The Pivotal Leadership of Doctors R. Lee Clark and Murray M. Copeland in Transforming the Commission on Cancer (1955-1965).

In September 1959, Dr. Clark was appointed as Chair and Dr. Murray M Copeland as Vice Chair of the Committee on Cancer. With their typical leadership style to improve the functions and value of organizations, they reorganized and revitalized the Committee on Cancer during the next 6 years. Thus, Drs. Clark and Copeland and the Committee members developed more uniform standards of cancer registries, implemented the American Joint Committee on Cancer Staging and End Results Reporting (with Dr. Copeland as Chair), published a revised Manual for Cancer Programs (which defined minimum standards requisite for approval of a cancer service), established a new regionalization program (with liaison surgeons from each state), and planned all the cancer educational programs for the College's annual Clinical Congress and Sectional Meetings. Importantly, Clark and Copeland led a 10-year strategic plan (called the "Program of the Sixties") to expand and revitalize the scale and scope of the Committee's activities and to reorganize the Committee structure by including liaison members from other physician, oncologic, and hospital organizations. As Dr. Clark completed his 5-year tenure as Committee Chair in October 1964, he formally recommended a reorganization of the Committee on Cancer to assume an even greater role in the cancer community as the Commission on Cancer. As the new Committee Chair, Dr. Copeland shepherded this recommendation to the ACS Board of Regents, which was approved and implemented in July 1965. The Regents emphasized that the functions and activities of the Committee on Cancer had become so complex and far reaching (under Clark's and Copeland's leadership) that its many subcommittees had already assumed duties of committee stature. Dr. Copeland thus became the first Chair of the Commission on Cancer until October 1965, when Dr. John Cline became Chair. For his contributions to the cancer field and to the College of Surgeons, Dr. Clark received their Distinguished Service Award in October 1969 "for his life-long devotion to the treatment of patients and to research in cancer, for notable service to this College, particularly as Chairman of the Cancer Commission from 1960 to 1964."

Braun enteroenterostomy is associated with reduced delayed gastric emptying and early resumption of oral feeding following pancreaticoduodenectomy.

BACKGROUND AND OBJECTIVES: Morbidity rates following pancreaticoduodenectomy (PD) remain high with delayed gastric emptying (DGE) and slow resumption of oral diet contributing to increased postoperative length of stay. A Braun enteroenterostomy has been shown to decrease bile reflux following gastric resection. We hypothesize that addition of Braun enteroenterostomy during PD would reduce the sequelae of DGE. METHODS: From our PD database, patients were identified that underwent classic PD with partial gastrectomy from 2001 to 2006. All patients with reconstruction utilizing a single loop of jejunum at the University of Florida Shands Hospital were reviewed. Demographics, presenting signs and symptoms, pathologic diagnoses, and postoperative morbidity were compared in those patients undergoing reconstruction with an additional Braun enteroenterostomy (n = 70) to those not undergoing a Braun enteroenterostomy (n = 35). RESULTS: Patients undergoing a Braun had NG tubes removed earlier (Braun: 2 days, no Braun: 3 days, P = 0.002) and no significant change in postoperative vomiting (Braun: 27%, no Braun: 37%, P = 0.37) or NG tube reinsertion rates (Braun: 17%, no Braun: 29%, P = 0.21). Median postoperative day with tolerance of oral liquids (Braun: 5, no Braun: 6, P = 0.01) and solid diets (Braun: 7, no Braun: 9, P = 0.01) were significantly sooner in the Braun group. DGE defined by two criteria including the inability to have oral intake by postoperative day 10 (Braun: 10%, no Braun: 26%, P < 0.05) and the international grading criteria (grades B and C, Braun: 7% vs. no Braun: 31%, P = 0.003) were significantly reduced in those undergoing the Braun procedure. In addition, the median length of stay (Braun: 10 days, no Braun: 12 days, P < 0.05) was significantly reduced in those undergoing the Braun procedure. The rate of pancreatic anastomotic failure was similar in the two groups (Braun: 17% vs. no Braun: 14%, P = 0.79). Median bile reflux was 0% in those undergoing a Braun. CONCLUSIONS: The present study suggests that Braun enteroenterostomy can be safely performed in patients undergoing PD and may reduce the indicence of DGE and its sequelae. Further studies of Braun enteroenterostomy in larger randomized trials of patients undergoing PD are warranted.

Is there an indication for initial conservative management of pancreatic cystic lesions?

BACKGROUND: The management of small pancreatic cystic lesions presents a clinical challenge. METHODS: We reviewed our experience with 78 patients who presented with a cystic pancreatic lesion who underwent operative management between 1995 and 2005. Data on cyst characteristics were analyzed in the context of pathologic findings following resection. RESULTS: Among 78 patients, there were 55 (71%) females; median age 63 years. Patients presented with: an incidental finding (48%), pain (40%), acute pancreatitis (4%), other (8%). Operations were distal pancreatectomy (n = 47), pancreaticoduodenectomy (n = 16), and other (n = 15). Most patients had a non-malignant lesion (n = 65, 83%) (mucinous cystadenoma (n = 29), serous cystadenoma (n = 15), IPMN without invasion (n = 8), pseudocyst (n = 8), other benign (n = 5)). Malignant lesions (adenocarcinoma, neuroendocrine tumor, and other) were found in 13 patients (17%). The risk of malignancy increased with size: <3 cm (n = 25), 4%; 3-5 cm (n = 23), 13%; and >5 cm (n = 30), 30%. Pre-operative cyst fluid cytology was performed in 41 patients. The negative predictive value (NPV) of cytology for malignancy was 88% and the positive predictive value (PPV) was 80%. The NPV of CA 19-9 for malignancy was 90%; the PPV was 50%. CONCLUSIONS: Initial conservative management of small cystic pancreatic lesions may be indicated in selected patients.

Nodular fasciitis: differential considerations and current management strategies.

Nodular fasciitis (NF) typically presents as an enlarging soft tissue mass with imaging characteristics that may be suggestive of soft tissue sarcoma or desmoid tumor. This presentation can make a correct diagnosis and management of patients with NF a challenge. We report our recent experience with two cases of NF that were both referred with a diagnoses of "soft tissue sarcoma." Patient 1 was a 46-year-old woman who had undergone breast augmentation and was referred with a rapidly growing firm mass on the left chest wall beneath the breast implant. Computed tomography of the chest noted the mass to be 8 cm x 11 cm in size displacing the implant laterally with no radiological involvement of the bony structures of the chest. Core biopsy was suggestive of inflammation only. Given the clinical suspicion of malignancy, the patient underwent resection of the mass with implant removal. Final pathology showed NF. Patient 2 was a 65-year-old woman referred with an enlarging tender 3-cm infraclavicular mass and a clinical diagnosis of "soft tissue sarcoma." Preoperative biopsy suggested NF. The patient underwent complete excision, which confirmed the diagnosis. These cases highlight the clinical issues associated with management of patients with NF. Current approaches to evaluation, diagnosis, and treatment of NF are discussed.

Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1.

The role of operation in patients with Multiple Endocrine Neoplasia Type 1 (MEN-1) and Zollinger-Ellison Syndrome (ZES) is controversial. Our institutional bias for this disease has, in general, been towards aggressive imaging and operative removal of localized gastrinomas. Few studies have reported long-term outcomes in patients with MEN-1 and ZES. A single institution retrospective review of all patients with MEN-1 and ZES from 1970 to present was performed. Twelve patients were identified (median age = 37 years at diagnosis). The median follow-up was 18 years from diagnosis of ZES. Common symptoms associated with gastrinoma in these patients were diarrhea (n = 6), abdominal pain (n = 4), and nausea/vomiting (n = 4). Most commonly identified sites of gastrinoma were: pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1). Fifteen celiotomies were performed in total (median = 1; range 0-3). Operative procedures performed included: distal pancreatectomy (n = 4), acid reducing procedure (n = 4), enucleation of pancreatic gastrinoma (n = 3), duodenal resection (n = 3), pancreaticoduodenectomy (n = 1), and other (n = 7). One patient had a transient biochemical cure after operation lasting 3 years. Only one patient in this series had documented liver metastases of gastrinoma and no patients expired of metastatic gastrinoma. There was one postoperative patient death, secondary to respiratory arrest thought to be a result of aspiration or pulmonary embolus. Three patients died of nondisease related causes, and seven patients were alive at the time of last follow-up. Operations rarely result in biochemical cures in patients with MEN-1 and ZES. In our experience, resection of localized gastrinomas often did not require extended surgical resection and were associated with excellent long-term outcomes.

Breast MR for the evaluation of occult nipple discharge.

Pathologic nipple discharge often presents a diagnostic and therapeutic dilemma for clinicians. We present two patients with pathologic nipple discharge in whom breast MR facilitated preoperative identification of and management of otherwise occult index lesions. Breast MR should be considered in the toolbox for evaluation of occult nipple discharge when other available strategies have failed to demonstrate an underlying etiology for the pathologic discharge. The use of breast MR in this setting may permit directed evaluation and management of potentially malignant lesions.

Long-term outcomes in breast cancer patients with ten or more positive axillary nodes treated with combined-modality therapy: the importance of radiation field selection.

PURPOSE: To determine the long-term outcome of a consistent treatment approach with electron beam postmastectomy radiation therapy (PMRT) in breast cancer patients with > or =10 positive nodes treated with combined-modality therapy. METHODS AND MATERIALS: TSixty-three breast cancer patients with > or =10 positive lymph nodes were treated with combined-modality therapy using an electron beam en face technique for PMRT at the University of Florida. Patterns of recurrence were studied for correlation with radiation fields. Potential clinical and treatment variables were tested for possible association with local-regional control (LRC), disease-free survival (DFS), and overall survival (OS). RESULTS: TAt 5, 10, and 15 years, OS rates were 57%, 36%, and 27%, respectively; DFS rates were 46%, 37%, and 34%; and LRC rates were 87%, 87%, and 87%. No clinical or treatment variables were associated with OS or DFS. The use of supplemental axillary radiation (SART) (p = 0.012) and pathologic N stage (p = 0.053) were associated with improved LRC. Patients who received SART had a higher rate of LRC than those who did not. Moderate to severe arm edema developed in 17% of patients receiving SART compared with 7% in patients not treated with SART (p = 0.28). CONCLUSIONS: TA substantial percentage of patients with > or =10 positive lymph nodes survive breast cancer. The 10-year overall survival in these patients was 36%. The addition of SART was associated with better LRC.

Association between operative closure type and acute infection, local recurrence, and disease surveillance in patients undergoing breast conserving therapy for early-stage breast cancer.

BACKGROUND: This study investigates the effect of full-thickness versus superficial closure of the breast parenchyma on the likelihood of subsequent infection and local recurrence after lumpectomy for early-stage breast cancer. In patients undergoing breast-conserving therapy (BCT), operative closure technique has been largely influenced by expected cosmetic outcome. However, the common practice of promoting postoperative fluid collection raises concerns about potential bacterial colonization, tumor cell migration, and impaired post-BCT surveillance. METHODS: From 1985 through 2004, operative closure technique was determined in 516 breasts in 580 women with stage T0-2N0-1 breast cancers undergoing BCT. Medical records were reviewed to determine closure technique, incidence of postoperative infection, and local recurrence characteristics. RESULTS: Median follow-up was 6.4 years from the completion of radiotherapy. The rate of acute infection was higher with the superficial closure technique: 11.7% (27/230) versus 5.2% (15/286) (P = .009). In T1-2 patients, there was no difference in the rate of local recurrence based on closure type: 5.6% (11/195) versus 3.5% (8/231) (P = .348). On multivariate analysis, acute infections and margin status were associated with increased local recurrence. Superficial closure was associated with larger recurrences less likely to be detected on mammogram. In stage T0-T2 patients, 80% of recurrent tumors after superficial closures were greater than 1 cm compared with no recurrent tumors greater than 1 cm after full-thickness closures (P = .005). In patients with superficial closure, 29% of recurrences in the tumor bed were initially detected on mammogram versus 100% in patients with deep closure (P = .003). CONCLUSIONS: Closure method was not predictive of local recurrence. Our findings regarding infection and post-treatment surveillance suggest, however, that full-thickness closure may be the preferred technique in BCT patients.

Infiltrating apocrine adenocarcinoma with extramammary pagetoid spread.

Apocrine adenocarcinoma is a rare malignancy with invasive potential. Its clinical behavior and histologic appearance are highly variable, making accurate diagnosis difficult. We report on a case of apocrine carcinoma presenting with lymph node infiltration and extensive extramammary Paget's disease. Wide local excision with lymph node dissection is the mainstay of treatment. The role of adjuvant therapy has yet to be established.

Idiopathic granulomatous mastitis: in search of a therapeutic paradigm.

Idiopathic granulomatous mastitis, also known as idiopathic granulomatous lobular mastitis, is a benign breast lesion that represents both a diagnostic and therapeutic dilemma. We report two cases of granulomatous mastitis recently evaluated and managed at our institution. To better understand this rare disease, we analyzed treatment outcomes in reported cases of granulomatous mastitis. One hundred sixteen cases were subsequently analyzed. Primary management strategies included observation (n = 9), steroids (n = 29), partial mastectomy (n = 75), and mastectomy (n = 3). Success rates with each treatment were observation, 56 per cent; steroids, 42 per cent; partial mastectomy, 79 per cent; and mastectomy, 100 per cent. Based on this analysis, we propose a clinically useful algorithm for both workup and management of these challenging cases.

Delayed breast cellulitis: an evolving complication of breast conservation.

PURPOSE: Delayed breast cellulitis (DBC) is characterized by the late onset of breast erythema, edema, tenderness, and warmth. This retrospective study analyzes the risk factors and clinical course of DBC. METHODS AND MATERIALS: From 1985 through 2004, 580 sequential women with 601 stage T0-2N0-1 breast cancers underwent breast conserving therapy. Cases of DBC were identified according to accepted clinical criteria: diffuse breast erythema, edema, tenderness, and warmth occurring >3 months after definitive surgery and >3 weeks after radiotherapy. Potential risk factors analyzed included patient comorbidity, operative technique, acute complications, and details of adjunctive therapy. Response to treatment and long-term outcome were analyzed to characterize the natural course of this syndrome. RESULTS: Of the 601 cases, 16%, 52%, and 32% were Stage 0, I, and II, respectively. The overall incidence of DBC was 8% (50/601). Obesity, ecchymoses, T stage, the presence and aspiration of a breast hematoma/seroma, removal of >5 axillary lymph nodes, and arm lymphedema were significantly associated with DBC. The median time to onset of DBC from the date of definitive surgery was 226 days. Ninety-two percent of DBC patients were empirically treated with antibiotics. Fourteen percent required more invasive intervention. Twenty-two percent had recurrent episodes of DBC. Ultimately, 2 patients (4%) underwent mastectomy for intractable breast pain related to DBC. CONCLUSION: Although multifactorial, we believe DBC is primarily related to a bacterial infection in the setting of impaired lymphatic drainage and may appear months after completion of radiotherapy. Invasive testing before a trial of antibiotics is generally not recommended.

Accuracy of intraoperative frozen-section analysis of breast cancer lumpectomy-bed margins.

BACKGROUND: My colleagues and I have been using intraoperative frozen-section analysis (FSA) to evaluate lumpectomy margins in an attempt to reduce the number of additional operations that patients with ductal carcinoma in situ or stage I and II breast cancer would have to endure. We review our experience in breast-conservation therapy (BCT) at the University of Florida (Gainesville) to determine the effectiveness of this approach. STUDY DESIGN: Operative reports, operative logs, and pathology reports were retrospectively reviewed for patients who had BCT from January 2001 to January 2004. Ninety-seven patients (116 operations) were reviewed. RESULTS: Nineteen patients required an additional operation (19.6%). Forty-three patients had positive margins on paraffin-embedded histologic analysis (44.3%). Accuracy of FSA was 84% when evaluated on a per-case basis, and 96% on a per-slide basis. False negatives were identified in 22 patients, affecting the operative pathway of 19 patients (19.6%) and were identified more frequently in cases of ductal carcinoma in situ (p < 0.001). There were no false positives. Additional operative time required for FSA was approximately 13 minutes per case. Eighty-four (86.6%) patients had successful BCT and 13 patients (13.4%) required mastectomy. CONCLUSIONS: Intraoperative analysis of margins using FSA is effective at minimizing the number of additional operations, with 19 patients benefiting from immediate intervention in this study. The authors believe that the number of second operations prevented and the high BCT rates justify performing FSA. Ductal carcinoma in situ is more difficult to identify in FSA. Preoperative discussions with the patient should reflect these findings.

Minimizing local recurrence after breast conserving therapy using intraoperative shaved margins to determine pathologic tumor clearance.

BACKGROUND: This study analyzed survival, locoregional recurrence, and reexcision rates after breast conserving therapy, based on the margin analysis technique used at the University of Florida, which incorporates frozen section analysis of shaved breast tissue from the lumpectomy cavity. STUDY DESIGN: A retrospective review was done of 257 patients who underwent 267 consecutive lumpectomy operations and completed radiation therapy at our institution. Margins in 189 patients were assessed using frozen section analysis of shaved margins from the lumpectomy cavity. RESULTS: Breast conserving therapy was performed for 220 (83%) patients with early breast cancer (T1 and T2 tumors) and 47 (17%) with ductal carcinoma in situ. With a median followup of 5.6 years, the crude locoregional recurrence rates for patients who had margins analyzed intraoperatively by frozen section analysis or margins analyzed by permanent analysis were 1.9% (3 of 157) and 3.1% (2 of 63), respectively, for early breast cancer and 15.6% (5 of 32) and 6.6% (1 of 15) for ductal carcinoma in situ (p=NS). Survival rates were 97% and 78%, at 5 and 10 years, respectively, for the early breast cancer patients, and 98% and 98%, respectively, for ductal carcinoma in situ patients. Permanent intraoperative frozen section analysis reexcision rates were 33.3% (26 of 78) and 5.8% (11 of 189). CONCLUSIONS: Regardless of the technique used for margin analysis, breast conserving therapy led to low locoregional recurrence relative to national figures, pointing to the importance of the technique of radiation therapy at our institution. Reexcision rate was reduced with the use of frozen section analysis.

Angiosarcoma after breast-conserving therapy: experience with hyperfractionated radiotherapy.

PURPOSE: To report our promising results of hyperfractionated radiotherapy (RT) in conjunction with surgery for angiosarcoma occurring after breast-conserving therapy for early-stage breast cancer. METHODS AND MATERIALS: Since 1997, 3 cases of angiosarcoma after breast-conserving therapy have been managed at the University of Florida. The histologic specimens in each case were reviewed and graded by one of us (J.D.R.). RESULTS: Explosive growth of discolored skin lesions coincident with histologic evidence of angiosarcoma characterized all 3 cases but was preceded by a fairly indolent period (almost 2 years) of atypical vascular hyperplasia in 2 patients. All 3 patients were treated initially with radical surgery for the angiosarcoma, but extensive recurrences were noted within 1 to 2 months of surgery. Because of the extremely rapid growth noted before and after surgery, hyperfractionated RT was used. Two of the patients underwent planned resection after RT, and neither specimen demonstrated any evidence of high-grade angiosarcoma. All 3 patients were alive without any recurrent disease 22, 38, and 39 months after treatment. CONCLUSIONS: Hyperfractionated irradiation appears to be effective treatment for rapidly proliferating angiosarcoma. For previously untreated angiosarcoma, we now recommend hyperfractionated RT followed by surgery to enhance disease control and remove as much reirradiated tissue as possible.

Pro- and antiinflammatory cytokine production after radiofrequency ablation of unresectable hepatic tumors.

BACKGROUND: Experience using radiofrequency ablation (RFA) for treating unresectable hepatic malignancies is expanding, with promising outcomes and fewer complications compared with cryotherapy. STUDY DESIGN: This study examined systemic inflammatory responses after RFA as measured by the appearance of postoperative symptoms and cytokine production. Seventeen patients (11 men, 6 women) aged 40 to 85 years (mean 64.2 years) with unresectable primary and metastatic hepatic tumors underwent RFA. Mean liver volume treated with RFA was 35.3% +/- 3.6% (SEM) (median 36.8%). Plasma cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-1ra, IL-6, IL-8, IL-10, p55, and p75) were measured from anesthesia induction through 48 hours after RFA. Ex vivo whole-blood cytokine production was measured at baseline, 24 hours, and 48 hours after RFA. RESULTS: Cytokine and cytokine-receptor production were not notably altered by RFA. Ex vivo whole-blood endotoxin stimulation indicated that intrinsic cellular immune function remained intact after treatment, although modest decreases in stimulated tumor necrosis factor alpha production were observed 24 to 48 hours after RFA. Variceal bleeding, hepatic failure, and death occurred in one patient 30 days after RFA. None of the remaining patients exhibited tachycardia or hypotension. Fevers (> or = 38.5 degrees C) developed in three patients during the first 48 hours postoperatively. There was no association between plasma cytokines and postoperative complications. CONCLUSIONS: In contrast to previous reports using cryotherapy, systemic inflammatory responses as measured by increased cytokines were not observed after RFA. The cryotherapy-induced "cryoshock" phenomenon was not observed in patients undergoing RFA in our study. We conclude that RFA ablation is fundamentally different than cryotherapy and apparently does not stimulate Kupffer and other hepatic macrophages to produce proinflammatory cytokines.

Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy.

BACKGROUND: Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN: Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS: Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS: In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.

Sequential dermal-peritumoral radiocolloid injection for sentinel node biopsy for breast cancer: the University of Florida experience.

Although sentinel lymph node (SLN) biopsy is rapidly becoming the standard of care for small breast cancers the optimal radiocolloid injection technique remains controversial. We report our experience with sequential dermal-peritumoral radiocolloid injection that takes advantage of both techniques. One hundred eighteen patients with clinical stage T(is), T1, T2 and N0 breast cancer underwent SLN biopsy at the University of Florida. Twelve to 18 hours before surgery patients received either an injection of 0.5 to 1.0 mCi 50:50 filtered:unfiltered technetium sulfur colloid into the dermis overlying the tumor and/or a peritumoral injection of a 3 to 4-mCi of radiocolloid 30 minutes later. Dynamic lymphoscintigraphy was performed and the topographical location of all imaged lymph nodes was marked on the skin. The next morning the surgeon utilized a hand-held gamma probe to remove all SLN(s) defined as any lymph node with radioactive counts 10 per cent or more of the ex vivo counts of the most radioactive SLN [internal mammary (IM) nodes were not removed]. The SLN identification rate was 98.5 per cent (3 IM nodes) for dermal injection (d.), 83.3 per cent (1 IM node) for peritumoral injection (p.), and 100 per cent (14 IM nodes) for sequential dermal-peritumoral injection (d.p.) (p < 0.05 DP versus D). Sequential d.p. 50:50 filtered:unfiltered technetium sulfur colloid injection results in a rapid, high SLN identification rate that persists until surgery the next morning. Delineation of nonaxillary SLNs may lead to more accurate breast cancer staging and may also influence the delivery of IM node radiation.

Antineoplastic therapy in colorectal cancer through proteasome inhibition.

Upregulation of nuclear factor (NF)-kappaB is found in many forms of cancer. Activation of NF-kappaB in cancer cells by chemotherapy or radiation can blunt the ability of this therapy to induce cell death. Proteasome inhibitors stimulate apoptosis in part via prevention of NF-kappaB activation. We sought to determine whether constitutive NF-kappaB activity is present in human colon cancer. In addition we studied whether alterations of NF-kappaB activity with a proteasome inhibitor would prevent colon cancer cell growth and induce apoptosis. We demonstrated constitutive transcriptional activation of NF-kappaB in SW48 and SW116 colon cancer cells by luciferase and electromobility shift assays. This was confirmed by p65 immunostaining. This activity was further induced in the presence of chemotherapy. In colon cancer specimens constitutive activation of NF-kappaB was observed in the majority of tumors. Treatment with the proteasome inhibitor (MG-132) inhibited growth and also stimulated apoptosis of colon cancer cells. We conclude that inhibition of NF-kappaB activation may be a logical therapy for certain cancers. This can be done via specific approaches on molecules necessary for keeping NF-kappaB inactivated in the cytoplasm. Other potentially useful ways to promote apoptosis in cancer cells include the utilization of proteasome inhibitors. Such inhibitors are currently being evaluated in clinical trials.

Breast Disease-Related Educational Outcomes at the University of Florida.

The purpose of this study was to assess resident knowledge related to breast disease at the University of Florida. In addition, we surveyed graduates of our surgery program regarding the importance of breast disease in their surgical practice and we determined if the completion of postgraduate courses on breast disease influenced patient outcome measures. In the decade of the 1990s, we compared the American Board of Surgery In-Service Training Examination (ABSITE) scores of residents rotating on the breast service in the 6 months immediately prior to examination (June-January) with those residents who had not rotated on the breast service within the 6 months leading up to the ABSITE examination. We also compared ABSITE scores of surgery residents at the University of Florida at Gainesville (breast service) to surgery residents at the University of Florida at Jacksonville (no breast service). Finally, we surveyed graduates of the general surgery program at the University of Florida at Gainesville (1980-1998) to determine the importance of breast disease in their practices and if the completion of postgraduate courses on breast disease influenced rates of breast conservation and immediate breast reconstruction. Residents who rotated on the breast service in the 6 months prior to the ABSITE had significantly fewer incorrect breast-related ABSITE questions than residents who had not rotated on the breast service. Those graduates who had taken postgraduate courses in breast disease responded that they were more likely to perform breast-conserving surgery. There was also a trend for graduates who had completed postgraduate courses on breast disease to respond that they were more likely to perform immediate breast reconstruction following mastectomy. Limiting breast surgery to a single service does not appear to improve resident accumulation and retention of breast disease-related knowledge. Graduates who complete postgraduate courses related to breast disease are more likely to perform breast-conserving surgery and immediate reconstruction following mastectomy. Since the management of breast disease comprises a significant part of general surgical practice, surgical educators must ensure adequate resident education and evaluation with respect to breast disease.