Alfredo A. Santillan

PET/CT Fusion Scan Enhances CT Staging in Patients with Pancreatic Neoplasms

BackgroundThe role of fusion positron emission tomography/computed tomography scans (PET/CT) in staging of patients with pancreatic neoplasms (PN) is poorly defined. PET/CT may serve as an adjunct to standard imaging by increasing occult metastases detection. The purpose of this study was to assess the additional value, in relation to computed tomography (CT), of PET/CT imaging for patients with PN.MethodsEighty-two patients with potentially resectable PN underwent staging with PET/CT and CT of the chest and abdomen. Sensitivity of diagnosing pancreatic cancer by PET/CT avidity was evaluated. The sensitivity of detecting metastases was compared between PET/CT, standard CT, and the combination of PET/CT and CT. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT.ResultsThe sensitivity and specificity of PET/CT in diagnosing pancreatic cancer were 89% and 88%, respectively. Sensitivity of detecting metastatic disease for PET/CT alone, standard CT alone, and the combination of PET/CT and CT were 61%, 57%, and 87%, respectively. Findings on PET/CT influenced the clinical management in seven patients (11%), two with a supraclavicular lymph node (LN), two occult liver lesions, two peritoneal implants, and one peri-esophageal LN.ConclusionThis study evaluated PET/CT in the initial work-up of patients with PN. PET/CT increased sensitivity (87%) for detection of metastatic disease when combined with standard CT. In invasive cancer, PET/CT changed the management in 11% of our patients. PET/CT should be considered in the initial work-up of patients with potentially resectable pancreatic lesions.

Pathology Review of Thin Melanoma and Melanoma in Situ in a Multidisciplinary Melanoma Clinic: Impact on Treatment Decisions

PURPOSE Patients with thin melanoma (<or= 1.0 mm) and melanoma in situ (MIS) represent the majority of newly diagnosed melanoma. We estimated the impact of expert review of outside pathology material on the staging and thus treatment decisions affecting patients referred to a multidisciplinary clinic with early-stage melanoma. PATIENTS AND METHODS We studied patients with a diagnosis of thin melanoma or MIS referred to H. Lee Moffitt Cancer Center from 2006 to 2009. After comparing the referring laboratory and in-house dermatopathologic interpretations, we calculated any differences in diagnosis and tumor staging and the potential impact of differences in diagnosis and staging on prognosis and surgical treatment using the National Comprehensive Cancer Network clinical guidelines. RESULTS The overall pathologic discordance rate in diagnosis was 4% (15 of 420 patients; 95% CI, 2% to 6%). The overall change in tumor staging rate was 24% (97 of 405 patients; 95% CI, 20% to 28%). Pathology review led to changes in surgical excision margins in 12% of patients (52 of 420 patients; 95% CI, 9% to 16%) and in the decision about whether to perform a sentinel lymph node biopsy in 16% of patients (67 of 420 patients; 95% CI, 13% to 20%). Key pathologic factors, particularly mitotic rate, were frequently missing from outside pathology reports. CONCLUSION Our data suggest that review of thin melanoma or MIS by an expert dermatopathologist results in frequent, clinically meaningful alterations in diagnosis, staging, prognosis, and surgical treatment. Referral of these patients to a multidisciplinary melanoma clinic is appropriate, and management of such patients should include review of the biopsy whenever feasible.

Feasibility of Sentinel Lymph Node Biopsy Through an Inframammary Incision for a Nipple-Sparing Mastectomy

BackgroundNipple-sparing mastectomy (NSM) via an inframammary (IM) incision has been described for selected patients with breast cancer. However, the application of sentinel lymph node (SLN) mapping via an IM incision for NSM has yet to be reported. The objective of this study is to determine the technical feasibility of performing SLN through an IM incision without making an axillary counterincision.MethodsWe retrospectively reviewed our single-institutional experience with SLN biopsy and NSM through IM incisions between January 2006 and March 2008. Clinicopathologic factors were analyzed regarding indications, technical details, postoperative morbidity, and follow-up.ResultsFifty-two patients underwent 87 NSM through an IM incision (17 unilateral, 35 bilateral) with immediate reconstruction and SLN biopsy. Indications for surgery included invasive breast cancer (n = 21), ductal carcinoma in situ (DCIS) (n = 18), and prophylactic (n = 48). Mean tumor size of invasive carcinoma was 2.1 cm. The mean mastectomy specimen weight was 437 g. Subareolar injection consisted of blue dye (n = 43), technetium sulfur colloid (n = 2), or combination injection (n = 42). SLN biopsy through an IM incision was successfully performed in 84 of 87 cases (96.6%). A mean of 2.8 SLN were removed with a positive sentinel node encountered in 8 of 21 patients (38%) with invasive cancer. No complications were observed regarding the SLN portion of the operation. With a median follow-up of 6.5 months (range, 0.4–23 months), there have been no axillary local recurrences.ConclusionSLN biopsy can be performed through an IM incision during a NSM, avoiding a secondary axillary incision.

Phyllodes tumors: race-related differences.

BACKGROUND Phyllodes tumors (PT) are rare breast malignancies accounting for 0.5% to 1% of all breast tumors. PT have unpredictable behavior, with recurrence rates as high as 40%. A dearth of information exists about racial differences; elucidation of these differences is the objective of this study. STUDY DESIGN A retrospective review of patients treated for PT at either Moffitt Cancer Center or University of Texas Health Science Center San Antonio from 1999 to 2010. RESULTS Of the 124 patients, 71 (57%) were treated at Moffitt Cancer Center and 53 (42%) at University of Texas Health Science Center San Antonio. Mean age at diagnosis was 44 years (15 to 70 years). Thirty-three patients required mastectomy. Combining both cohorts, 42% of the patients were Caucasian, 43% were Hispanic, and 12% were black. Tumors were benign in 49% patients, borderline in 35%, and malignant in 16%, with a higher percentage of borderline and malignant tumors in Hispanic patients (p < 0.01). Hispanic patients tended to have larger tumors and higher mitotic rates (p = 0.01; p = 0.03). At a median follow-up time of 13 months, the local recurrence rate (6.4%) was associated with tumor size, tumor grade, mitotic rate, and close margin status (<2 mm) (p <0.01; p = 0.01; p = 0.01; p = 0.04). However, these findings did not translate into a survival difference by race. CONCLUSIONS In this multi-institutional review of PT we found substantial pathologic differences by race with higher-grade tumors present more often in Hispanic patients. These differences did not substantially affect outcomes at short-term follow-up. Further investigation into additional molecular, biologic factors, geographic impact, and socioeconomic factors is needed to more clearly delineate this finding.

The surgical treatment of breast cancer in the elderly: a single institution comparative review of 5235 patients with 1028 patients ≥70 years.

Abstract:  As the wave of the baby boomers shifts the age demographic of patients, the current surgical management of breast cancer in elderly women (≥70 years of age) becomes relevant because deviation from standard treatment often occurs in this group. The purpose of this study was to determine the operative mortality when treated with standard surgical procedures and to investigate trends in the surgical management of breast cancer in the elderly. A total of 5,235 patients undergoing either mastectomy or breast conservation surgery (BCS) for invasive and ductal carcinoma in situ (DCIS) were identified in a retrospective review of a prospectively accrued data base between the years of 1994 and 2007 at the Moffitt Cancer Center. Of the 5,235 patients, 1,028 (20%) patients were ≥70 years of age. The 30‐day and 90‐day mortality in the elderly group (age ≥70 years) was 0.2% (95% CI 0.02–0.7%) and 0.7% (95% CI 0.3–1.4%), respectively. The 30‐day and 90‐day mortality among patients <70 years was 0 and 0.05% (2 of 4,207 patients) (95% CI 0.005–0.2), respectively. BCS rates for invasive carcinomas were the highest for patients between 40 and 70 years of age, whereas the mastectomy rates were higher among patients <40 years of age (53%). Elderly women were as likely as women <40 years to have BCS for invasive carcinoma (OR 1.1, 95% CI 0.8–1.5), but more likely to have BCS for DCIS (OR 1.9, 95% CI 1.1–3.3). Surgical mortality in elderly women treated for breast cancer was extremely low and was related to the extent of surgery performed. Breast cancer treatment differed by age groups.

Management of Familial Melanoma and Nonmelanoma Skin Cancer Syndromes

The clinical manifestations of hereditary skin cancer syndromes depend upon the interplay between environmental and genetic factors. Familial melanoma occurs in the setting of hereditary susceptibility, with a complex phenotype of early age of onset, multiple atypical moles, multiple primary melanomas, multiple melanomas in the family, and in some instances pancreatic cancer. Identification of individuals who may have a hereditary susceptibility for the development of melanoma is essential to provide an opportunity for primary prevention, and to target high-risk groups for early diagnosis and treatment. Consequently, the surgeon as one of the primary caregivers should be familiar with hereditary skin cancer syndromes and their pathogenesis, diagnosis, management, and surveillance recommendations. This article discusses a practical approach for some of the issues likely encountered by the surgeon in the management of familial melanoma and non-melanoma skin cancer.

Modern multimodality therapy for pediatric nonorbital parameningeal sarcomas.

Nonorbital parameningeal sarcomas are rare, aggressive tumors that arise predominantly in the pediatric population. The purpose of this study was to review their management and to clarify the role of surgery in their treatment.

Association of radiotherapy with preferential depletion of luminal epithelial cells in a BRCA1 mutation carrier

Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among BRCA1 mutation carriers. However, the exact mechanism by which RT reduces incidence of BRCA1-associated cancer remains unclear. Here we studied fresh breast tissue from a BRCA1 mutation carrier who was initially treated with a lumpectomy and RT for a unilateral cancer and two years later chose a prophylactic bilateral mastectomy while remaining cancer-free. Flow cytometry analysis demonstrated a strikingly lower luminal cell population in the irradiated breast as compared to the non-irradiated breast, which was confirmed by immunohistochemistry. Furthermore, the irradiated breast tissue exhibited very low progenitor cell activity in vitro. Given the emerging evidence that BRCA1 tumors originate from luminal progenitor cells, our observations suggest that preferential and long-lasting elimination of luminal ductal epithelium may partly underlie the mechanism of RT-associated reduction in recurrence of BRCA1-associated cancer.

Isolated limb infusion for melanoma: a less morbid alternative to hyperthermic isolated limb perfusion in the US.

Melanoma in-transit metastases are subcutaneous or cutaneous lesions that develop within regional dermal and subdermal lymphatics prior to reaching the regional nodal basins. The risk of developing in-transit metastases after wide excision of primary melanoma is up to 10% [1]. The prognosis for in-transit metastases is similar to that of patients with multiple nodal metastases, with 5-year survival rates of 27 – 47% [2]. Therapeutic options for locoregional control in this patient population are based on volume and location of disease of the affected extremity. Surgical resection remains the preferred approach when all the disease can be excised without compromising cosmesis and function of the limb. However, when surgery is not feasible because of high bulky tumor burden and nodules that are not clustered together in the same location, other options exist, such as regional therapies with either hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI). Since the initial description of HILP in 1958 by Creech et al. [3], there have been only few modifications to this regional therapy for advanced extremity melanoma. This is a result of an accepted modality that has been successfully used for the last 50 years with complete response rates of 40 – 80% [4-6]. Recent results from the American College of Surgeons Oncology Group Z0020 trial revealed a complete response rate of 25% in patients undergoing HILP with melphalan alone and 26% when melphalan was combined with TNF [7]. This trial was ended early after interim analysis showed a lack of added efficacy with the addition of TNF and the significantly increased morbidity seen in the TNF group (16 vs 4% grade IV adverse events). Furthermore, morbidity from HILP can be significant and is due to the local effects of the chemotherapy itself, the application of hyperthermia, systemic leakage of the chemotherapy from the isolated limb or the surgical intervention [8]. These factors have led to the development of new regional therapeutic strategies in advanced extremity melanoma, such as ILI. ILI was introduced in the late 1990s at the Sydney Melanoma Unit (SMU) by Thompson et al. [9,10] with the objective of obtaining the benefits of HILP without incurring its major disadvantages and surgical morbidity. ILI and HILP techniques are different in several ways. ILI is a minimally invasive non-oxygenated low flow, normothermic or slightly hyperthermic infusion of chemotherapy with manual extraction of venous outflow. HILP is a maximally invasive procedure, involving open cannulation of the vessels at the root of the extremity. It is a complex, high flow and hyperthermic regional perfusion. While both techniques involve the addition of hyperthermia, the higher flow rates obtained with HILP allow the extremity to heat up faster and circulation of melphalan starts at 38.5 C, while with ILI, treatment is started when the extremity reaches ~ 37 C. The ILI perfusate environment is hypoxic and acidotic unlike HILP, where, using a bypass machine, the acid–base

Hereditary Breast Cancer Syndromes

Breast cancer represents a major public health problem in the world. According to the GLOBOCAN database, breast cancer is the second most common cancer in the world and the most common cancer among women, accounting for an estimated 1,152,161 new cases each year and 411,093 cancer deaths per year (Fig. 4.1) [1]. In the United States, breast cancer is the second leading cause of cancer death among women after lung cancer [2]. Recent trends in the incidence of female breast cancer have shown a sharp decrease during the period of 1999–2003. This can be partly explained by the increased utilization of screening mammography, better technologies that increase the sensitivity of detection suspicious abnormalities, and an overall reduction in the use of hormone replacement therapy (Fig. 4.2) [3]. Despite this recent decrease in breast cancer incidence, it is estimated that in the year 2007, more than 178,480 women will be diagnosed with breast cancer in the United States, with approximately 40,460 women dying from this disease. Of these, about 5–10% of the total breast cancer burden will be hereditary, having affected approximately 8,924–17,848 patients during 2007 [2].