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."

Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program.

BACKGROUND: The Intrabeam (Carl Zeiss) brachytherapy device (IB) is an electronic brachytherapy device that can be used to deliver low energy x-rays (50 kV) to a lumpectomy cavity at the time of lumpectomy for breast cancer. Reported experience with IB for breast cancer in the United States has been extremely limited. Here we describe our experience and analyze the impact of IB on our multidisciplinary breast cancer program. STUDY DESIGN: This is a retrospective review of a prospectively collected breast cancer database. Patient characteristics, treatment characteristics, recurrence, and cosmesis were analyzed. Cost data were also analyzed to determine the impact of IB on the breast cancer program. RESULTS: Seventy-eight patients underwent 80 IB treatments in this series between November 2010 and October 2012. Most patients had invasive ductal carcinoma. Mean total operative time for patients receiving lumpectomy, sentinel node biopsy, and IB was 132 minutes (range 79 to 243 minutes). Intrabeam brachytherapy was the only adjuvant radiation required in 81% of patients, and only 15% of patients required additional operation after the index lumpectomy procedure. At 12 months of follow-up, cosmesis was good to excellent in 92% of patients. There have been no local recurrences in patients treated in this series. Intrabeam brachytherapy is associated with considerably lower costs ($1,857) than conventional whole breast radiation therapy ($9,653). CONCLUSIONS: Implementation of IB impacts treatment planning and operating room use in a multidisciplinary breast cancer program. The safety profile, ease of administration, and reduced costs of IB favor its more widespread use in selected patients with early-stage breast cancer.

The University of Florida Department of Surgery: building a stronger tomorrow on yesterday's foundation.

Established in 1957, the University of Florida Department of Surgery has a solid foundation on which current faculty are driven to build a stronger tomorrow. The department is focused on promoting patient-centered care, expanding its research portfolio to improve techniques and outcomes, and training the surgical leaders of tomorrow. It fosters an environment where faculty, residents, students, and staff challenge long-held traditions with the goal of improving the health of our patients, the quality of our care, and the vitality of our work environment.

Tumor endothelial marker 8 expression in triple-negative breast cancer.

BACKGROUND/AIM: Tumor endothelial marker 8 (TEM8) is a tumor endothelial-associated antigen that is having an increasingly recognized role in tumor biology. The expression of TEM8 in triple-negative breast cancer (TNBC) has not yet been characterized. MATERIALS AND METHODS: We hypothesize that TEM8 is overexpressed in TNBC and in metastatic TNBC in lymph nodes (LN) compared to normal breast tissue and normal lymphatic tissue, respectively. We studied expression of TEM8 in cases of primary (n=17) and metastatic (n=2) TNBC using immunohistochemical analyses. RESULTS: All cases demonstrated increased expression of TEM8 in tumor tissue compared to non-cancerous breast tissue. TEM8 was expressed at a higher level in the stroma adjacent to the TNBC in all cases, with focal immunoreactive areas within the tumor. TEM8 was not expressed in normal lymphoid tissue, but showed expression at sites of LN metastases. CONCLUSION: TEM8 would appear to represent a new biologic target for designing novel diagnostic or therapeutic approaches for TNBC.

Total parenteral nutrition and cancer: from the beginning.

The early development of total parenteral nutrition and its evolution as an adjunct to the nutritional, metabolic, and antineoplastic therapy of cancer patients is described. Examples related to the sine wave of responses to new data and discovery are placed in context to understand better past, present, and how and where to proceed in the future to achieve optimal results from multimodal comprehensive management of patients with malignancies. Practical and philosophic thoughts are proffered to justify continued, intensified, logical, controlled clinical studies directed toward establishing the most rational, safe, and effective use of total parenteral nutrition in treating patients with cancer.

Shave biopsy is a safe and accurate method for the initial evaluation of melanoma.

BACKGROUND: Shave biopsy of cutaneous lesions is simple, efficient, and commonly used clinically. However, this technique has been criticized for its potential to hamper accurate diagnosis and microstaging of melanoma, thereby complicating treatment decision-making. STUDY DESIGN: We retrospectively analyzed a consecutive series of patients referred to the University of Florida Shands Cancer Center or to the Moffitt Cancer Center for treatment of primary cutaneous melanoma, initially diagnosed on shave biopsy to have Breslow depth < 2 mm, to determine the accuracy of shave biopsy in T-staging and the potential impact on definitive surgical treatment and outcomes. RESULTS: Six hundred patients undergoing shave biopsy were diagnosed with melanoma from extremity (42%), trunk (37%), and head or neck (21%). Mean (± SEM) Breslow thickness was 0.73 ± 0.02 mm; 6.2% of lesions were ulcerated. At the time of wide excision, residual melanoma was found in 133 (22%), resulting in T-stage upstaging for 18 patients (3%). Recommendations for additional wide excision or sentinel lymph node biopsy changed in 12 of 600 (2%) and 8 of 600 patients (1.3%), respectively. Locoregional recurrence occurred in 10 (1.7%) patients and distant recurrence in 4 (0.7%) patients. CONCLUSIONS: These data challenge the surgical dogma that full-thickness excisional biopsy of suspicious cutaneous lesions is the only method that can lead to accurate diagnosis. Data obtained on shave biopsy of melanoma are reliable and accurate in the overwhelming majority of cases (97%). The use of shave biopsy does not complicate or compromise management of the overwhelming majority of patients with malignant melanoma.

Utilization of minimally invasive breast biopsy for the evaluation of suspicious breast lesions.

BACKGROUND: Percutaneous needle biopsy, also known as minimally invasive breast biopsy (MIBB), has become the gold standard for the initial assessment of suspicious breast lesions. The purpose of this study is to determine modern rates of MIBB and open breast biopsy. METHODS: The Florida Agency for Health Care Administration outpatient surgery and procedure database was queried for patients undergoing open surgical biopsy and MIBB between 2003 and 2008. RESULTS: Although there was an increase in the use of MIBB, the overall rate of open surgical biopsy remained high (∼30%). A reduction in the open biopsy rate from 30% to 10% could be associated with a charge reduction of >$37.2 million per year. CONCLUSIONS: The current rate of open surgical breast biopsy remains high. Interventions and quality initiatives are warranted, which could lead to a reduction in unnecessary operations for women, improved patient care, and a reduction in breast health care costs.

Recurrent retroperitoneal sarcoma: impact of biology and therapy on outcomes.

BACKGROUND: Local recurrence remains the major cause of death in patients with retroperitoneal sarcoma (RPS). There is no consensus regarding management of patients with recurrent RPS. STUDY DESIGN: We performed a retrospective review of patients with recurrent RPS managed at 2 tertiary care centers between 1983 and 2008. Presentation, treatments, and outcomes were analyzed. RESULTS: Seventy-eight patients were identified and analyzed. Sixteen patients (22%) presented with concurrent metastatic disease; survival in this subset of patients was poor (median 12 months). Forty-eight patients underwent resection of the first local recurrence of RPS. Palliation of tumor-related symptoms was achieved in 79% with operation. Survival was significantly better in patients having complete (p = 0.001) and incomplete resection (p = 0.02) compared with patients having biopsy only. Among patients with first local recurrence, high grade tumor (p = 0.0001) and no resection (p = 0.007) were significantly associated with reduced survival. On multivariate analysis, radiation therapy, multifocality, histologic subtype, and time to local recurrence did not significantly correlate with survival. Second and third local recurrences occurred at shorter intervals compared with first local recurrence and were less likely to be completely resectable. Patients undergoing resection of second and third local recurrences had survival similar to that in patients undergoing resection of first local recurrence. CONCLUSIONS: Tumor biology (high grade) is a significant prognostic factor for patients with recurrent RPS. Resection should be considered in patients with first and subsequent local recurrences (even if multifocal) of RPS because it is associated with improved survival. Operation should also be considered for palliation of symptoms in patients in whom resection is not possible.

Angiosarcoma after breast-conserving therapy: long-term outcomes with hyperfractionated radiotherapy.

BACKGROUND: With breast-conserving therapy (BCT) as the standard of care for patients with noninvasive and early stage invasive breast cancer, a small incidence of post-BCT angiosarcoma has emerged. The majority of therapeutic interventions have been unsuccessful. To the authors' knowledge, there is no consensus in the medical literature to date regarding the treatment of this malignancy. The current study was conducted to report the long-term outcomes of a novel approach using hyperfractionated and accelerated radiotherapy (HART) for angiosarcoma developing after BCT. METHODS: The authors retrospectively reviewed the outcomes of 14 patients treated with HART with or without surgery at the University of Florida between November 1997 and March 2006 for angiosarcoma that developed after BCT. RESULTS: At the time of last follow-up, 9 patients had remained continuously without evidence of disease for a median of 61 months after HART (range, 36-127 months). Five patients had further manifestations of angiosarcoma after HART at a median of 1 month (range, 1-28 months): 3 with progressive pulmonary and/or mediastinal disease that was likely present before HART and 2 with local or regional disease extension. Progression-free survival rates for the 14 patients at 2 years and 5 years were 71% and 64%, respectively. The overall and cause-specific survival rates were both 86% at 2 years and 5 years. CONCLUSIONS: To the best of the authors' knowledge, HART with or without subsequent surgery, as documented in the current series, is the first approach to provide a high rate of local control, disease-free survival, and overall survival after the development of post-BCT angiosarcoma. The authors believe the success noted with this approach is related to both the hyperfractionation and acceleration of the RT.

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.

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.

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.

Accuracy of breast cancer axillary lymph node treatment plans based on 2-dimensional imaging: what we should know before interpreting 2-dimensional treatment-planning era studies.

OBJECTIVE: To investigate axillary 2-dimensional treatment planning accuracy. METHODS: Computed tomography (CT) simulation data for 16 breast cancer cases taken after level I-II axillary dissection were analyzed. An additional 6 patients underwent CT simulation using the historical 90-degree position (HP), and the standard-bore CT position (CT-P). Two physicians identified the lateral and medial borders of the coracoid process (CCP) on digitally reconstructed radiography (DRR). The DRR-identified x coordinates were compared with the CT-measured x coordinates. x coordinates differences between the most medial surgical clip and the borders of the CCP as identified on CT were analyzed. Fields were designed to cover various amounts of the axilla, and treatment plans were generated to compare doses to the most medial surgical clip. RESULTS: In 11 and 6 cases for each physician, respectively (lateral border), and in all cases for both physicians (medial border), the DRR identification of the CCP was medial to that on CT. In 9 and 8 cases, the most medial surgical clip was lateral to the medial and lateral borders of the CCP, respectively. In all data sets, the average difference was larger in the HP compared with CT position. The number of patients who received more than 90% of the prescribed dose when using the plans with the mid humeral head border, lateral border of the CCP, and medial border of the CCP were as follows: 6, 1, and 0, respectively. CONCLUSIONS: When using 2-dimensional treatment planning, the dose to the undissected axilla can vary depending on the anatomic landmark used to define the lateral border of the axillary field. This may account for outcome differences found in older radiotherapy studies.

Reoperative surgery in sporadic Zollinger-Ellison Syndrome: longterm results.

BACKGROUND: Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES. STUDY DESIGN: We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies. RESULTS: Fifty-two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma. CONCLUSIONS: Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted.

Magnetic resonance imaging for axillary staging in patients with breast cancer.

PURPOSE: To determine the utility of MRI for assessing axillary lymph node status in patients with breast cancer. MATERIALS AND METHODS: A consecutive series of patients who underwent breast MR before surgical management of breast cancer with axillary sampling between 2005 and 2007 were identified. MRs were evaluated for the number of nodes, contrast kinetics, nodal area, and number of nodes with no fatty hilum. Data were analyzed in the context of final breast pathology, sentinel lymph node status, and axillary nodal status. Correlations were analyzed using Kendall's tau-b test. Reported P values are one-sided. RESULTS: Fifty-six females (median = 58 years) were studied. Sentinel lymph nodes (SLN) were positive in 15/56 patients (27%). All SLN + patients (n = 15) had completion axillary dissection. Extent of nodal disease was 1 (n = 3), 2 (n = 4), >2 (n = 8). Presence of any axillary lymph node with no fatty hilum and the number of nodes with no fatty hilum on MR significantly correlated with pathologic node positivity (P = 0.04); while kinetics, node number, and node size did not correlate. CONCLUSION: Breast MR may be useful in the assessment of axillary nodes in patients with breast cancer.

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.

The dynamic tumor bed: volumetric changes in the lumpectomy cavity during breast-conserving therapy.

PURPOSE: To characterize the magnitude of volume change in the postoperative tumor bed before and during radiotherapy, and to identify any factors associated with large volumetric change. METHODS AND MATERIALS: Thirty-six consecutive patients with early-stage or preinvasive breast cancer underwent breast-conserving therapy at our institution between June 2006 and October 2007. Computed tomography (CT) scans of the breast were obtained shortly after surgery, before the start of radiotherapy (RT) for treatment planning, and, if applicable, before the tumor bed boost. Postoperative changes, seroma, and surgical clips were used to define the tumor bed through consensus agreement of 3 observers (B.P., D.I., and J.L.). Multiple variables were examined for correlation with volumetric change. RESULTS: Between the first and last scan obtained (median time, 7.2 weeks), the tumor bed volume decreased at least 20% in 86% of patients (n = 31) and at least 50% in 64% of patients (n = 23). From the postoperative scan to the planning scan (median time, 3 weeks), the tumor bed volume decreased by an average of 49.9%, or approximately 2.1% per postoperative day. From planning scan to boost scan (median interval, 7 weeks), the median tumor bed volume decreased by 44.6%, at an average rate of 0.95% per postoperative day. No single factor was significantly associated with a change in tumor bed volume greater than 20%. CONCLUSIONS: The average postlumpectomy cavity undergoes dramatic volumetric change after surgery and continues this change during RT. The rate of change is inversely proportional to the duration from surgery. In this study no factors studied predicted large volumetric change.