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.

Implementing the Prospective Surveillance Model (PSM) of Rehabilitation for Breast Cancer Patients with 1-Year Postoperative Follow-up, a Prospective, Observational Study.

BACKGROUND: The Prospective Surveillance Model (PSM) of rehabilitation for patients with breast cancer aims for early identification, treatment, and support of physical impairments postoperatively. The purpose of this study was to describe the incidence of impairments during the first postoperative year and the differences between the patients requiring rehabilitation intervention versus those not requiring intervention. METHODS: A total of 120 patients were enrolled. Impairment measures included: pain, range of motion, and self-reported measures of function using the Upper Extremity Functional Index (UEFI) and Quick Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaires. These measures were performed at designated intervals during the first postoperative year. All patients received exercise and education, and patients with identified impairments underwent individualized rehabilitation intervention. Clinical factors associated with need for intervention were determined using univariate analysis. RESULTS: Thirty-six patients required rehabilitation intervention. There were no statistically significant differences between intervention and no-intervention groups for body mass index, breast surgery type, reconstruction type, or radiotherapy. Statistically significant differences were found between intervention and no-intervention groups in early postoperative UEFI, QuickDASH, pain scores, age, number of lymph nodes removed [9.3 (intervention) vs. 5.6 (no-intervention)], axillary surgery type, chemotherapy, and breast cancer stage. CONCLUSIONS: Survivorship practitioners should have heightened awareness for rehabilitation intervention in patients with greater axillary surgery and burden of disease. Patients with more activity restriction and lower levels of function in the early postoperative period may benefit from rehabilitation intervention. Future studies should focus on implementing a screening tool to identify patients in need of rehabilitation referral.

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.

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.

Incarcerated Spigelian hernia: a rare cause of mechanical small-bowel obstruction.

Spigelian hernias are rare abdominal wall defects that occur at the semilunar line lateral to the rectus abdominis muscle. The majority of patients present with symptomatic incarceration of preperitoneal fat or intra-abdominal viscera. Radiographic studies are beneficial in confirming the diagnosis. The high rate of incarceration with or without strangulation mandates operative repair once the diagnosis is confirmed. This manuscript outlines the clinical presentation and management of a patient with an incarcerated Spigelian hernia.

The association of plasma fatty acids with prostate cancer risk in Nigerians.

PURPOSE: To investigate the role of fatty acids (FAs) in prostate cancer (PCa) risk in Nigeria, a country in transition to westernized diet high in animal fats, and currently experiencing rising rates of prostate cancer. METHODS: Men > or =40 years were recruited from surgery/urology clinics, University of Benin Teaching Hospital and from 2 rural and 2 urban communities. Personal information, urological symptom history and anthropometrics were recorded, digital rectal examination performed, and 30 mLs of fasting blood collected for prostatic specific antigen and fatty acid (FA) analysis. Odds ratio (OR) of PCa risk was determined by unconditional logistic regression with the plasma FA 1st quartile as reference, controlling for age, education, waist-to-hip ratio, and family history. RESULTS: Mean ages for 66 (22.6%) cases and 226 (77.4%) controls were 71.9+/-11.47 and 56.7+/-12.69 years, P<.001, and median (25th, 75th percentile) fasting plasma FA were 2,447 (2,087, 3,024) and 2,373 (2,014, 2,751) microg/mL, respectively. PCa risk trend was observed for total omega-6 FA, adjusted ORQ3vs.Q1 2.33 (95% CI, 0.77-7.07), P<0.05. Unadjusted ORQ4vs.Q1 for behenic and nervonic acids were 2.79 (95% CI, 1.27-6.10) and 2.40 (95% CI, 1.19-4.85), and unadjusted ORQ2vs.Q1 for erucic and arachidonic acids were 4.20 (95% CI, 1.79-9.82) and 3.81 (95% CI, 1.50-9.70) respectively. Unadjusted ORQ2vs.Q1 for omega-3 FAs eicosapentaenoic (EPA) and docosapentaenoic (DPA) were 0.39 (95% CI, 0.18-0.85) and 0.79 (95% CI, 0.35-1.79) respectively. CONCLUSIONS: In this population with high total plasma omega-3, we observed modest positive PCa risk trend with total plasma omega-6 (2.3), inverse risk reduction with EPA (0.4), and strong positive risk associations with behenic (2.8), erucic (4.2), and nervonic (2.4) acids. Total plasma omega-6 is highest in the educated high-income group. These findings should be confirmed in a larger study because of the potential serious implication of dietary transition particularly in a region designated as low-incidence for PCa.

Dental impression material: a rare cause of small-bowel obstruction.

Small-bowel obstruction due to foreign bodies is unusual in adults. Intestinal obstruction is occasionally caused by pits, bezoars, endoscopy capsules, and gastrostomy tube buttons. We report a rare case of distal small-bowel obstruction due to dental impression material. Avoidance of this potentially life-threatening complication may be achieved by increased vigilance in accounting for all impression material when dental impression trays are removed. Early detection of swallowed dental material may afford endoscopic removal from the stomach, thus preventing intestinal obstruction.

Cancer in the bypassed stomach presenting early after gastric bypass.

Gastric carcinoma in the bypassed stomach after Roux-en-Y gastric bypass (RYGBP) is rare but has been reported. The time from RYGBP to the presentation of cancer has ranged from 5 to 22 years postoperatively in the literature. A major concern with the current technique for RYGBP is the exclusion of the bypassed stomach and difficulty in surveillance. Thus, some surgeons recommend routine preoperative evaluation via endoscopy. Although most findings are benign, abnormalities are frequently discovered during screening endoscopy in bariatric surgery patients. We present a 45-year-old woman who was discovered to have disseminated gastric cancer involving the excluded bypassed stomach following an open RYGBP. Preoperative upper endoscopy was not performed. This case illustrates the importance of endoscopic evaluation prior to RYGBP and signifies the need for a high index of suspicion in order to recognize this problem at an early stage.

Foreign body ingestion and management: "I swallowed a crack pipe".

There is a wide variety of objects that find their way into the human gastrointestinal tract, either accidentally or deliberately. In this case a crack pipe was ingested in its entirety. Despite the seemingly rare and random nature that this scenario presents, this patient's care serves to reinforce what should be done to successfully manage a patient with an ingested foreign body, as well as the important issues related to crack cocaine abuse.

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.

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.

Hospital-based, Multidisciplinary, youth mentoring and medical exposure program positively influences and reinforces health care career choice: "The Reach One Each One Program early Experience".

BACKGROUND: According to the National Center for Educational Statistics, underrepresented minorities (URMs) are more likely to leave science, technology, engineering and mathematics (STEM) fields at higher rates than their peers during undergraduate studies. Many institutions of higher learning have implemented pipeline programs aimed at preparing and inspiring high school and college aged students in select careers in health sciences with varying levels of success. Research has shown that a health care workforce that mirrors the community they serve is more effective in reducing health disparities and increasing positive health outcomes. We hypothesize that a hospital-based, multidisciplinary youth mentoring and medical exposure program will enhance the decision of URM high school students to choose healthcare careers. MATERIALS AND METHOD: A retrospective analysis of the Reach One Each One Program (ROEO) was performed. ROEO is a hospital based, 11-week multidisciplinary youth mentoring and medical exposure program for inner-city high school students. The analysis was based on a phone survey of the twenty-six (26) seniors who completed the program and subsequently graduated from high school between May 2013 and May 2015 to assess the following: 1) College enrollment/attendance, 2) Health profession majors, and 3) Pre-med status. The study was approved by the Morehouse School of Medicine Institutional Review Board. RESULTS: Of the twenty-six students, 23 were female and 3 were male; 25 (96%) of the students were African American and one student was a Caucasian female. Twenty-four (92.3%) of the students were enrolled in college and 2 (7.7%) were scheduled to begin in the spring semester of 2016. Twenty-one of the 24 attending college at the time of the survey (87.5%) were enrolled in a health science degree program and 16 (66.7%) confirmed that they were enrolled in pre-medical (Pre-med) curriculum. CONCLUSION: Hospital-based, multidisciplinary medical mentoring programs can have a positive impact on the lives and health care career decisions of aspiring URM high school students. Further study will be necessary to validate the most influential components needed for the success of such programs.

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.

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.

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.

Laparoscopy shortens length of stay in patients with gastric electrical stimulators.

BACKGROUND: Gastric electrical stimulation has been proven effective for drug-refractory gastroparesis. Placement of stimulator leads and device usually requires a laparotomy, although laparoscopic placement has also been used. METHODS: To compare laparotomy with laparoscopy, we examined 36 patients, 18 undergoing laparoscopy and 18 undergoing laparotomy, matched for primary diagnosis and health resource usage. We compared baseline symptoms, length of surgery, length of postoperative hospital stay, gastric emptying, and health resources in each of the 2 groups over time, to see what variables, if any, differed. RESULTS: Baseline symptoms, gastric emptying, and health resource usage were similar. Operative times were also similar, but length of stay declined from a mean of 6.4 days for laparotomy to 1.1 days for laparoscopy. Long-term outcome, via symptoms, gastric emptying, and health resource utilization were comparable between the 2 groups. CONCLUSION: Laparoscopic placement of gastric electrical stimulator leads and device is associated with shorter lengths of postoperative hospital stay. However, the patients who underwent laparotomy had higher vomiting scores and more previous abdominal surgeries at baseline, and higher long-term mortality at follow-up, suggesting that they may be more ill, as a group, than the laparoscopic patients. Laparoscopic placement of devices may be preferable when technically feasible.

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.

Insulin-like growth factor-I receptor activation blocks doxorubicin cytotoxicity in sarcoma cells.

More than 80% of patients with extremity sarcoma ultimately develop metastases to pulmonary sites. Doxorubicin alone or in combination with other chemotherapeutic agents may result in partial or complete tumor response for sarcoma pulmonary metastases. Regardless of the response, there has been no proven survival benefit from cytotoxic chemotherapy in the treatment of localized or metastatic soft tissue sarcoma. Insulin-like growth factor-I receptor (IGF-I-R) activation may contribute to resistance to chemotherapy in mesenchymal neoplasia. IGF-I-R activation by its ligand decreases in vitro cytotoxic response of sarcoma to doxorubicin, the most active agent against soft tissue sarcoma in adults. Furthermore, IGF-I-R is frequently overexpressed in soft tissue sarcoma and may predict poor response to traditional chemotherapy. The effect of doxorubicin on a human soft tissue sarcoma cell derived from a dedifferentiated lung metastasis was evaluated using titrated doxorubicin doses with and without exogenous IGF-I (100 ng/ml). Western blot analysis was performed to evaluate levels of phosphorylated IGF-I-R under control and experimental conditions. In vitro proliferation assays were performed. Nuclear activation through IGF-I receptor mediated pathways prior to exposing sarcoma cells to doxorubicin altered the pattern of response to doxorubicin with enhanced mitogenesis (>2-fold) and blunted doxorubicin cytotoxicity (>10% change in IC50). These data suggest that activation of IGF-I receptor in sarcoma cells is a potential mechanism for tumor resistance to doxorubicin. Inhibition of IGF-I receptor activation represents a novel approach to enhance the degree and duration of response to traditional chemotherapy against soft tissue sarcoma.

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.