A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Prevalence of Complementary and Alternative Medicine in Immigrants

Immigrants face barriers to accessing conventional health care systems. Hence, they are expected to have comparatively greater use of complementary and alternative medicine (CAM). This study examines the prevalence of and reason for CAM use in the U.S. population by citizenship status. Data on 34,483 U.S.-born, naturalized, and non-U.S. citizens from the 2012 National Health Interview Survey was used. CAM was categorized into four domains. Analyses controlling for socioeconomic variables were identified patterns of utilization and reasons for use. The prevalence of all CAM domains was lowest among non-U.S. citizens followed by naturalized citizens. The odds of using CAM were also higher for the immigrants who attained citizenship than for non-citizens. Individuals in all groups reported using more CAM for prevention. Factors related to cost, accessibility, or knowledge of CAM use may contribute to lower use of CAM by naturalized and non-U.S. citizens.     

A Survey of Physicians' Attitudes and Practices about the Human Papillomavirus (HPV) Vaccine in Hawai‘i

The human papillomavirus (HPV) vaccine has the potential to decrease the incidence of several cancers that affect women and men. Despite recommendations by the medical and public health community, and the incorporation of the vaccine into the adolescent immunization schedule, uptake of the vaccine remains well below target goals. To understand potential physician barriers to recommendation and provision of the vaccine, a cross-sectional survey was administered to Hawai‘i pediatricians and family physicians from July 2012 to September 2012 on their attitudes, practices, and perceived barriers regarding HPV vaccination. Surveys were mailed to 465 members of the local pediatrics and family medicine professional chapters, and 87 responses were received for a response rate of 19%. After excluding 14 responses, 73 surveys were included in the analysis. Although almost all of the respondents reported stocking and administering the HPV vaccine in their offices, only 71% reported strongly recommending the HPV vaccine to girls 11–12 years, and only 57% strongly recommend the vaccine to boys 11–12 years old. Lack of insurance coverage and other financial considerations were barriers to provision of the vaccine by physicians. Physicians who felt it is necessary to discuss sexuality with patients prior to recommending the vaccine were significantly less likely to strongly recommend the vaccine to boys 11–12 years old. Public health efforts should focus on addressing the financial barriers and encouraging physicians to recommend the HPV vaccine according to the guidelines.     

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.     

Preoperative Chemotherapy Does Not Adversely Affect Pancreatic Structure and Short-Term Outcome after Pancreatectomy

Background

Preoperative chemotherapy (PCHT) has recently been proposed also in patients with resectable pancreatic adenocarcinoma. Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection. The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection.

Methods

Fifty consecutive patients successfully underwent resection after PCHT. Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospective electronic database. Match criteria were age (±3 years), gender, American Society of Anesthesiologist score, type of resection, pancreatic duct diameter (±1 mm), and tumor size (±5 mm). Primary endpoint was morbidity rate. Secondary endpoints were pancreatic parenchymal structure, mortality rate, and length of hospital stay (LOS).

Results

Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups. Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group (p?=?0.37). Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group (p?=?0.41). Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group (p?=?0.60). Mean LOS (days) was 12.7 in the PCHT group vs. 12.4 in the control group (p?=?0.74). There was no difference in resection margin status, while the rate of patients without nodal involvement was higher in the PCHT group (46.0 vs. 23.0 %, p?=?0.004).

Conclusion

PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery.     

Proposal for a New Pathologic Prognostic Index After Neoadjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma (PINC)

Background

Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology.

Patients and Methods

The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index.

Results

The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model.

Conclusions

The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.

     

Multidrug regimens for treatment of older patients with metastatic pancreatic cancer

Background and AimsOlder patients with metastatic pancreatic adenocarcinoma (MPDAC) are under-represented in clinical trials.MethodsOur single-center, retrospective study enrolled MPDAC patients ≥ 70 treated with chemotherapyResults105 patients were divided in groups based on the received treatments: 44 gemcitabine or capecitabine monotherapy (A), 34 nabpaclitaxel-gemcitabine (B) 27 4-drugs combinations (gemcitabine, cisplatin, capecitabine plus either nab-paclitaxel or epirubicin or docetaxel) (C). Group A: median age was 78 (70–87) and Karnofsky performance status (KPS) ≥80 was found in 84% of patients; Group B: median age 77 (71–84) and KPS ≥ 80 in 88% of patients; Group C: median age 73 (70–78) and KPS ≥ 80 in 93% of patients. Median OS was 7.9, 11.7 and 14.2 months in group A, B and C respectively; 1 and 2-year OS were 27% and 8% in group A; 44% and 5% in group B; 52% and 22% in group C. When lung metastatic only patients were excluded, patients <75 and ≥ 75 had similar OS in group A (6.4 vs 5.6 months) and in group B (12.3 vs 11.1 months). In group B grade 3 thrombocytopenia, fatigue and peripheral neuropathy were more frequent in patients ≥ 75.ConclusionsIn older patients, combination chemotherapy shows acceptable feasibility and promising efficacy.     

Predisposing factors,clinical presentation and outcome of treatment of avulsive human bites on the face: a case series analysis from Abuja,Nigeria

Background

Human bite can be classified as occlusive or non-occlusive. Occlusive bites are seldom reported to occur outside the facial region. This study aims to analyze cases of avulsive human bite and find which part of the face is the most frequently involved in such cases. The findings may indicate which part of the face is generally perceived as the most critical in judging attractiveness.

Methods

This retrospective study was carried out using a data review of all consecutive avulsive facial human bite cases seen in the maxillofacial surgery unit, National Hospital Abuja, between February 2001 and January 2014. Uniform protocol of prophylactic oral antibiotic and anti-tetanus cover was ensured throughout the study period.

Results

Seventeen cases were included in this study. Amorous jealousy was the cause of altercation in 15 (88.2 %) cases. Twelve (70.6 %) cases involved the lip. There were eight female and nine male victims. There were nine female and eight male assailants.

Conclusions

The lip is the most frequently affected region of the face in avulsive human bite attacks in our environment. This may be because it is considered the most important anatomical region of the face on which judgment of attractiveness is based. Level of evidence: Level IV, prognostic/risk study.