, 95% confidence interval [CI] 2.36 to 46.39, p = 0.0002) and sonographic (RR = 5.54, 95% CI 1.27 to 25.40, p = 0.028) abnormalities as independent factors associated with a malignant diagnosis. Nineteen cancers, 62 papillomas, and 13 other benign lesions were identified among the patients with pathologic discharge. In 3 patients with cancer (15.8%) and 30 patients with a papilloma (48.4%), ductography was the only means of identifying lesions to be resected. Patients who underwent ductography-guided operation (n = 42, 50%) or any surgical procedure including a localization study (n = 66, 78.6%) were significantly more likely than patients who underwent central duct excision alone to have a specific underlying lesion identified (p = 0.045 and p = 0.033, respectively). CONCLUSIONS: Abnormalities on mammography and sonography in patients with nipple discharge should alert physicians to the possibility of a breast cancer diagnosis. In patients with pathologic discharge with normal findings on physical examination and other imaging studies, ductography might be the only means of localizing and resecting breast lesions associated with nipple discharge.

Adult↗