Metastatic Acral lentiginous melanoma: A case report and review.

Of the four subtypes of cutaneous melanoma, acral lentiginous melanoma (ALM) is atypical in its presentation. ALM is a rare melanoma subtype that presents on the volar surfaces of the hand and foot. The difficulty of making an early diagnosis of ALM is highlighted by the case seen in our institution. The dire prognosis associated with ALM is postulated to be not only related to its destructive nature, but also due to a lack of patient awareness and vigilance, inadequate physician awareness, and disparity in healthcare access. We present this as a unique account of an ALM lesion in a 76 year old African-American male presenting originally in the left foot that went misdiagnosed for several years. The original lesion was considered to be an ulcerating left great toe lesion with signs typical of osteomyelitis. These clinical findings were corroborated by radiological x-ray evidence. Upon amputation and biopsy for suspected worsening osteomyelitis five years later, the pathological diagnosis of melanoma was finally made.

Strong association of fascin expression with triple negative breast cancer and basal-like phenotype in African-American women.

BACKGROUND: Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma. OBJECTIVE: To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent. METHODS: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival. RESULTS: We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston-Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression. CONCLUSION: These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.

T4b breast masses: a retrospective review of 12 cases presenting to a metropolitan tertiary care center.

INTRODUCTION: Due to increased awareness of breast cancer resulting in early detection, there is a decreased incidence nationwide of late-stage breast cancer, including that which presents with skin involvement (T4b). METHODS: A retrospective analysis of a 10-month period from August 2007 to May 2008 at Howard University Hospital (HUH), Washington, DC, revealed 12 patients diagnosed with T4b breast cancer and compared to similarly staged patients in the Surveillance, Epidemiology, and End Results (SEER) database. Finally, a logistic regression for the likelihood of T4b diagnosis was performed patients in the SEER database. RESULTS: HUH patients with T4b tumors were more likely than SEER patients to present with predictors of poor clinical outcome, including high-grade histology (100% vs 59.4%, p = .04) and estrogen receptor- (75% vs 30.3%, p = .001) and progesterone receptor- negative (91.7% vs 43.9%, p = .001) status. Conversely, HUH patients were younger (57.8 y vs 66.3 y, p = .03) and had smaller tumors (11.1 cm vs 28.2 cm, p = .02) than SEER patients with similarly staged tumors. Older patients (OR, 2.36; 95% CI, 1.50-2.00; p < .001; 60-80 y), African American patients (OR, 1.63; 95% CI, 1.26-2.11; p < .001), and patients with high-grade (OR, 5.51; 95% CI, 3.88-6.52; p < .001) tumors were more likely to be diagnosed with T4b tumors, whereas patients who lived in an area with increased median household income (OR, 0.99; 95% CI, 0.99-0.99; p = .001) were less likely to be diagnosed with a T4b lesion. CONCLUSION: While much research has focused on the socioeconomic causes for the development of T4b tumors, both patient and tumor biologic conditions cannot be eliminated as causative agents.

Early-stage gallbladder cancer in the Surveillance, Epidemiology, and End Results database: effect of extended surgical resection.

HYPOTHESIS: Extended surgical resection (ESR) may improve survival in patients with early-stage primary gallbladder cancer. DESIGN: Retrospective analysis of findings in the Surveillance, Epidemiology, and End Results (SEER) database. SETTING: Academic research. PATIENTS: Individuals with potentially surgically curable gallbladder cancer (Tis, T1, or T2) who underwent a surgical procedure. MAIN OUTCOME MEASURES: Overall survival, number of lymph nodes (LNs) excised, and results of simple cholecystectomy vs ESR. RESULTS: We identified 3209 patients with early-stage gallbladder cancer (11.7% Tis, 30.1% T1, and 58.2% T2). On multivariate analysis, decreased survival was noted among patients older than 60 years (hazard ratio, 1.57; 95% confidence interval, 1.30-1.90), among patients with more advanced cancer (1.99; 1.46-2.70 for T1; 3.29; 2.45-4.43 for T2), and among patients with disease-positive LNs (1.65; 1.39-1.95 for regional; 2.58; 1.54-4.34 for distant) (P < .001 for all), while increased survival was observed among female patients (0.82; 0.70-0.96; P = .02) and among patients undergoing ESR (0.59; 0.45-0.78; P < .001). The survival advantage of ESR was seen only in patients with T2 lesions (0.49; 0.35-0.68; P < .001). Lymph node excision data were available for a subset of 2507 patients, of whom 68.2% had no LN excised, 28.2% had 1 to 4 LNs excised, and 3.6% had 5 or more LNs excised. On multivariate analysis, patients with 1 to 4 LNs excised had a survival benefit over those with no LN excised (HR, 0.55; 95% CI, 0.46-0.66; P < .001), and patients with 5 or more LNs excised had a survival benefit over patients with 1 to 4 LNs removed (0.63; 0.40-0.96; P = .03). Lymph node excision improved survival in patients with T2 lesions (0.42; 0.33-0.53; P < .001 for patients with 1-4 LNs excised). CONCLUSION: Extended surgical resection, LN excision, or both may improve survival in certain patients with incidentally discovered gallbladder cancer.

Pediatric trauma at an adult trauma center.

BACKGROUND: Accidental traumatic injury is the number 1 cause of morbidity and mortality in the pediatric population. In this study, we aim to prove that certain pediatric patients can be treated with good outcomes at an adult level 1 trauma center. METHODS: Retrospective analysis using the Howard University Hospital trauma registry identified 71 patients treated at Howard University Hospital between the ages of 1 and 17 years old. Specific variables were identified and collected for each patient. RESULTS: The majority of pediatric traumas treated at Howard University Hospital between June 2004 and May 2005 had high survival rates (93%). The patients who did not survive (7%) included 3 patients who were dead on arrival and 2 who died shortly after arrival to the hospital. CONCLUSIONS: Certain pediatric populations who present with minor and/or isolated injuries can be treated in an adult level 1 trauma center with similar outcomes to treatment in a pediatric level 1 trauma center.

The number of lymph nodes examined debate in colon cancer: how much is enough?

BACKGROUND: Much debate exists over the significance of the number of lymph nodes (LN) examined after colon resection. MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) database was queried for patients who presented with colonic adenocarcinoma. Multiple Cox proportional hazard regressions were run using successive LN cut-offs (6-26), first controlling for and then stratifying by T-stage. This was repeated in subsets of patients delineated by LN status. Additional variables controlled for in every regression were age, gender, ethnicity, marital status, number of positive LN, grade, metastases, and extent of surgery. After each regression, a Harrell's C statistic and an Akaike's information criterion (AIC) were performed to test the predictive capacity and fit of the model, respectively. RESULTS: 128,071 patients met selection criteria. The highest Harrell's C statistics among all patients were the cutoffs at 14 LN and 15 LN. Between those, the AIC shows that the cutoff at 15 LN fit the data more closely than the 14 LN cutoff. The models with the best predictive ability and best fit by T-stage were T1, 14 LN; T2, 10 LN; T3, 10 LN; T4, 12 LN. CONCLUSIONS: Using a population-based dataset, we show the optimal number of LN examined is dependent upon the patient's tumor stage. Across all T-stages, the highest optimal number of LN resected was 15. Since it is possible to estimate but not perfectly predict the stage of a patient's tumor preoperatively, we believe the recommendation should be based on the most conservative measure.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Disparity in limb-salvage surgery among sarcoma patients.

BACKGROUND: Recent studies have shown that aggressive preoperative radiation increases the likelihood of limb salvage in sarcoma patients. METHOD: The Surveillance, Epidemiology and End Results database was used to run an adjusted logistic regression for the receipt of cancer-directed treatment modalities. RESULTS: Of patients with specific surgical procedures recorded (n = 2,104), 86.0% had undergone a limb-sparing procedure. On bivariate analysis, African American patients were less likely to receive a limb-sparing procedure than white patients (80.4% vs 86.9%; P = .02). On multivariate analysis, African Americans were significantly more likely to receive preoperative radiation (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.22-4.40; P = .011), yet this did not translate into an increase in limb salvage (OR, .67; 95% CI, .42-1.08; P = .10). Limb salvage significantly increased for all groups in 2001 and after (OR, 2.75; 95% CI, 1.55-4.88; P = .001) without a decrease in survival. For those with tumors greater than 4 cm, there was a trend away from limb salvage for African Americans (OR, .59; 95% CI, .32-1.07; P = .08). CONCLUSIONS: Our results of an increase in limb-salvage surgeries after 2001 without a decrease in survival support previous studies. The trend away from limb salvage for African Americans cannot be answered by this study.

Predictors for survival of penetrating trauma using emergency department thoracotomy in an urban trauma center: the Cardiac Instability Score.

BACKGROUND: Emergency department thoracotomy (EDT) is a procedure used in an attempt to save lives of patients in extremis. This study aims to determine predictors of survival and futility by proposing a scoring scale that measures cardiac instability and its use in predicting survival of victims of penetrating trauma undergoing EDT. METHODS: This retrospective study analyzes patients who underwent EDT during a 45-month period at Howard University Hospital, Washington, DC. Vital signs and Glasgow Coma scale (GCS) scores were analyzed at the scene and in the emergency department. A cardiac instability score (CIS) was devised to assign values to vital signs, and the GCS was based on scores from the emergency department. RESULTS: Emergency department vital signs, female gender, absence of cardiopulmonary resuscitation (CPR), and high CIS were found to be statistically significant predictors of survival. CONCLUSIONS: The CIS correlated with survival of patients who underwent EDT and was found to be statistically significant in determining the outcome of an EDT.

Academic needs in developing countries: a survey of the West African College of Surgeons.

BACKGROUND: The inaugural Fundamentals of Surgical Research Course was held in Sierra Leone in conjunction with the West African College of Surgeons (WACS). We subsequently performed a formal assessment of the academic needs of West African surgeons to plan for future courses, and hypothesized that they would differ from the goals of the U.S. course. METHODS: A survey was distributed via email to members of the WACS and returned by the same mechanism. It consisted of 6 questions addressing specific elements of the inaugural course, and potential new topics for future courses. RESULTS: Over half (53%, 25/47) of the respondents had not attended the inaugural course, while 85% (40/47) planned on attending the next course. Respondents identified least useful topics from the initial course as "Molecular Biology: Tools of the Trade" (45%, 21/47) and "Getting Promoted" (23%, 11/47). The least popular potential new topics were "Use and Abuse of Administrative Databases" (9%, 4/47), "Animal Models" (21%, 10/47), and "Genomics and Proteomics" (21%, 10/47). CONCLUSIONS: The self-reported academic needs of West African surgeons are oriented toward clinical research. Basic and translational research topics are of secondary interest to the majority of respondents. Future courses in this region must address specific local needs.

Breast cancer risk assessments comparing Gail and CARE models in African-American women.

The Gail model has been used to predict invasive breast cancer risk in women using risk factors of age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, and number of previous benign breast biopsies. However, this model underestimates breast cancer risk in African-American women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in African-American women. In a sample of 883 women who participated in the breast cancer screening program at Howard University Cancer Center, we compared the breast cancer risk estimates from the Gail model and the CARE model. The mean 5-year breast cancer risk was 0.88% (Range: 0.18-6.60%) for the Gail model and 1.29% (Range: 0.20-4.50%) for the CARE model. Using the usual cutoff-point of 1.67% or above for elevated risk, there is a significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar's test, p < 0.0001). For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p < 0.0001). Our results confirm the need for validation of the Gail model in African-Americans and diversity in research. Although these findings are not perfect and perhaps not definitive, they are additive in the discussions during counseling and risk assessment in African-Americans. Furthermore, these findings will be complemented by new technologies such as genomics in refining our ability to assess risk.

Carcinoid of the ampulla of Vater: morphologic features and clinical implications.

Carcinoids involving the ampulla of Vater are rare lesions that may produce painless jaundice. The published data indicate that these tumors, in contrast to their midgut counterparts, metastasize in approximately half of cases irrespective of primary tumor size. Therefore, radical excision in the form of pancreaticoduodenectomy is recommended regardless of tumor size. As with other gastrointestinal carcinoid tumors, biological treatment with octreotide analogues can be applied to symptomatic patients. Tumor-targeted radioactive therapy is a newly emerging treatment option. We here report case of a carcinoid tumor of the ampulla of Vater presenting as painless jaundice in a 65-year old man and review the relevant literature, giving special attention to the morphologic features, clinical characteristics, and treatment modalities associated with this disease process.

Overexpression of tropomysin-related kinase B in metastatic human pancreatic cancer cells.

PURPOSE: Pancreatic adenocarcinoma is currently the fourth leading cause of cancer death in the United States, and most pancreatic cancers develop locally advanced disease or metastasis at the time of diagnosis. The mechanisms by which it invades and metastasizes are not known. EXPERIMENTAL DESIGN: To identify the genes involved in pancreatic cancer metastasis, we analyzed the gene expression profiles between highly metastatic Colo357L3.6pl and parental Colo357FG pancreatic cancer cell lines using cDNA microarrays and confirmed differential gene expression by reverse transcription-PCR, Western blotting, and immunologic analysis of 54 samples from pancreatic cancer patients. The correlation with clinical outcome was also examined. The possible signaling pathways involved with tropomyosin-related kinase B (TrkB) were analyzed. RESULTS: Our findings showed that TrkB was overexpressed in the highly metastatic Colo357L3.6pl cells, which correlated with perineural invasion (P = 0.026), positive retroperitoneal margin (P = 0.0005), and shorter latency to development of liver metastasis (Cox proportional hazard ratio, 0.3; 95% confidence interval, 0.1-0.8; P = 0.01) in patient samples. Extracellular signal-regulated kinases 1 and 2 were activated and Elk-1 and AP-1 DNA binding activity was induced in Colo357L3.6pl cells. Furthermore, interleukin 8 and vascular endothelial growth factor were more strongly expressed in Colo357L3.6pl than Colo357FG cells, and these findings were confirmed in Colo357L3.6pl and Colo357FG orthotopic tumors. CONCLUSION: These results suggest that overexpression of TrkB and activation of mitogen-activated protein kinase and AP-1, which may in turn induce the expression of vascular endothelial growth factor and interleukin 8, may mediate the cardinal clinical features of locally aggressive growth and metastasis of pancreatic cancer. Our results also imply that TrkB receptor may be a novel therapeutic target for pancreatic cancer.