Biomedical subjects

David W Ollila

Publications and source records attributed to David W Ollila.

At least 19 recordsLinked to original sources

PubMed2007

Feasibility of breast preserving therapy with single fraction in situ radiotherapy delivered intraoperatively.

BACKGROUND: Accelerated partial breast irradiation (APBI) has gained widespread interest as a means of improving the convenience and availability of breast conserving radiotherapy. Intraoperative radiation therapy (IORT) is an APBI technique that delivers breast radiotherapy as a single dose at the time of partial mastectomy. We adapted the technique of Veronesi to deliver IORT prior to tumor excision to improve delivery to the region at risk and reduce the volume of normal tissue irradiated. METHODS: Patients age >or=55 with ultrasonographically defined tumors <or=3 cm and invasive ductal carcinoma confirmed by core biopsy were eligible. Pre-operative ultrasound was performed at the time of needle localization and radiocolloid injection. IORT treatment planning was performed prior to surgery using ultrasound tumor definition, selecting cone size and electron energy to optimize dose distribution. In the operating room, the surgeon retracted the skin over the tumor, cone was placed and radiotherapy delivered. Standard partial mastectomy was then performed. RESULTS: Twenty-three patients were enrolled in the study. Eighteen patients completed IORT with 10 patients having successful IORT no additional local therapy necessary. In five patients, the intraoperative radiation therapy served as the boost and in three patients unsuspected larger tumors or multicentric disease necessitated a mastectomy. The majority of patients had a good to excellent cosmetic result. CONCLUSIONS: Single fraction in situ IORT prior to partial mastectomy is feasible for patients with small breast cancers in achieving a good to excellent cosmetic result. Based on this early preliminary data, we plan to expand our feasibility trial.

Aged↗

PubMed2006

Sentinel lymph node biopsy during pregnancy: initial clinical experience.

The diagnosis of breast cancer or melanoma in a pregnant patient presents some unique and difficult challenges for both patients and providers. Lymphatic mapping and sentinel lymph node (SLN) biopsy has become an attractive alternative to elective lymphadenectomy procedures for patients with breast cancer and melanoma. However, there is no data on the safety or utility of sentinel node mapping in pregnant patients. Therefore, we reviewed our experience with mapping in gravid patients. Academic institutions throughout North Carolina were asked to contribute cases of mapping performed during pregnancy. A total of nine women underwent sentinel node mapping during pregnancy. All nine were Caucasian with an average age of 32. SLN were found in all cases and mapping procedures were for breast cancer (three), and melanoma (six). There were no adverse reactions to the SLN procedures and one patient developed a seroma at a biopsy site. All went on to have term deliveries without known adverse effects. This limited experience shows that SLN mapping procedures are feasible in pregnant patients. However, this is not a general endorsement of such procedures in pregnant patients. We suggest that potential risks of vital dye or radioactive tracers be clearly explained to the parents when the mother is a candidate for a mapping procedure, and be balanced against the risk of delaying therapy or omitting nodal staging.

Adult↗

PubMed2006

Size of residual lymph node metastasis after neoadjuvant chemotherapy in locally advanced breast cancer patients is prognostic.

BACKGROUND: The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome. METHODS: Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS). RESULTS: In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively). CONCLUSIONS: Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.

Adult↗

PubMed2006

Population-based analysis of lymphatic mapping and sentinel lymphadenectomy utilization for intermediate thickness melanoma.

BACKGROUND AND OBJECTIVES: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) is the nodal staging procedure of choice for patients with intermediate thickness melanoma. We hypothesize that a significant portion of these patients are not undergoing LM/SL. We explore factors that influence use of LM/SL. METHODS: Analysis was performed of all incident cases of invasive cutaneous melanoma in North Carolina between January 1, 1999 and December 31, 2001. RESULTS: Three thousand four hundred and thirty-six cases of melanoma were reported for 1999-2001. Two hundred and seventy-three cases (8%) were excluded due to metastases. Nine hundred and sixteen cases (29%) were excluded because the T classification was not reported. Of the remaining cases, 1,242 (55%) were intermediate thickness (T2-3); 48% (596/1,242) underwent LM/SL. Subjects >or=60 years old were less likely to receive LM/SL than subjects <60 years (39% vs. 55.4%, P < 0.001). Subjects with head/neck primary tumors were less likely to receive LM/SL than other subjects (33% vs. 51%, P < 0.001). Subjects with T3 tumors were more likely to receive LM/SL than those with T2 tumors (54% vs. 42%, P < 0.001). CONCLUSIONS: Half of all patients with intermediate thickness melanoma in North Carolina do not receive LM/SL. Use of LM/SL varies by patient age and primary tumor site. Further investigation is warranted to explore these differences.

Adult↗

PubMed2006

Axillary lymph node count is lower after neoadjuvant chemotherapy.

BACKGROUND: Retrieval of fewer than 10 lymph nodes at axillary dissection (ALND) for breast cancer can represent anatomic variation or inadequate dissection. We postulated that despite aggressive ALND, a lower lymph node count is more frequent after neoadjuvant chemotherapy. METHODS: Patients who received neoadjuvant chemotherapy followed by ALND were compared with patients who received surgery first. All patients received a level I and II ALND at a single institution by one of the breast surgeons. The number of nodes retrieved at ALND was dichotomized into categories (< 10 and > or = 10), and compared using Fisher exact test. RESULTS: A total of 143 neoadjuvant and 170 surgery-first patients were studied. Patients treated with neoadjuvant chemotherapy were significantly more likely to have fewer than 10 lymph nodes retrieved at ALND than were the surgery-first patients (19/143 or 13% vs. 6/170 or 4%, P = .003). CONCLUSIONS: A low lymph node count is more common in patients after treatment with neoadjuvant chemotherapy and should not be assumed to represent an incomplete ALND.

Adult↗

PubMed2006

Successful minimally invasive parathyroidectomy for primary hyperparathyroidism without using intraoperative parathyroid hormone assays.

BACKGROUND: The need for intraoperative parathyroid hormone (iPTH) assays in minimally invasive parathyroidectomy (MIP) remains controversial. We report the results of MIP performed without the use of iPTH assays. METHODS: This was a single-institution retrospective review of patients with primary hyperparathyroidism treated with MIP between October 1, 1998, and December 31, 2002. RESULTS: Seventy-seven patients were studied. The mean preoperative calcium level was 11.4 mg/dL. All patients had a normal calcium level postoperatively (range, 7.4-10.2 mg/dL, mean, 9.1 mg/dL). Three patients (4%) required re-exploration for various reasons including the development of a second adenoma, secondary hyperparathyroidism, and discordant pathology. All 3 patients initially were eucalcemic. CONCLUSIONS: Our success rate of 96% using a combination of preoperative sestamibi scans, intraoperative gamma probe localization, and selective frozen pathology is consistent with the published success rates using iPTH assays of 95% to 100%. We conclude that MIP can be performed successfully without using iPTH assays.

Adolescent↗

PubMed2006

Surgical management of distant metastases.

Although the location of metastases is of prognostic importance in stage IV melanoma, as seen in the revised AJCC staging classification system and other studies, certain guiding principles apply to patients who have any stage IV disease. Close follow-up of any patient who has melanoma may identify surgically resectable metastatic disease, although this method is controversial. Components of this monitoring may include careful questioning to determine symptoms, such as cough, abdominal pain, or headaches; physical examination for evidence of skin, soft tissue, and lymph node metastases; and screening tools, such as radiographs and laboratory tests. Identifying patients who have metastatic disease at the earliest stage possible is crucial for surgical resection to be an option. Patients should also be thoughtfully evaluated for the possibility of a complete surgical re-section. Complete metastectomy, regardless of the anatomic site, confers survival advantages not seen with other treatment modalities. This aggressive surgical approach should be tempered with the knowledge that incomplete resections put patients at increased risk without any proven survival benefit, and should be reserved only for palliation of symptoms. Systemic adjuvant therapies for stage IV melanoma are evolving, but do not yet confer the survival advantage of complete surgical resection. Until novel drug therapies show efficacy and significantly prolong survival in patients who have stage IV disease, careful consideration should be given to a complete metastectomy if technically feasible.

Brain Neoplasms↗

PubMed2006

Complete metastasectomy in patients with stage IV metastatic melanoma.

Patients with stage IV melanoma have traditionally been managed with various systemic treatments; however, overall survival with this approach has been disappointing. Findings of many retrospective, single-institution, and multicentre studies suggest that participants treated with complete metastasectomy for stage IV metastases have enhanced overall 5-year survival. Complete surgical resection of metastatic disease to stage IV sites-including skin, soft tissue, distant lymph nodes, lungs, or other non-CNS visceral regions-offers the best chance for prolonged survival. This Review will present data lending support to the idea that if complete surgical metastasectomy is technically feasible, then surgery should be the first option for properly selected patients with stage IV melanoma.

Humans↗

PubMed2006

Experienced radio-guided surgery teams can successfully perform minimally invasive radio-guided parathyroidectomy without intraoperative parathyroid hormone assays.

Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays.

Adenoma↗

PubMed2005

American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome.

BACKGROUND: Response to neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Most breast cancer response classification systems use pathologic complete response, either alone or in conjunction with clinical assessments, to categorize response. We examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast to predict patient survival after neoadjuvant chemotherapy for breast cancer. METHODS: We assessed the pathologic stage of residual tumor in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy and examined the association between AJCC TNM stage and subsequent distant disease-free survival and overall survival. All statistical tests were two-sided. RESULTS: At a median follow-up of 5 years, pathologic stage in the surgical specimens after neoadjuvant chemotherapy using the revised AJCC system was strongly associated with both distant disease-free survival and overall survival. A higher pathologic stage of residual tumor after neoadjuvant chemotherapy was associated with a statistically significant lower rate of distant disease-free survival (stage 0: 95%, stage I: 84%, stage II: 72%, and stage III: 47%; Ptrend < .001). The 5-year distant disease-free survival for patients with residual stage IIIC tumors was only 18% (95% CI = 0% to 36%). CONCLUSION: Classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival.

Adult↗

PubMed2005

Cutaneous melanoma: update on prevention, screening, diagnosis, and treatment.

Melanoma is an increasingly common malignancy, and it affects a younger population than most cancers. Risk factors for melanoma include white race, sun sensitivity, family history of melanoma, and melanocytic nevi. Sunburn and intermittent sun exposure appear to increase the risk of developing melanoma. The role of population-based screening for skin cancer remains unclear. Consistent screening results in the diagnosis of thinner melanomas, but there is no evidence that this leads to decreased mortality. The ABCDs--asymmetry, border, color, diameter--can be used as a guide to differentiate melanoma from benign lesions. Suspicious pigmented lesions should undergo full thickness biopsy. Treatment consists of surgical resection, lymph node evaluation, and systemic therapy for some patients. Prognosis depends on the stage at diagnosis. Patients with melanoma require dose follow-up because they are at risk for recurrence and diagnosis of a second primary tumor. Preventive strategies for melanoma should emphasize seeking shade when outdoors, wearing protective clothing, and avoiding exposure during the peak sunlight hours.

Female↗

PubMed2005

Lymphatic mapping and sentinel lymphadenectomy prior to neoadjuvant chemotherapy in patients with large breast cancers.

BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) accurately evaluates the axilla in patients with small breast cancers. LM/SL in patients with large breast cancers is controversial. We examined the accuracy of LM/SL prior to neoadjuvant chemotherapy in patients with large (>3.5 cm) breast cancers. METHODS: Patients with large breast cancers underwent LM/SL prior to neoadjuvant chemotherapy using 99m-technetium radiocolloid and isosulfan-blue dye technique. RESULTS: Twenty-one patients with large (median 5.0 cm) breast cancers underwent LM/SL prior to neoadjuvant chemotherapy. Twelve patients had a tumor-free sentinel node (SN) and received doxorubicin-based chemotherapy; 9 patients had disease in the SN and received doxorubicin followed by a taxane. No patient progressed while receiving neoadjuvant chemotherapy, nor has there been an axillary recurrence (median 36 months). CONCLUSIONS: LM/SL performed prior to neoadjuvant chemotherapy in patients with large breast cancers is an accurate method of axillary staging. Axillary staging prior to neoadjuvant chemotherapy may have prognostic and therapeutic implications.

Adult↗

PubMed2005

Staged sentinel lymph node biopsy before mastectomy facilitates surgical planning for breast cancer patients.

BACKGROUND: In patients with breast cancer who choose mastectomy with immediate reconstruction, the sentinel lymph node (SLN) status on permanent histology may complicate treatment if a metastasis is found. The purpose of this study was to determine how performing an SLN biopsy (SLNB) before the definitive operation would influence subsequent surgical procedures. METHODS: Our SLN database was searched for patients who underwent staged SLNB with subsequent mastectomy between 2001 and 2004. RESULTS: Twenty-five patients with 27 breast cancers underwent SLNB before mastectomy. Of them, 9 of 27 (33%) were node positive. All 9 patients underwent modified radical mastectomy. Three node-positive patients did not undergo immediate reconstruction. Of the remaining 6 node-positive patients, 5 underwent reconstruction with autologous tissue rather than a tissue expander. In contrast, 6 of 16 (37%) node-negative patients underwent reconstruction with a tissue expander. CONCLUSIONS: Staged SLNB assists in selecting the appropriate operation in patients who are considering immediate reconstruction.

Adult↗

PubMed2004

Indications for lymphatic mapping and sentinel lymphadenectomy in patients with thin melanoma (Breslow thickness < or =1.0 mm).

BACKGROUND: Patients with thin (Breslow thickness < or =1.0 mm) melanoma have a good prognosis (5-year survival >90%). Consequently, the added benefit of lymphatic mapping and sentinel lymphadenectomy (LM/SL) in these patients is controversial. We hypothesize that LM/SL with a focused examination of the sentinel node (SN) will detect a significant number of SN metastases in patients with thin melanoma and that certain clinical or histopathologic factors may serve as predictors of SN tumor involvement. METHODS: Over 6 years, 349 patients with melanoma underwent LM/SL and were prospectively entered into an institutional review board (IRB)-approved database. LM/SL was performed with a combined radiotracer and blue dye technique. SNs were serially sectioned, and each section was examined by a dermatopathologist at multiple levels with hematoxylin and eosin as well as immunohistochemical stains. RESULTS: One hundred forty-six patients (42%) had a melanoma with Breslow thickness < or =1.0 mm; six (4%) of these 146 patients had a tumor-involved SN. On multivariate analysis, none of the clinical or histopathologic factors examined were significantly associated with SN tumor involvement in patients with thin melanoma. Completion lymphadenectomy was performed on all patients with a tumor-involved SN. None of the patients had non-SN tumor involvement. CONCLUSIONS: The incidence of SN tumor involvement in patients with thin melanoma is considerable. Although we were unable to identify predictors of SN tumor involvement in patients with thin melanoma, efforts to identify predictors of SN tumor involvement should continue. Until better predictors are identified, we continue to advocate offering LM/SL to patients with thin melanomas who demonstrate clinical or histopathologic characteristics that have historically been associated with an increased risk of recurrence and mortality.

Adult↗

PubMed2004

High-resolution axillary ultrasound is a poor prognostic test for determining pathologic lymph node status in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound in detecting axillary lymph node metastases after neoadjuvant chemotherapy in patients with locally advanced breast cancer. METHODS: Fifty-three patients with stage II or III breast cancer undergoing neoadjuvant chemotherapy who had a physical examination, high-resolution axillary ultrasound, and axillary lymph node dissection from January 1999 to September 2003 were included in this study. RESULTS: The positive predictive value of the postchemotherapy ultrasound for predicting pathologic nodal involvement was 83%, but the negative predictive value was only 52%. Postchemotherapy physical examination was also poor at predicting pathologic nodal involvement with a positive predictive value of 93% and a negative predictive value of only 58%. CONCLUSIONS: A negative post-neoadjuvant chemotherapy high-resolution axillary ultrasound or physical examination does not predict pathologic node status, and this test has limited value in this setting.

Adult↗

PubMed2004

Tandem BRAF mutations in primary invasive melanomas.

The RAS/RAF/MAPK pathway likely mediates critical cell proliferation and survival signals in melanoma. BRAF mutations have been found in a high percentage of melanoma cell lines and metastases; however, only a few studies with a limited number of specimens have focused on primary melanomas. We examined BRAF exon 15 mutational status in 37 primary invasive melanomas of varying thicknesses, which had undergone a standardized pathology review. BRAF mutational status was determined using direct manual sequencing of PCR products, followed by resequencing separately amplified DNA aliquots to confirm each mutation. BRAF exon 15 mutations were found in 17 of 37 (46%) primary melanomas. Tumor-specific tandem mutations, encoding either V599K, V599R, or V599E, were found in 5 of 17 (29%) melanomas with BRAF exon 15 mutations. Cloning of BRAF double base-pair substitutions confirmed that both base changes were on the same allele and can result in a positive charge at codon 599. BRAF mutations, including tandem mutations, were frequently found in both thin and thick primary melanomas, implying that these mutations can occur early in the progression of melanoma. The finding of tandem mutations in thin melanomas makes it more likely that they arise as a simultaneous rather than sequential event.

Adult↗

PubMed2003

Phase I pilot clinical trial of human IgM monoclonal antibody to ganglioside GM3 in patients with metastatic melanoma.

PURPOSE: A human monoclonal antibody (L612 HuMAb) that binds to ganglioside GM3 has been developed in our laboratory. L612 HuMAb is a 100% human IgM protein. L612 HuMAb binds to cell surface of melanoma and can kill the cells in the presence of complement. The primary objective of this study was to test the toxicity and pharmacokinetics associated with administration of L612 HuMAb to melanoma patients whose tumor cells expressed GM3. EXPERIMENTAL DESIGN: Nine patients with measurable metastatic melanoma (American Joint Committee on Cancer stage IV) were entered in the study. Eight had failed previous treatments that included chemotherapy, radiation therapy, melanoma cell vaccine, and/or biological therapy. All patients received a 48-h continuous infusion of L612 HuMAb at a dose of 960 mg, 1,440 mg, or 1,920 mg. Five of these patients received a second infusion and one patient received a third infusion, all with the previous dose. RESULTS: Toxicity was limited to transient and mild pruritus and skin rash. One patient complained of pain at the site of subcutaneous metastases. Serum antibody levels peaked 24 to 48 h after starting the infusion. Two patients, one receiving a single course of 960 mg (612 mg/m(2)) and the second receiving two courses of 1,440 mg (911 mg/m(2)) followed by surgical therapy, are without evidence of disease >5 years after antibody infusion. CONCLUSIONS: The human IgM monoclonal antibody, L612 HuMAb, was well tolerated. Infusion of L612 HuMAb appears to produce significant antitumor activity in melanoma patients.

Adult↗

PubMed2003

Extracapsular extension of the sentinel lymph node metastasis: a predictor of nonsentinel node tumor burden.

OBJECTIVE: To identify predictors of nonsentinel node (NSN) tumor involvement in patients with a tumor-involved sentinel node (SN). SUMMARY BACKGROUND DATA: For many breast cancer patients who undergo intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL), the SN is the only tumor-involved axillary node. Associations between NSN tumor involvement and several clinical and histopathologic factors have been identified. The authors hypothesize that extracapsular extension (ECE) of the SN metastasis is highly predictive of NSN tumor involvement. METHODS: Between May 1998 and December 2001, 260 patients (263 cases) with clinical T1 or T2 (<5.0 cm) breast cancer underwent LM/SL at the University of North Carolina, using a combined blue dye and technetium sulfur colloid technique. In all cases with a tumor-involved SN, axillary lymph node dissection (ALND) was recommended. Statistical analysis, with Pearson chi-square tests, Fisher exact test, and multiple logistic regression, was performed. RESULTS: The SN contained tumor in 74 (28.1%) cases. ALND was performed in 70 of the 74 cases. ECE of the SN metastasis was present in 18 (25.7%) of the 70 cases. Patients with ECE of the SN metastasis were more likely to have NSN tumor involvement and had a greater total number of tumor-involved nodes than patients without ECE of the SN metastasis. Increasing size of the SN metastasis and increasing size of the primary tumor, examined as continuous variables, were associated with an increased likelihood of NSN tumor involvement on univariate analysis. However, only ECE of the SN metastasis was associated with NSN tumor involvement on multivariate analysis. CONCLUSIONS: ECE of the SN metastasis is a strong predictor of NSN tumor involvement. All patients with ECE of the SN metastasis should undergo mandatory completion ALND.

Adult↗