Leptin-Notch signaling axis is involved in pancreatic cancer progression.

Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2). Leptin treatment increased cell cycle progression and proliferation, and the expression of Notch receptors, ligands and targeted molecules (Notch1-4, DLL4, JAG1, Survivin and Hey2), PCSC markers (CD24/CD44/ESA, ALDH, CD133, Oct-4), ABCB1 protein, as well as tumorsphere formation. Leptin-induced effects on PC and tumorspheres were decreased by IONP-LPrA2 and DAPT. PC cells secreted leptin and expressed the leptin receptor, OB-R, which indicates a leptin autocrine/paracrine signaling loop could also affect tumor progression. IONP-LPrA2 treatment delayed the onset of MiaPaCa-2 xenografts, and decreased tumor growth and the expression of proliferation and PCSC markers. Present data suggest that leptin-Notch axis is involved in PC. PC has no targeted therapy and is mainly treated with chemotherapy, whose efficiency could be decreased by leptin and Notch activities. Thus, the leptin-Notch axis could be a novel therapeutic target, particularly for obese PC patients.

CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition.

BACKGROUND: Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway. METHODS: Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20. RESULTS: CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, ß-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential. CONCLUSIONS: Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.

Situs inversus.

Situs Inversus is a rare condition with unique clinical and radiographic characteristics. We present a case highlighting important clinical factors associated with Situs Inversus.

Triple Negative Breast Cancer - An Overview.

Triple Negative Breast Cancer (TNBC) is a heterogeneous disease that based on immunohistochemistry (IHC) is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative. TNBC is typically observed in young AA women and Hispanic women who carry a mutation in the BRCA1 gene. TNBC is characterized by a distinct molecular profile, aggressive nature and lack of targeted therapies. The purpose of this article is to review the current and future novel signalling pathways as therapeutic approaches to TNBC. Recent Identification of a new BRCA1 trafficking pathway holds promise in the future for the development of targeted therapies for TNBC.

Subungual melanoma: diagnosis and management.

Subungual Melanoma accounts for less than three percent of all cutaneous melanomas and has a dismal prognosis. Our case report outlines the current approach for diagnosis and management of this rare form of acral lentiginous melanoma.

Primary Breast Lymphoma: A Rare Clinical Entity.

Localized primary breast lymphoma is very rare. The typical clinical and radiographic presentation of isolated primary breast lymphoma mimics that of breast adenocarcinoma. Histologic diagnosis of primary breast lymphoma relies heavily on Hematoxylin and Eosin pathologic evaluation and immunohistochemical staining. Cytotoxic systemic chemotherapy is the primary treatment for this disease with the occasional need for adjuvant radiation therapy or surgical resection. This case report outlines the diagnosis and management of a patient with primary breast lymphoma.

The association of plasma fatty acids with prostate cancer risk in African Americans and Africans.

Higher risk for prostate cancer (PCa) among African Americans is partly associated with exposure to dietary fatty-acids, the carcinogenic effects of which remain controversial. Odds ratio of PCa risk was determined by unconditional logistic regression comparing highest with lowest quartiles of plasma fatty-acids in a case-control design. Mean age for 173 African Americans and 340 Nigerians was 56.9 +/- 9.8 and 60.1 +/- 14.0, p<.006, median (25th, 75th percentile) plasma fatty-acid was 2598 (2306, 3035) microg/ml and 2420 (2064, 2795) microg/ml, p<.001, with 48 (27.7%) and 66 (19.4%) PCa cases, respectively. African Americans recorded higher total, omega-6, and trans, but lower saturated and omega-3 fatty-acids, with non-significant PCa risk association for total, omega-6 and trans fatty acids. Positive PCa risk trend was observed in both populations with nervonic, erucic, and arachidonic acids, with docosahexaenoic acid (DHA) among African Americans, and with behenic and stearic acids in Nigerians. Non-significant negative PCa risk trend was observed with ecosapentaenoic acid (EPA) in Nigerians only. These preliminary findings need to be further explored in a larger study that will include risk analysis of fatty-acid ratios to clarify their combined impact on PCa risk.

Sigmoid-urachal-cutaneous fistula in an adult male.

An infected urachal cyst is an uncommon finding in adults. We report the first case of a sigmoid-urachal-cutaneous fistula that resulted from rupture of an infected urachal cyst in an adult male. Definitive management consisted of resection of the urachus with a bladder cuff, along with removal of the affected bowel segments and bowel anastomosis.

Adenomatous hyperplasia of the gallbladder.

Adenomatous hyperplasia of the gallbladder is an uncommon condition, particularly in men. A literature search yields minimal information on this entity, thus suggesting the infrequency of its occurrence. Adenomyomatosis is an entity that closely resembles adenomatous hyperplasia but has hypertrophy of the muscular layer and extensive Rokitansky-Aschoff sinuses. We report the finding of adenomatous hyperplasia in a middle-aged male in the setting of symptomatic cholelithiasis.

Ageism in breast cancer surgical options by medical students.

INTRODUCTION: The similar long-term survival of breast conservation and modified radical mastectomy in treating early invasive breast cancer has been well established. Since doctors often find themselves in the position of making operative recommendations, characterization of factors that may influence their recommendations is important. Previous investigations have demonstrated the phenomenon of ageism (i.e., between patients aged 30 versus 60 years old) in doctors and doctors-in-training. Thus, this study was undertaken to investigate any possible economic bias of doctors-in-training in breast conserving procedures. METHODS: Medical students were instructed on the efficacy of breast conservation in treating breast cancer. Then, their opinions were assessed using a questionnaire about recommendations for breast conservation as well as breast reconstruction after mastectomies in similar patients. All patients were between the ages of 41-54 years old but differed by occupation. Chi squared tests were used for statistical analysis. RESULTS: Forty-eight students participated in the study. No differences were noted between "high income" occupations and "low income" occupations. However, subtle ageism was noted even in this similarly aged population. Modified radical mastectomy was recommended in 35 percent of the "older" age group (41-48 years old) versus 15 percent of "younger" patients (49-54 years old, p < 0.002). Further, breast reconstruction was recommended in 89 percent of younger patients versus only 72 percent of older patients (p < 0.004). CONCLUSIONS: Medical students still demonstrate an age bias against older women in their recommendations of breast conservation and breast reconstruction. Educational efforts should be instituted during the medical school training to decrease this age bias in treatment of breast cancer.

Paget's disease of the breast areola mimicking cutaneous melanoma.

Paget's disease of the breast nipple and areola complex represents a cutaneous manifestation of an underlying breast malignancy. The typical skin changes characteristic of breast Paget's disease are usually easily distinguished from those found of malignant melanoma. The rare finding of a pigmented cutaneous breast lesion mimicking melanoma presents a diagnostic dilemma. This case presentation describes a pigmented mammary lesion involving the areola that had undergone changes in diameter and pigmentation. The lesion was not associated with nipple drainage, nipple excoriation, dermal ulceration, or a palpable breast mass. The areola lesion was highly suggestive of a dermatologic malignancy such as malignant melanoma. As such, a biopsy was performed with initial findings suggestive of cutaneous melanoma. Upon more detailed analysis of a larger excision specimen, immunohistochemical staining was highly supportive of the diagnosis of breast Paget's disease. A total mastectomy with sentinel lymph node evaluation was performed along with immediate reconstruction. The final pathology revealed a small focus of ductal carcinoma in situ of the breast associated with the areola changes. Histologic and immunohistochemical analysis of a biopsy specimen were paramount in differentiating these two lesions.

Poor knowledge of basic cancer facts of physicians-in-training.

PURPOSE: Since many physicians-in-training will play an important role in cancer screening, their understanding of cancer screening and basic cancer facts is paramount. This investigation was undertaken to determine their baseline knowledge in basic cancer facts. METHOD: A questionnaire was used to assess the knowledge of basic cancer facts of medical students, medical residents and surgical residents. Participants were asked to rank five different malignancies in their correct order for both mortality and incidence. Physicians-in-training were given separate questions for male and female patients. The questions were considered correct if at least the first three malignancies were ranked in the appropriate order. RESULTS: One-hundred-twelve second-year medical students and 78 residents were assessed. Few physicians-in-training ranked the malignancies in correct order for mortality (21% for female patients and 18% for male patients). Even fewer physicians-in-training ranked the malignancies in correct order for incidence (2% for female patients and 9% for male patients). CONCLUSION: Most physicians-in-training lack an understanding of basic cancer facts. If this poor basic cancer fact knowledge represents an overall lack of cancer knowledge, educational efforts need to be focused on cancer care for all levels and specialties of physician training.

Laparoscopic revision of the gastrojejunostomy for recurrent bleeding ulcers after past open revision gastric bypass.

Late complications of open gastric bypass can include malnutrition, weight gain, stomal stenosis, and recurrent bleeding ulcers. Herein, we describe the case of a woman who had recurrent bleeding ulcers, after an open revision of a stenotic gastric bypass. She now underwent an uneventful laparoscopic revision of her gastrojejunostomy and was discharged within 72 hours. Laparoscopic revision of a gastrojejunostomy, even after an open revision following an open gastric bypass, can be done safely.

Multivariate analysis of factors associated with smoking cessation in women.

BACKGROUND: Appropriate smoking cessation techniques, including counseling patients to stop smoking, could prevent multiple health-related problems. Identification of relevant factors in patients that smoke may be beneficial in targeting smoking cessation efforts. This investigation explores various factors associated with smoking cessation, specifically in women. METHODS: All women (n = 675) presenting to a breast health center over a one year period were surveyed regarding their tobacco use. Any association between smoking cessation and various factors was determined by multivariate analysis. RESULTS: Our population consisted of 47% African American women, 43% Caucasian women, and 10% women of other ethnicities. Sixty percent of all women never smoked. Of the women who had smoked, 57% quit. Except for alcohol use and exercise, no factor, including ethnicity, was associated with never smoking. Smoking cessation was associated with being married, being Caucasian, not using alcohol, and exercising. However, only Caucasian race and marriage were independently associated with smoking cessation. DISCUSSION: In our population, African American women had a lower proportion of smoking cessation than Caucasian women. In patients with similar access to care, specifically preventive care, there are ethnic and social differences in smoking cessation.

Dermatofibrosarcoma protuberans and breast cancer: genetic link or coincidental association?

Dermatofibrosarcoma protuberans is a low-grade cutaneous neoplasm originating from the dermis with a high propensity for local recurrence. These malignancies are classified as soft tissue sarcoma although regional or distance metastatic spread is rare. Germ-line mutations of p53 have been described with a rare autosomal dominant syndrome in patients with soft tissue sarcoma and breast adenocarcinoma (Li Fraumeni's syndrome). The described case illustrates the rare occurrence of dermatofibrosarcoma protuberans (DFSP) and breast adenocarcinoma with an emphasis on the possibility of a molecular or genetic association.

Nodular melanoma of the face: a rare finding in African Americans.

The incidence of melanoma has dramatically increased during the past several decades in the United States. Although the majority of cutaneous melanomas occur in Caucasians, African Americans are also susceptible to this malignancy. Cutaneous melanomas in African Americans typically occur on palms of the hands or soles of the feet. This report documents the rare occurrence of a nodular melanoma of the face in a dark-complexion African-American patient.

Physicians-in-training recommendations for prophylactic bilateral mastectomies.

The decision to recommend bilateral prophylactic mastectomy (PBM), one treatment modality used to reduce the development of breast carcinoma, may be influenced by physician bias. This investigation tested the hypothesis that there are physician-in-training biases in recommendations of PBM. All second-year medical students, general surgical residents, and internal medicine residents at our institution participated in a survey in which they were asked at what percent risk of developing breast carcinoma the physicians-in-training would recommend PBM for 1) their patients, 2) themselves, and 3) their significant others, as applicable. A total of 198 physicians-in-training responded. Univariate analysis demonstrated an association between both the type of physician-in-training (p<0.03) and gender (p<0.004) with the percent risk for which respondents would recommend PBM. However, with multivariate analysis, only gender was associated with percent risk (p<0.05). Physicians-in-training also chose PBM at a lower risk for their significant others than for themselves (67.5% versus 57.2%; p<0.02). Respondents also chose PBM at a similar risk for themselves or significant others as for their patients (r=0.83, r=0.98; p<0.001). This investigation suggests that males (compared to females) are more likely to recommend PBM for the prevention of breast cancer.

Effect of a short structured session on medical student breast cancer screening knowledge.

Formalized instruction in breast cancer screening during medical school may help improve early breast cancer detection and survival. Physicians-in-training must be proficient in skills relating to breast cancer screening. This study investigates the baseline breast cancer screening knowledge of medical students, the benefit of a structured lecture session, and its effect on improving medical students' knowledge of cancer screening. A self-administrated questionnaire relating to breast cancer screening was given to third-year medical students. A 60-minute structured lecture session was given to the medical students regarding breast cancer screening. A postintervention survey was administered immediately following the session. A total of 27 medical students were evaluated. There was a statistically significant improvement following the formalized teaching session (84% to 93%; p < 0.0016). While few students (15%) reported having previous instruction in cancer screening, most students (96%) felt that a formal session should be offered during medical school. While medical student knowledge of breast cancer screening may be adequate, formalized instruction in breast cancer health practices can improve medical student knowledge. Most students had limited previous instruction in breast cancer prevention and welcomed the opportunity for structured training in breast cancer prevention, education, and detection. Until a formal course becomes a fundamental aspect of medical education, a short structured session should be instituted.

Human immunodeficiency syndrome and hepatitis B and C infections among homeless adolescents.

The lifestyle of homeless adolescents places them at high risk for contracting a variety of serious illnesses. The purpose of this cross-sectional study was to determine the predictors of human immunodeficiency virus (HIV) and hepatitis infections among homeless youth. Anonymous and confidential interviewer-administered psychosocial surveys were conducted with 150 homeless youth (ages 14 to 23 years; 70% male). Venous blood samples were collected as well. Most respondents (95%) had engaged in sexual intercourse, with 13 years as the median age at first coitus. Approximately 36 percent indicated they had exchanged sex for food, shelter, or drugs. Although youth reported a high rate of consistent condom use, 16 percent of the sample tested positive for HIV, 17 percent tested positive for hepatitis B (HBV), and 12 percent tested positive for hepatitis C (HCV). Homeless youth should be considered a high-risk group for contracting HIV, HBV, and HCV infections. The positive rates for HIV, HBV, and HCV observed in this study are higher than those of many previous reports among street youth. Because HIV prevention and hepatitis B vaccination programs have been targeted at school-based youth, most homeless youth are missed by these efforts. Targeted programs are needed to reach this high-risk group. Suggested guidelines for clinicians involved in the provision of medical care to homeless children and adolescents are provided.