[First outpatient satisfaction questionnaire with day-surgery in a French comprehensive cancer center].

[First outpatient satisfaction questionnaire with day-surgery in a French comprehensive cancer center].

Bull Cancer. 2016 Feb 24;

Authors: Gaujal L, Renou M, Dujaric ME, Baffert S, Tardivon A, Kriegel I, Buecher B, Girod A, Grosset L, Asselain B, Rouzier R, Brédart A, Alran S

Abstract
INTRODUCTION: To assess the patient's satisfaction in a day-surgery unit in oncology for a surgical diagnosis or therapeutic act.
METHODS: Between October 2013 and February 2014, we conducted a satisfaction survey from the validated questionnaire COPS-D. This questionnaire analyse the patient's stages in the care system, from the preoperative consultation to the return home: 9 stages with 23 items rated 1 (bad) to 5 (excellent). It was sent by postmail 3 weeks after their hospitalization.
RESULTS: Four hundred and sixty-seven questionnaires were mailed, with a response's rate to 38% (172/467). Participant's characteristics: 88% are women, 45% are full time workers, 54% of senology. Two-third of the assessments were rated 4 or 5. Five percent were rated 1 or 2. The patient's exit is the least preferred step. The operating room's assessment is the most preferred by patients. Sixty-one percent of participants have written a free comment, 31% are positives, 36% are negatives, and 32% are mixed. The wait was the negative recurrent comment (21%).
DISCUSSION: Most participants are very satisfied. Improving the wait before the operation and output is already underway. Studies are now needed to assess the care's safety and the economic aspect of day-surgery.

PMID: 26922667 [PubMed - as supplied by publisher]

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[Medical management of cholangiocarcinomas in 2015].

[Medical management of cholangiocarcinomas in 2015].

Bull Cancer. 2016 Feb 24;

Authors: Marret G, Neuzillet C, Rousseau B, Tournigand C

Abstract
Cholangiocarcinoma is a rare malignancy carrying a poor prognosis. Most patients are diagnosed with advanced-stage disease and are then ineligible for surgical resection, which is the only potentially curative therapeutic modality. The aim of this article is to provide an up-to-date review of medical management of patients with cholangiocarcinoma. The benefit of adjuvant therapy in patients undergoing curative-intent surgery is under evaluation. Combination chemotherapy with gemcitabine and platinum is the standard first-line treatment for patients with advanced cholangiocarcinoma. Targeted agents are not currently recommended due to limited data on use in this setting. The role of second-line chemotherapy is not established in advanced cholangiocarcinoma. Identification of predictive and prognostic markers to select patients who could benefit from second-line therapy is a major issue. A better understanding of the biological and molecular mechanisms underlying the carcinogenesis and the phenotypic heterogeneity of cholangiocarcinoma may path the way of new therapeutic strategies.

PMID: 26922666 [PubMed - as supplied by publisher]

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Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers

Abstract

Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994–2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori-related) and gastric ulcers (dominantly lifestyle-related) compared with the general population. We started follow-up 1-year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1–5-year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31–1.44) and 1.30 (95% CI: 1.23–1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking- and alcohol-related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized.

Patients with gastric ulcer and duodenal ulcer have an increased risk of all gastrointestinal cancers, compared with the general population. Site-specific absolute cancer risks were similarly low in both Peptic ulcer disease (PUD) cohorts, and the direction of the associations with both gastric and other GI cancers was consistent among patients with the two ulcer types.

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EphA4-deleted microenvironment regulates cancer development and leukemoid reaction of the isografted 4T1 murine breast cancer via reduction of an IGF1 signal

Abstract

EphA4 belongs to the largest family of receptor tyrosine kinases (RTKs). Although EphA4 is highly expressed in the central nervous system, EphA4 has also been implicated in cancer progression. Most of the studies focus on the expression and function in tumor cells. It is unknown whether EphA4-deleted microenvironment affects tumor progression. Some of cancers in animals and humans, such as 4T1 cancer cells, are known to produce a large amount of granulocyte colony-stimulating factors (G-CSF/Csf3) which can stimulate myeloproliferation, such as myeloid-derived suppressor cells (MDSCs) leading to a poor recipient prognosis. We isografted 4T1 breast cancer cells into both EphA4-knockout and control wild-type female littermate mice. The results showed that the EphA4-deleted host could inhibit primary tumor growth and tumor metastasis mainly by decreasing the amount of IGF1 synthesis in the circulation and locally tissues. The EphA4-deleted microenvironment and delayed tumor development reduced the production of G-CSF resulting in the decrease of splenomegaly and leukemoid reaction including MDSCs, which in turn inhibit the tumor progression. This inhibition can be reversed by supplying the mice with IGF1. However, an excess of IGF1 supply over demand to the control mice could not further accelerate the tumor growth and metastasis. A better understanding and re-evaluation of the main role of IGF1 in regulating tumor progression could further enhance our cognition of the tumor development niche. Our findings demonstrated that EphA4-deleted microenvironment impairs tumor-supporting conditions. Conclusion: Host EphA4 expression regulates cancer development mainly via EphA4-mediated IGF1 synthesis signal. Thus, targeting this signaling pathway may provide a potential therapeutic option for cancer treatment.

Host EphA4 expression regulates cancer development mainly via EphA4-mediated IGF1 synthesis signal. Thus, targeting this signaling pathway may provide a potential therapeutic option for cancer treatment.

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Laparoscopic surgery for patients with colorectal cancer produces better short-term outcomes with similar survival outcomes in elderly patients compared to open surgery

Abstract

The number of operations on elderly colorectal cancer (CRC) patients has increased with the aging of the population. The aim of this study was to evaluate surgical outcomes in elderly patients who underwent laparoscopic or open surgery for CRC. We analyzed the data of 280 patients aged 80 or over who underwent surgery for CRC between January 2001 and December 2010. Seventy-one pairs were selected after propensity score matching for laparoscopic or open surgery. Operative time, return to normal bowel function, length of hospital stay, postoperative complications, overall survival (OS), recurrence-free survival (RFS), and prognostic factors affecting survival were investigated. In matched cohorts, operative time in the laparoscopic group was longer than in the open group (P < 0.001). In the laparoscopic group, time to flatus passage (P < 0.001) and length of postoperative hospital stay (P = 0.037) were shorter than in the open group. The rate of operation-related morbidity was higher in the open group (P = 0.019). There was no difference in OS and RFS between two groups. This study suggests that laparoscopic surgery for CRC in elderly patients may be safe and feasible, with better short-term outcomes. OS and RFS, however, were not different in both groups.

In this study, laparoscopic colorectal surgery in elderly patients achieved better results than open surgery in terms of bowel function recovery, length of hospital stay, and postoperative complications. Overall survival and recurrence-free survival following laparoscopic and open colorectal resections were similar in the elderly population. These findings indicate that laparoscopic colorectal surgery in elderly patients is safe and feasible, and should be considered as a treatment option.

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Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database—Breast Cancer Registry

Abstract

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed-up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m²) categories; <18.5 (underweight), ≥18.5–<21.8 (reference), ≥21.8–<25, ≥25–<30 (overweight), and ≥30 (obese). We divided normal weight patients into two subgroups because this category includes many patients compared to others. The timing of BMI measurement was not specified. The Cox proportional hazards model and cubic spline regression were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking, alcohol, and physical activity were not controlled. A total of 1418 all-cause, 937 breast cancer–specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all-cause (HR: 1.46; 95% CI: 1.16–1.83) and breast cancer–specific death (HR: 1.47; 95% CI: 1.11–1.93) for all patients, and with all-cause (HR: 1.47; 95% CI: 1.13–1.92) and breast cancer–specific death (HR: 1.58; 95% CI: 1.13–2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all-cause death for all (HR: 1.41; 95% CI: 1.16–1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15–1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer–specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51–4.43; P_{heterogeneity} of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71–6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

Few studies have reported the association between body mass index and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed up for a median period of 6.7 years (119,873.4 person years) entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. The timing of body mass index (BMI) measurement was not specified. Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

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MiR-24 enhances radiosensitivity in nasopharyngeal carcinoma by targeting SP1

Abstract

Radioresistance remains a major problem in the treatment of patients suffering from nasopharyngeal carcinoma (NPC). A better understanding of the mechanisms of radioresistance may generate new strategies to improve NPC patients' responses to therapy. This study was designed to investigate the effect of microRNA on the radiosensitivity of NPC cells. A microRNA microarray indicated that miR-24 was downregulated in NPC cell lines and tissues. Furthermore, cell proliferation was suppressed and radiosensitivity increased when miR-24 was ectopically expressed in NPC cells. Specificity protein 1 (SP1) was additionally verified as a direct functional target of miR-24, which was found to be involved in cell viability as well as the radiosensitivity of NPC cells. In conclusion, the results of this study suggest that the miR-24/SP1 pathway contributed to the reduction in radioresistance in human NPC and that it may thus represent a therapeutic target.

This study aimed to investigate the effect of microRNA (miR)-24 on the radiosensitivity of NPC cells. The results of this study suggested that the identified miR-24/Sp1 pathway contributed to the elucidation of the mechanisms of radiosensitivity in human NPC and that it may represent a potential therapeutic target.

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The prognostic significance of monoclonal immunoglobulin gene rearrangement in conjunction with histologic B-cell aggregates in the bone marrow of patients with diffuse large B-cell lymphoma

Abstract

Bone marrow involvement (BMI) is a well-known poor prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL). This study robustly investigated the significance of monoclonal immunoglobulin gene rearrangement combined with histologic B-cell aggregates in bone marrow (BM) in the detection of a poor prognostic group. Pretreatment BM samples of 394 DLBCL patients were analyzed via the immunoglobulin gene rearrangement study and the microscopic examination. Monoclonal immunoglobulin gene rearrangement was detected in 25.4% of cases. Histologic B-cell aggregates with the features of large B-cell lymphoma aggregates, small cell B-cell lymphoma aggregates, or B-cell aggregates of unknown biological potential were observed in 12% of cases (6.9%, 1.3%, and 3.8%, respectively). Histologic B-cell aggregates were more associated with monoclonality than polyclonality. Cases with both monoclonality and histologic B-cell aggregates demonstrated close association with poor prognostic factors such as a higher International Prognostic Index score and showed an inferior overall survival rate when compared to cases with only monoclonality or only histologic B-cell aggregates. From the findings, a combination of monoclonality and histologic B-cell aggregates within the bone marrow was highly associated with poor prognosis and could be used to determine high-risk DLBLC patients with greater sensitivity and specificity than conventional microscopic examination or immunoglobulin gene rearrangement study alone.

Histologic B-cell aggregates were more associated with monoclonality than polyclonality. A combination of monoclonality and histologic B-cell aggregates within the bone marrow was highly associated with poor prognosis and could be used to determine high-risk DLBLC patients with greater sensitivity and specificity than conventional microscopic examination or immunoglobulin gene rearrangement study alone.

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Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories

Abstract

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6–6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0–9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.

Our findings suggest that men with glucose in the diabetic range are more likely to have lower PSA levels, but higher grade or advanced PCa. Conversely, men with glucose in the prediabetic range and those with hypertriglyceridemia tended to have higher PSA levels as well as higher grade or more advanced PCa.

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Recreational physical activity and ovarian cancer risk in African American women

Abstract

The literature on recreational physical activity (RPA) and ovarian cancer risk is inconclusive and most studies of RPA and ovarian cancer have been conducted in white populations. This study is the first to investigate the association between RPA and ovarian cancer in an exclusively African American (AA) population. We analyzed data from an ongoing U.S. population-based, case–control study of AA women, which included 393 women recently diagnosed with invasive epithelial ovarian cancer (IEOC) and 611 controls. A baseline interview assessed RPA frequency, intensity, and duration. Each RPA intensity was assigned a metabolic equivalent of task (MET) value and MET-min/week were calculated. Unconditional multivariable logistic regression was performed to investigate associations between RPA and IEOC risk. Compared with sedentary women, predominantly mild intensity RPA was significantly inversely associated with IEOC risk for women reporting above median (>297) MET-min/week (odds ratio [OR] = 0.52; 95% confidence interval [CI]: 0.34, 0.78) and nonsignificantly for <297 MET-min/week (OR = 0.71; 95% CI: 0.44, 1.12). Predominantly moderate intensity RPA was associated with significantly increased risk for women reporting above median (>540) MET-min/week (OR = 1.51; 95% CI: 1.03, 2.23). Predominantly strenuous intensity RPA was nonsignificantly associated with lower IEOC risk for women reporting above median (>1800) MET-min/week (OR = 0.72; 95% CI: 0.33, 1.57). The inverse associations for mild and strenuous intensity RPA were most pronounced in obese women (body mass index >30 kg/m²). The findings that mild and strenuous RPA may reduce the risk of IEOC particularly among obese women are difficult to reconcile with the increased risk observed for moderate RPA. Further research is warranted to determine whether these findings are genuine and, if so, their mechanistic basis.

This is the first study of recreational physical activity (RPA) and ovarian cancer in an exclusively African American population, who have a higher prevalence of obesity and poorer ovarian cancer survival compared with whites. We found that mild and strenuous intensity RPA may be associated with reduced ovarian cancer risk. Further, our data suggest that these associations may be more pronounced in obese women.

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Physical activity in Black breast cancer survivors: implications for quality of life and mood at baseline and 6-month follow-up

Abstract

Background

The present study sought to examine the influence of physical activity on quality of life and negative mood in a sample of Black breast cancer survivors to determine if physical activity (dichotomized) predicted mean differences in negative mood and quality of life in this population.

Methods

Study participants include 114 women diagnosed with breast cancer (any stage of disease, any type of breast cancer) recruited to participate in an adaptive cognitive–behavioral stress management intervention. The mean body mass index of the sample at baseline was 31.39 (standard deviation = 7.17).

Results

A multivariate analysis of covariance (MANCOVA) was conducted to determine if baseline physical activity predicted mean differences in negative mood and quality of life at baseline and at follow ups while controlling for relevant covariates. A one-way MANCOVA revealed a significant multivariate effect by physical activity group for the combined dependent variables at Time 2 (post 10-week intervention), p = .039. The second one-way MANCOVA revealed a significant multivariate effect at Time 3 (6 months after Time 2), p = .034. Specifically, Black breast cancer survivors who engaged in physical activity experienced significantly lower negative mood and higher social/family well-being at Time 2 and higher spiritual and functional well-being at Times 2 and 3.

Conclusions

Results show that baseline physical activity served protective functions for breast cancer survivors over time. Developing culturally relevant physical activity interventions specifically for Black breast cancer survivors may prove vital to improving quality of life and mood in this population. Copyright © 2016 John Wiley & Sons, Ltd.

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Meckel’s diverticulum complicated with gastro-intestinal stromal tumor: Case report

Publication date: Available online 27 February 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Islam H. Metwally, Amr F. Elalfy, Shadi Awny, Nirmeen Megahed
IntroductionMeckel's diverticulum is a common congenital anomaly, mostly asymptomatic. Tumors may arise rarely in these diverticulae. We claim presenting a new problem to the medical staff in Egypt.Case presentationWe report a case of a 49year old male patient who attended our center with pelvic mass insinuated between the bladder and the rectum. On exploration the mass was found arising at the tip of a Meckel's diverticulum, Gastro-intestinal stromal tumor (GIST) was confirmed by pathology.DiscussionIn review of recently published cases most of these tumors were presented with vague abdominal pain as in our case. Tumors were treated by resection with or without adjuvant Imatinib.ConclusionSurgeons and oncologists should bear in mind this rare diagnosis and know how to treat it.



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Tumeurs malignes des gaines nerveuses périphériques intracérébrales métastatiques : à propos de deux cas et revue exhaustive des cas de la littérature

Publication date: Available online 27 February 2016
Source:Cancer/Radiothérapie
Author(s): C. Le Fèvre, J. Castelli, C. Perrin, P.L. Hénaux, G. Noël
Les tumeurs malignes des gaines nerveuses périphériques sont des tumeurs rares qui peuvent être associées à une neurofibromatose de type 1, ayant un pronostic défavorable, dont le traitement repose sur la chirurgie. La radiothérapie et la chimiothérapie sont des traitements de seconde ligne fréquemment utilisés mais dont l'efficacité reste à démontrer. Ces tumeurs, dont le diagnostic est clinique, radiologique histologique et immunohistochimique, ont un potentiel de récidive locale important. Des métastases à distance peuvent survenir mais sont rares. Les localisations tumorales observées sont variables et rarement intracérébrales. Nous rapportons deux cas de tumeurs malignes intracérébrales des gaines nerveuses périphériques métastatiques. Le premier cas était celui d'une femme de 68ans qui souffrait de céphalées et d'une diplopie, chez laquelle le diagnostic de tumeur maligne des gaines nerveuses périphériques frontotemporale gauche a été posé. Elle a été traitée initialement par chirurgie et irradiation. Dix mois après le diagnostic, il a été découvert une récidive locale et des métastases osseuses rachidiennes, traitées par vertébroplastie et irradiation. La patiente est décédée 15 mois après le diagnostic. Le deuxième cas était une celui d'une femme de 47ans qui souffrait de signes d'hypertension intracrânienne. Il avait été découvert une tumeur maligne des gaines nerveuses périphériques frontale droite traitée par chirurgie et irradiation. La patiente a été atteinte de trois récidives locales, traitées par chirurgie, et de localisations métastatiques concomitantes osseuses et pulmonaires, dont le traitement a été une chimiothérapie. Elle était vivante 20 mois après le diagnostic initial. Nous avons dénombré, dans une revue de la littérature, 25 cas de tumeurs malignes intracérébrales des gaines nerveuses périphériques, dont les deux cas présentés ci-dessus.Malignant peripheral nerve sheath tumours are extremely rare and can be associated with neurofibramatosis type 1. Their prognosis is poor and surgery remains the mainstay of therapy and should be the first line of treatment. Radiotherapy and chemotherapy are second line treatment and their effectiveness remains to demonstrate. The diagnosis is clinical, radiological, histological and immunohistochemical. Malignant peripheral nerve sheath tumours have a potential of local tumour recurrence very high and can metastasize. They often occur in extremity of the members but also rarely into brain. We report two cases of intracerebral nerve sheath tumour. The first was a 68-year-old woman who was admitted with progressive symptoms of headache and diplopia. A left frontotemporal malignant peripheral nerve sheath tumours was diagnosed and was treated by surgery and irradiation. Ten months later, she presented a local recurrence and spine bone's metastases were treated by vertebroplasty and irradiation. The patient died 15 months after the diagnosis. The second case was a 47-year-old woman who was referred because headache and vomiting symptoms. A right frontal malignant peripheral nerve sheath tumours was diagnosed and treated by surgery and irradiation. After that, the patient had three local recurrence operated and pulmonary and cranial bone's metastases. She was still alive after 20 months. We propose a literature review with 25 cases of intracerebral nerve sheath tumour identified, including the two current cases.



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Editorial Board

Publication date: March–April 2016
Source:Practical Radiation Oncology, Volume 6, Issue 2





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Table of Contents

Publication date: March–April 2016
Source:Practical Radiation Oncology, Volume 6, Issue 2





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Masthead

Publication date: March–April 2016
Source:Practical Radiation Oncology, Volume 6, Issue 2





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Selective Activator Protein-1 Inhibitor T-5224 Prevents Lymph Node Metastasis in an Oral Cancer Model

Summary

Activator protein-1 (AP-1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP-1 inhibitor–T-5224–in preventing lymph-node metastasis in head and neck squamous-cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T-5224 on HNSCC cell invasion, migration, proliferation, and matrix-metalloproteinase activity by performing an in vitro study using an invasion assay, scratch assay, WST-8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time-lapse microscopy. Furthermore, cervical lymph-node metastasis was assessed using an orthotopic tumor model of human oral squamous-cell carcinoma cells (HSC-3-M3) injected in the tongue of a BALB/c nude mouse. T-5224 (150 mg/kg) or vehicle was administered orally every day for 4 weeks. Animals were sacrificed and assessed for lymph-node metastasis by hematoxylin-eosin staining of resected lymph nodes. T-5224 significantly inhibited the invasion, migration, and matrix-metalloproteinase activity of HNSCC cells in a dose-dependent manner; there was no significant influence on cell proliferation. The anti-metastatic effect of T-5224 was also confirmed in our animal study. The rate of cervical lymph-node metastasis in the model was 40.0% in the T-5224-treated group (n = 30) versus 74.1% in the vehicle-treated group (n = 27; P < 0.05). In conclusion, T-5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph-node metastasis in head and neck cancer in an animal model.

This article is protected by copyright. All rights reserved.

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The Effect of Food on the Pharmacokinetics of TAS-102 and its Efficacy and Safety in Patients with Advanced Solid Tumors

Summary

TAS-102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS-102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single-dose, two-treatment (fed versus fasting), two-period, two-sequence crossover design, followed by repeated administration. Patients were administered single doses of TAS-102 (35 mg/m²) in the pharmacokinetic phase and received twice-daily doses of TAS-102 in 28-day cycles in the repeated administration phase for evaluating efficacy and safety. Food showed no effect on the area under the curve from 0–12 h or 0 h–infinity values of trifluridine following administration of TAS-102 under fasting and fed conditions, whereas those of tipiracil hydrochloride decreased by approximately 40%. Maximum concentrations of both drugs decreased by approximately 40%, indicating that food influenced the absorption and bioavailability of trifluridine and tipiracil hydrochloride, respectively. During the repeated administration, stable disease was observed in nine patients with rectal, small-cell lung, breast, thymic, duodenal, and prostate cancers. Major adverse events were neutropenia, leukopenia, anemia, and nausea. Postprandial administration was optimal for TAS-102 because trifluridine's area under the curve was not changed by food, indicating that its clinical efficacy would not be affected. Additionally, postprandial administration was reasonable because the maximum concentration of trifluridine decreased in neutrophils, which correlated with previous studies. These results suggest that TAS-102 would be an effective treatment for small-cell lung, thymic, and colorectal cancers

This article is protected by copyright. All rights reserved.

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The role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains the most deadly disease worldwide, with the lowest survival rate among all cancer types. Recent evidence suggests hyaluronan (HA), a major component of extracellular matrix, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized typically by a dense desmoplastic stroma containing a large amount of HA. Accumulation of HA promotes tumor growth in mice and correlates with poor prognosis in patients with PDAC. Because HA is involved in various malignant behaviors of cancer (such as increased cell proliferation, migration, invasion, angiogenesis, and chemoresistance), inhibiting HA synthesis/signaling or depleting HA in tumor stroma could represent a promising therapeutic strategy against PDAC. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.

This article is protected by copyright. All rights reserved.

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Dietary acrylamide and the risk of endometrial cancer: An Italian case-control study.

Related Articles

Dietary acrylamide and the risk of endometrial cancer: An Italian case-control study.

Nutr Cancer. 2016 Feb 23;:1-6

Authors: Pelucchi C, Galeone C, Negri E, Bosetti C, Serraino D, Montella M, Talamini R, La Vecchia C

Abstract
The role of dietary acrylamide on the risk of hormone-related, and specifically endometrial, cancers is debated. Epidemiological data are scanty. Thus, we examined the relation between acrylamide intake and endometrial cancer risk in a case-control study conducted between 1992 and 2006 in 3 Italian areas. Cases were 454 women with incident, histologically confirmed endometrial cancer. Controls were 908 age-matched women admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. The OR of endometrial cancer for increasing quintiles of dietary acrylamide, as compared to the lowest one, were 1.02 (95% CI: 0.67-1.54), 1.20 (95% CI: 0.80-1.80), 1.00 (95% CI: 0.65-1.54) and 1.17 (95% CI: 0.73-1.85). The OR for an increase of 10 μg/day of dietary acrylamide was 1.00 (95% CI: 0.91-1.10). In subgroup analyses, the ORs for high vs. low acrylamide intake were 1.28 (95% CI: 0.73-2.25) in never smokers and 1.14 (95% CI: 0.45-2.90) in ever smokers. Our data do not support an association between dietary acrylamide intake and endometrial cancer.

PMID: 26905095 [PubMed - as supplied by publisher]

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Vitamin D receptor polymorphisms relate to risk of adenomatous polyps in a sex-specific manner.

Related Articles

Vitamin D receptor polymorphisms relate to risk of adenomatous polyps in a sex-specific manner.

Nutr Cancer. 2016 Feb 23;:1-8

Authors: Beckett EL, Gras KL, Martin C, Boyd L, Ng X, Duesing K, Yates Z, Veysey M, Lucock M

Abstract
Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP.

PMID: 26904920 [PubMed - as supplied by publisher]

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Issue Information

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Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs

Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.

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In This Issue

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Co-localization of Ki67, CD44v adn deltaNp63 in the invasive front of lung squamous cell carcinoma

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Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer.

Related Articles

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer.

Cancer Biol Ther. 2016 Jan 30;:1-8

Authors: Li Y, Li Y, Liu J, Fan Y, Li X, Dong M, Liu H, Chen J

Abstract
Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.

PMID: 26909466 [PubMed - as supplied by publisher]

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Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer.

Related Articles

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer.

Cancer Biol Ther. 2016 Jan 30;:1-8

Authors: Li Y, Li Y, Liu J, Fan Y, Li X, Dong M, Liu H, Chen J

Abstract
Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.

PMID: 26909466 [PubMed - as supplied by publisher]

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Cancers, Vol. 8, Pages 27: Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing.

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Cancers, Vol. 8, Pages 29: Eugenia jambolana (Java Plum) Fruit Extract Exhibits Anti-Cancer Activity against Early Stage Human HCT-116 Colon Cancer Cells and Colon Cancer Stem Cells

The World Health Organization predicts over a 70% increase in cancer incidents in developing nations over the next decade. Although these nations have limited access to novel therapeutics, they do have access to foods that contain chemopreventive bioactive compounds such as anthocyanins, and as such, consumption of these foods can be encouraged to combat cancer. We and others have previously characterized the anti-colon cancer properties of dietary anthocyanins from different sources. Eugenia jambolana (Java plum) is a tropical medicinal fruit rich in anthocyanins, however, its anti-colon cancer properties are not well characterized. Furthermore, recent evidence suggests that colon cancer stem cells (colon CSCs) promote resistance to chemotherapy, relapse of tumors and contribute to poor prognosis. The objectives of this study were to 1) characterize the anthocyanin profile of Java plum using HPLC-MS; and 2) determine the anti-proliferative (cell counting and MTT) and pro-apoptotic (TUNEL and caspase 3/7 glo assay) properties of Java plum fruit extract (JPE) using HCT-116 colon cancer cell line and colon CSCs (positive for CD 44, CD 133 and ALDH1b1 markers). HPLC-MS analysis showed that JPE contains a variety of anthocyanins including glucosides of delphinidin, cyanidin, petunidin, peonidin and malvidin. JPE anthocyanins suppressed (p < 0.05) proliferation in HCT-116 cells and elevated (p < 0.05) apoptosis in both HCT-116 cells and colon CSCs. JPE also suppressed the stemness in colon CSCs as evaluated using colony formation assay. These results warrant further assessment of the anti-cancer activity of JPE, and its molecular mechanisms using pre-clinical models of colon cancer.

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A longitudinal exploration of the psychological resources influencing depression and anxiety in newly diagnosed Asian persons with cancer

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Psychological variables associated with quality of life following primary treatment for head and neck cancer: a systematic review of the literature from 2004 to 2015

Abstract

Objective

There has been a recent proliferation of research on quality of life (QoL) in head and neck cancer (HNC). The objective of this review was to systematically examine the evidence on psychological factors associated with QoL outcomes for HNC survivors in the post-treatment period published during 2004–2015.

Methods

Five databases were searched for studies investigating psychological factors associated with QoL in HNC survivors. Empirical studies published between January 2004 and June 2015 were included if they measured QoL as an outcome following treatment using a reliable and valid measure, examined its association with at least one psychological factor and included at least 50 HNC survivors.

Results

Twenty-four publications describing 19 studies (9 cross-sectional, 10 prospective) involving 2,263 HNC survivors were included. There was considerable heterogeneity in study design and diversity in measurement and analysis. Distress-related variables (depression, anxiety, distress) were most frequently investigated, and mostly reported negative associations with QoL outcomes. Associations were also observed between other psychological factors (e.g., coping, neuroticism and fear of recurrence) and QoL.

Conclusions

Several psychological factors predict QoL among HNC survivors who have completed treatment. Routine screening and early interventions that target distress could improve HNC survivors' QoL following treatment. Longitudinal and population-based studies incorporating more systematic and standardised measurement approaches are needed to better understand relationships between psychological factors and QoL and to inform the development of intervention and supportive care strategies. Copyright © 2016 John Wiley & Sons, Ltd.

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Survival after resection of perihilar cholangiocarcinoma--development and external validation of a prognostic nomogram

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Autologous flap breast reconstruction: Surgical algorithm and patient selection

Whole breast reconstruction using autologous tissue is the gold standard in many regions of the world. Reasons include breast replacement with native skin and fat, ability to shape and mold the tissue into a breast, no foreign materials are necessary, and it lasts forever when successful. There are now many options for autologous breast reconstruction and the decision making process regarding which flap to choose will depend on ones experience and comfort, ability to perform microvascular surgery, and the milieu in which one operates. This chapter will review many of the options for autologous breast reconstruction and provide an algorithmic approach for flap and patient selection. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Implant-based breast reconstruction: Strategies to achieve optimal outcomes and minimize complications

Breast reconstruction using prosthetic devices is the most commonly performed procedure in women following mastectomy. The goal is to provide an outcome that is predictable and reproducible while minimizing complications and optimizing aesthetics. There are various strategies by which this can be achieved. It begins with proper patient selection because most adverse events occur in high-risk patients. This in turn is related to the timing of the reconstruction that can be performed immediately following the mastectomy or on a delayed basis. Many surgeons have been combining the use of acellular dermal matrices with prosthetic devices that require strict attention to detail to ensure success. There are various options for achieving device coverage that include total muscle, partial muscle, and subcutaneous coverage. The radiated patient poses additional challenges and limitations that must be understood to achieve a desired outcome. Finally, autologous fat grafting has become a valuable tool to improve outcomes in both radiated and non-radiated women. These factors will be reviewed with the intent of improving outcomes and minimizing complications in the setting of prosthetic breast reconstruction. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Rapamycin Dosage

The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes both mTOR complexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics. Mol Cancer Ther; 15(3); 1–7. ©2016 AACR.

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A Novel RAF Inhibitor with DFG-Out-Binding Mode

BI 882370 is a highly potent and selective RAF inhibitor that binds to the DFG-out (inactive) conformation of the BRAF kinase. The compound inhibited proliferation of human BRAF–mutant melanoma cells with 100x higher potency (1–10 nmol/L) than vemurafenib, whereas wild-type cells were not affected at 1,000 nmol/L. BI 882370 administered orally was efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, and at 25 mg/kg twice daily showed superior efficacy compared with vemurafenib, dabrafenib, or trametinib (dosed to provide exposures reached in patients). To model drug resistance, A375 melanoma–bearing mice were initially treated with vemurafenib; all tumors responded with regression, but the majority subsequently resumed growth. Trametinib did not show any efficacy in this progressing population. BI 882370 induced tumor regression; however, resistance developed within 3 weeks. BI 882370 in combination with trametinib resulted in more pronounced regressions, and resistance was not observed during 5 weeks of second-line therapy. Importantly, mice treated with BI 882370 did not show any body weight loss or clinical signs of intolerability, and no pathologic changes were observed in several major organs investigated, including skin. Furthermore, a pilot study in rats (up to 60 mg/kg daily for 2 weeks) indicated lack of toxicity in terms of clinical chemistry, hematology, pathology, and toxicogenomics. Our results indicate the feasibility of developing novel compounds that provide an improved therapeutic window compared with first-generation BRAF inhibitors, resulting in more pronounced and long-lasting pathway suppression and thus improved efficacy. Mol Cancer Ther; 15(3); 1–12. ©2016 AACR.

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A brighter future? The impact of insurance and socioeconomic status on cancer outcomes in the USA: a review

Future Oncology Ahead of Print.


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A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study

In this phase III study, metastatic breast cancer patients who had had a response on first-line taxane and bevacizumab treatment were randomized to continue on this regimen or to receive endocrine therapy plus bevacizumab. We failed to show superior efficacy of the endocrine treatment maintenance strategy compared with the continuation of the treatment that have achieved initial tumor control.

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Tumor MGMT promoter hypermethylation changes over time limit temozolomide efficacy in a phase II trial for metastatic colorectal cancer

This study indicates that temozolomide has limited activity in mCRC selected by MGMT hypermethylation, and show for the first time that tumor MGMT methylation can change from diagnosis, decaying after several lines of treatments. This result points out the need to test baseline tumor biopsy or plasma in order to refine target selection in trials with alkylating agents performed in this setting.

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Posttraumatic growth among head and neck cancer survivors with psychological distress

Abstract

Background

Information on posttraumatic growth (PTG) among head and neck cancer (HNC) survivors with a high level of distress is limited. The aim of this cross-sectional study was to investigate the occurrence of PTG among distressed HNC survivors and its association with anxiety, depressive, nicotine, and alcohol use disorders and health-related quality of life.

Methods

Seventy-four HNC survivors with psychological distress (Hospital Anxiety and Depression Scale (HADS) anxiety > 7 and/or HADS depression > 7) completed the Posttraumatic Growth Inventory, which comprises five subscales: relating to others, new possibilities, personal strength, spiritual change, and appreciation of life, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Anxiety, depressive, nicotine, and alcohol use disorders were measured using the Composite International Diagnostic Interview.

Results

Moderate to high Posttraumatic Growth Inventory (PTGI) scores occurred in 10% of the HNC survivors with distress. The mean total PTGI score was 30.8 (SD = 19.7), with the highest mean score on the subscale relating to others. A multivariate regression model consisting of tumor stage, anxiety disorder, alcohol use disorder, and social functioning predicted total PTGI score best (F(4, 64) = 7.565, p < .000, R² = .321).

Conclusions

The presence of PTG in this population of distressed HNC survivors was low. PTG occurred most in the domain of relating to others. Among distressed HNC survivors, higher PTG was associated with lower tumor stage, absence of an anxiety disorder, absence of an alcohol use disorder, and better social functioning. Copyright © 2016 John Wiley & Sons, Ltd.

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Statins and the risk of pancreatic cancer in Type 2 diabetic patients: Immortal time bias in survival analysis?

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Hypertensive disorders of pregnancy and subsequent risk of solid cancer – a nationwide cohort study

ABSTRACT

Women with hypertensive disorders of pregnancy (HDP) have higher levels of anti-angiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and non-melanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had ≥1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval [CI] 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency towards reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers, and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP anti-angiogenic state or an innate tendency toward anti-angiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding. This article is protected by copyright. All rights reserved.

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Neo-adjuvant therapy or definitive chemoradiotherapy can improve laryngeal preservation rates in patients with cervical esophageal cancer. A Japanese nationwide survey

Abstract

Background

Various options are available to treat cervical esophageal cancer (CEC), including primary resection, neo-adjuvant therapy followed by surgery, and definitive chemoradiotherapy (dCRT). However, whether neo-adjuvant therapy or dCRT can improve larynx preservation rates in patients with CEC is unclear. This study investigated results of CEC treatment in clinical practice by a nationwide survey in Japan.

Patients and methods

We retrospectively investigated results of clinical practices for patients with resectable CEC treated between 2012 and 2014, using a mailed questionnaire as a nationwide survey to 308 institutions recognized by the Japan Esophageal Society and the Japan Broncho-Esophagological Society.

Results

We registered 792 patients from 93 institutions, of whom 11.1 % underwent endoscopic resection, 46.0 % underwent surgery, and 39.2 % underwent dCRT. Among patients with CEC who were considered to be poor candidates for laryngeal preservation at initial diagnosis, 24.5 % of the 139 patients treated with neo-adjuvant therapy, and 47.3 % of the 226 patients treated with dCRT preserved their larynxes.

Conclusions

This questionnaire survey revealed that multimodality treatment for CEC could decrease laryngectomy rates, especially among patients who were not considered to be laryngeal preservation candidates. These treatment strategies can lead to both laryngeal preservation and postoperative quality of life, and should become more widely used.

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Clinical efficacy of liver resection after downsizing systemic chemotherapy for initially unresectable liver metastases

Abstract

Background

This study sought to clarify the clinical benefits of liver resection after downsizing systemic chemotherapy for initially unresectable colorectal liver metastases (CLM).

Methods

Survival and clinical characteristics of CLM patients who underwent resection between January 2001 and December 2013 were retrospectively assessed. The study cohort of 88 patients with limited liver disease who underwent curative liver resection comprised 34 with initially resectable synchronous disease (synchronous group), 38 with initially resectable metachronous disease (metachronous group), and 16 with initially unresectable converted disease (conversion group).

Results

The median duration of follow-up for the overall study population was 33 (1–98) months. Overall survival (OS) in the conversion group was not significantly different from that in the other groups. However, disease-free survival (DFS) in the conversion group was significantly shorter than that in the synchronous group. The median DFS was 19.1 months in the synchronous group, 16.6 months in the metachronous group, and 15.3 months in the conversion group. Most patients in the conversion group had recurrence shortly after liver resection in the remnant liver with or without metastases at other sites, but many could undergo repeat hepatectomy or resection of the metastases at other sites.

Conclusions

Although the converted patients tended to have recurrence shortly after liver resection, survival could be prolonged by repeat hepatectomy or resection of metastases at other sites. Liver resection after downsizing chemotherapy appears to be efficacious for patients with initially unresectable CLM and may result in long-term outcomes equivalent to those of patients with initially resectable CLM.

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Hermes

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Development of bilateral coronary artery aneurysms in a child with Noonan syndrome

Abstract

Noonan syndrome is a constellation of congenital malformations including heart defects, facial anomalies and short stature. The cardiovascular defects are variable and extensive, with the most common being pulmonary stenosis and hypertrophic cardiomyopathy. Coronary artery anomalies have only been reported in a few cases. We report a child with Noonan syndrome status post pulmonary stenosis and atrial septal defect repair, who developed bilateral coronary artery aneurysms. The aneurysms were diagnosed with both cardiac magnetic resonance imaging and coronary computed tomography angiography. There had been no evidence of them on a cardiac MR exam 5 years previously.

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Pediatric Radiology Continuing Medical Education Activity

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Depletion of histone demethylase KDM5B inhibits cell proliferation of hepatocellular carcinoma by regulation of cell cycle checkpoint proteins p15 and p27

KDM5B is a jmjc domain-containing histone demethylase which remove tri-, di-, and monomethyl groups from histone H3 lysine 4 (H3K4). KDM5B has been determined as an oncogene in many malignancies. However, its ...

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Distribution and features of hematological malignancies in Eastern Morocco: a retrospective multicenter study over 5 years

Abstract

Background

Hematological malignancies (HM) are a public health problem. The pattern and distribution of diagnosed hematological cancers vary depending on age, sex, geography, and ethnicity suggesting the involvement of genetic and environmental factors for the development of these diseases. To our knowledge, there is no published report on HM in the case of Eastern Morocco. In this report we present for the first time the overall pattern of HM for this region.

Methods

Retrospective descriptive study of patients diagnosed with HM between January 2008 and December 2012 in three centres in Eastern Morocco providing cancer diagnosis, treatment or palliative care services. The FAB (French-American-British) classification system has been taken into account in the analysis of myeloid and lymphoid neoplasms.

Results

In this study, a total of 660 cases of HM were registered between January 2008 and December 2012. Overall, 6075 cases of cancers all sites combined were registered during this study period, indicating that HM account for around 10.9 % (660/6075) of all cancers recorded. Among the 660 registered cases of HM, 53 % were males and 47 % were females, with a male to female ratio of 1.1. Thus, overall, men are slightly more affected with HM than women. By contrast, a female predominance was observed in the case of Hodgkin's lymphoma (HL), myeloproliferative neoplasms (MPN), acute myeloid leukemia (AML) and the myelodysplastic syndrome (MDS). HM occur at a relatively young age, with an overall median age at diagnosis of 54 years. Non-Hodgkin's lymphoma (NHL) was the most common HM accounting for 29.7 % of all HM, followed by HL, MPN, multiple myelomas (MM), chronic lymphocytic leukemia (CLL), AML, MDS, acute lymphoblastic leukemia (ALL), and Waldenström macroglobulinemia (WM). The majority of HM cases have been observed among patients aged 60 years and over (40.4 % of HM). Among this age group, NHL was the most common HM. In adolescents, HL was the most frequent HM.

Conclusions

This study provided for the first time the pattern and distribution of HM in Eastern Morocco. Our findings justify the need to establish a regional cancer registry as a first step in blood cancer control in Eastern Morocco.

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Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448

Abstract

Background

Triple negative breast cancers (TNBC) possess cell dedifferentiation characteristics, carry out activities connate to those of cancer stem cells (CSCs) and are associated with increased metastasis, as well as, poor clinical prognosis. The regulatory mechanism of this highly malignant phenotype is still poorly characterized. Accruing evidence support the role of non-coding RNAs (ncRNAs) as potent regulators of CSC and metastatic gene expression, with their dysregulation implicated in tumorigenesis and disease progression.

Methods

In this study, we investigated TNBC metastasis, metastasis-associated genes and potential inhibitory mechanisms using bioinformatics, tissue microarray analyses, immunoblotting, polymerase chain reaction, loss and gain of gene function assays and comparative analyses of data obtained.

Results

Compared with other breast cancer types, the highly metastatic MDA-MB-231 cells concurrently exhibited increased expression levels of Lysine-specific demethylase 5B protein (KDM5B) and long non-coding RNA (lncRNA), MALAT1, suggesting their functional association. KDM5B-silencing in the TNBC cells correlated with the upregulation of hsa-miR-448 and led to suppression of MALAT1 expression with decreased migration, invasion and clonogenic capacity in vitro, as well as, poor survival in vivo. This projects MALAT1 as a mediator of KDM5B oncogenic potential and highlights the critical role of this microRNA, lncRNA and histone demethylase in cancer cell motility and metastatic colonization. Increased expression of KDM5B correlating with disease progression and poor clinical outcome in breast cancer was reversed by hsa-miR-448.

Conclusions

Our findings demonstrate the critical role of KDM5B and its negative regulator hsa-miR-448 in TNBC metastasis and progression. Hsa-miR-448 disrupting KDM5B-MALAT1 signalling axis and associated activities in TNBC cells, projects it as a putative therapeutic factor for selective eradication of TNBC cells.

Graphical abstract

KDM5B, MALAT1 and hsa-miR-448 are active looped components of the epigenetic poculo mortis in aggressive breast cancer.

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The anti-oxidative transcription factor Nuclear factor E2 related factor-2 (Nrf2) counteracts TGF-β1 mediated growth inhibition of pancreatic ductal epithelial cells -Nrf2 as determinant of pro-tumorigenic functions of TGF-β1

Abstract

Background

Nuclear factor E2 related factor-2 (Nrf2) is an oxidative stress inducible transcription factor being essential in regulating cell homeostasis. Thus, acute induction of Nrf2 in epithelial cells exposed to inflammation confers protection from oxidative cell damage and mutagenesis supporting an anti-tumorigenic role for Nrf2. However, pancreatic ductal adenocarcinoma (PDAC) is characterized by persistent Nrf2 activity conferring therapy resistance which points to a pro-tumorigenic role of Nrf2. A similar dichotomous role in tumorigenesis is described for the Transforming Growth Factor-beta 1 (TGF-β1). The present study therefore aimed at elucidating whether the switch of Nrf2 function towards a tumor promoting one relates to the modulation of TGF-β1 induced cell responses and whether this might occur early in PDAC development.

Methods

In situ analysis comprised immunohistochemical stainings of activated (phosphorylated) Nrf2 and Ki67 in pancreatic tissues containing normal ducts and pancreatic intraepithelial neoplasia (PanINs). In vitro, Nrf2 levels in benign (H6c7-pBp), premalignant (H6c7-kras) and malignant (Colo357) pancreatic ductal epithelial cells were modulated by Nrf2 specific siRNA or Nrf2 overexpression. Then, the effect of Nrf2 alone and in combination with TGF-β1 on cell growth and survival was investigated by cell counting, Ki67 staining and apoptosis assays. The underlying cell signaling was investigated by western blotting. Statistical analysis was performed by Shapiro-Wilk test for normal distribution. Parametric data were analyzed by one-way ANOVA, while non-parametric data were analyzed by Kruskal-Wallis one-way ANOVA on ranks.

Results

Significantly elevated expression of activated Nrf2 and Ki67 could be detected in PanINs but not in normal pancreatic ductal epithelium. While the effect of Nrf2 on basal cell growth of H6c7-pBp, H6c7-kras and Colo357 cells was minor, it clearly attenuated the growth inhibiting effects of TGF-β1 in all cell lines. This enhanced Nrf2-mediated cell survival was predominantly based on an enhanced proliferative activity. Accordingly, expression of p21 expression along with expression of phospho-p38 and phospho-Smad3 was diminished whereas Erk-phosphorylation was enhanced under these conditions.

Conclusions

Overall, our data demonstrate that Nrf2 being elevated in early precursor lesions counteracts the growth inhibiting function of TGF-β1 already in benign and premalignant pancreatic ductal epithelial cells. This could represent one fundamental mechanism underlying the functional switch of both- TGF-β1 and Nrf2 – which may manifest already in early stages of PDAC development.

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Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma

Abstract

Background

Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.

Methods

We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.

Results

A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4–67.4) and the disease control rate was 85.7 % (60.0–96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6–12.2 months), and median overall survival was 30.0 months (range, 6.2–41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.

Conclusions

S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.

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Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography

Abstract

Background

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study.

Methods

From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted.

Results

In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28–74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19–9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116).

Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000).

Conclusions

The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.

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Change in weight and waist circumference and risk of colorectal cancer: results from the Melbourne Collaborative Cohort Study

Abstract

Background

Studies reporting the association between change in weight or body mass index during midlife and risk of colorectal cancer have found inconsistent results, and only one study to date has reported the association between change in waist circumference (a measure of central adiposity) and risk of colorectal cancer.

Methods

We investigated the association between risk of colorectal cancer and changes in directly measured waist circumference and weight from baseline (1990-1994) to wave 2 (2003-2007). Cox regression, with age as the time metric and follow-up starting at wave 2, adjusted for covariates selected from a causal model, was used to estimate the Hazard Ratios (HRs) and 95 % Confidence Intervals (CIs) for the change in waist circumference and weight in relation to risk of colorectal cancer.

Results

A total of 373 cases of colorectal cancer were diagnosed during an average 9 years of follow-up of 20,605 participants. Increases in waist circumference and weight were not associated with the risk of colorectal cancer (HR per 5 cm increase in waist circumference = 1.02; 95 % CI: 0.95, 1.10; HR per 5 kg increase in weight = 0.93; 0.85, 1.02). For individuals with a waist circumference at baseline that was less than the sex-specific mean value there was a slight increased risk of colorectal cancer associated with a 5 cm increase in waist circumference at wave 2 (HR = 1.08; 0.97, 1.21).

Conclusion

Increases in waist circumference and weight during midlife do not appear to be associated with the risk of colorectal cancer.

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Erratum to: Human papillomavirus types in non-cervical high-grade intraepithelial neoplasias and invasive carcinomas from San Luis Potosí, Mexico: a retrospective cross-sectional study

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Activity-based cost analysis of hepatic tumor ablation using CT-guided high-dose rate brachytherapy or CT-guided radiofrequency ablation in hepatocellular carcinoma

To analyse and compare the costs of hepatic tumor ablation with computed tomography (CT)-guided high-dose rate brachytherapy (CT-HDRBT) and CT-guided radiofrequency ablation (CT-RFA) as two alternative minimal...

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Case 6-2016: A 10-Year-Old Boy with Abdominal Cramping and Fevers

Presentation of Case. Dr. Hasan Merali (Pediatrics): A 10-year-old boy was seen in the gastroenterology clinic of this hospital because of intermittent abdominal cramping and fevers. The patient had been well until approximately 3 weeks before this presentation, when intermittent fevers to a…

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Genotyping of Colorectal Cancer for Cancer Precision Medicine: Results from the IPH Center for Molecular Pathology

ABSTRACT

Cancer precision medicine has opened up new avenues for the treatment of colorectal cancer (CRC). To fully realize its potential, high-throughput sequencing platforms that allow genotyping beyond KRAS need to be implemented and require performance assessment. We comprehensively analyzed first-year data of 202 consecutive formalin-fixed paraffin embedded (FFPE) CRC samples for which prospective genotyping at our institution was requested. Deep targeted genotyping was done using a semiconductor-based sequencing platform and a self-designed panel of 30 CRC-related genes. Additionally, microsatellite status (MS) was determined. Ninety-seven percent of tumor samples were suitable for sequencing and in 88% MS could be assessed. The minimal drop-out rates of 6 and 25 cases respectively were due to too low amounts or heavy degradation of DNA. Of 557 non-synonymous mutations, 90 (16%) have not been described in COSMIC at the time of data query. Forty-three cases (22%) had double- or triple mutations affecting a single gene. Sixty-four percent had genetic alterations influencing oncological therapy. Eight percent of patients (MSI phenotype: 6%; mutated POLE: 2%) were potentially eligible for treatment with immune checkpoint inhibitors. Of 56% of KRASwt CRC that potentially qualified for anti-EGFR treatment, 30% presented with mutations in BRAF/NRAS. Mutated PIK3CA was detected in 21%. In conclusion, we here present real-life routine diagnostics data that not only demonstrate the robustness and feasibility of deep targeted sequencing and MS-analysis of FFPE CRC samples but also contribute to the understanding of CRC genetics. Most importantly, in more than half of the patients our approach enabled the selection of the best treatment currently available. This article is protected by copyright. All rights reserved.

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Establishment of proliferative tetraploid cells from telomerase-immortalized normal human fibroblasts

Abstract

Aneuploidy is observed in the majority of human cancers and is considered to be causally related to carcinogenesis. Although malignant aneuploid cells are suggested to develop from polyploid cells formed in precancerous lesions, the mechanisms of this process remain elusive. This is partly because no experimental model is available where nontransformed polyploid human cells propagate in vitro. We previously showed that proliferative tetraploid cells can be established from normal human fibroblasts by treatment with the spindle poison demecolcine (DC). However, the limited lifespan of these cells hampered detailed analysis of a link between chromosomal instability and the oncogenic transformation of polyploid cells. Here, we report the establishment of proliferative tetraploid cells from the telomerase-immortalized normal human fibroblast cell line TIG-1. Treatment of immortalized diploid cells with DC for 4 days resulted in proliferation of cells with tetraploid DNA content and near-tetraploid/tetraploid chromosome counts. Established tetraploid cells had functional TP53 despite growing at almost the same rate as diploid cells. The frequency of clonal and sporadic chromosome aberrations in tetraploid cells was higher than in diploid cells and in one experiment, gradually increased with repeated subculture. This study suggests that tetraploid cells established from telomerase-immortalized normal human fibroblasts can be a valuable model for studying chromosomal instability and the oncogenic potential of polyploid cells. This article is protected by copyright. All rights reserved.

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Most US Cancer Prevention Guidelines Dont Provide Information Needed for Decision-Making

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Presenting Benefits and Downsides to Facilitate High-Quality Decision-Making About Cancer Screening

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Presentation of Benefits and Harms in US Cancer Screening and Prevention Guidelines: Systematic Review

Background:

Cancer prevention and screening guidelines are ideally suited to the task of providing high-quality benefit-harm information that informs clinical practice. We systematically examined how US guidelines present benefits and harms for recommended cancer prevention and screening interventions.

Methods:

We included cancer screening and prevention recommendations from: 1) the United States Preventive Services Task Force, 2) the American Cancer Society, 3) the American College of Physicians, 4) the National Comprehensive Cancer Network, and 5) other US guidelines within the National Guidelines Clearinghouse. Searches took place November 20, 2013, and January 1, 2014, and updates were reviewed through July 1, 2015. Two coders used an abstraction form to code information about benefits and harms presented anywhere within a guideline document, including appendices. The primary outcome was each recommendation's benefit-harm "comparability" rating, based on how benefits and harms were presented. Recommendations presenting absolute effects for both benefits and harms received a "comparable" rating. Other recommendations received an incomplete rating or an asymmetric rating based on prespecified criteria.

Results:

Fifty-five recommendations for using interventions to prevent or detect breast, prostate, colon, cervical, and lung cancer were identified among 32 guidelines. Thirty point nine percent (n = 17) received a comparable rating, 14.5% (n = 8) received an incomplete rating, and 54.5% (n = 30) received an asymmetric rating.

Conclusions:

Sixty-nine percent of cancer prevention and screening recommendation statements either did not quantify benefits and harms or presented them in an asymmetric manner. Improved presentation of benefits and harms in guidelines would better ensure that clinicians and patients have access to the information required for making informed decisions.

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A Rare Case of Multilocular Thymic Cyst with Follicular Lymphoid Hyperplasia: Radiologic and Histopathologic Features

Abstract

Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

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Indeterminate Findings on Oncologic PET/CT: What Difference Does PET/MRI Make?

Abstract

Background

Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies.

Methods

A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16 %) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies.

Results

In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases, the definitive PET/MRI interpretation proved correct. These 12 patients underwent six additional diagnostic studies to clarify the initial indeterminate PET/CT findings. In the remaining 13 of 31 cases with indeterminate findings on both PET/CT and PET/MRI, common reasons for uncertainty included the inability to distinguish reactive from malignant lymphadenopathy (4/13) and local recurrence from treatment effect (2/13).

Conclusions

Indeterminate PET/CT findings can result in equivocal reads and additional diagnostic studies. PET/MRI may reduce the rate of indeterminate findings by facilitating better tumor staging, FDG activity localization, and lesion characterization. In our study, PET/MRI resulted in more definitive imaging interpretations with high accuracy. PET/MRI also showed potential in reducing the number of additional diagnostic studies prompted by PET/CT findings. Our results suggest that whole-body PET/MRI provides certain diagnostic advantages over PET/CT, promotes more definitive imaging interpretations, and may improve the overall clinical utility of PET.

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Instrumentation for Time-of-Flight Positron Emission Tomography

Abstract

Positron emission tomography (PET) is a molecular imaging modality that provides information at the molecular level. This system is composed of radiation detectors to detect incoming coincident annihilation gamma photons emitted from the radiopharmaceutical injected into a patient's body and uses these data to reconstruct images. A major trend in PET instrumentation is the development of time-of-flight positron emission tomography (ToF-PET). In ToF-PET, the time information (the instant the radiation is detected) is incorporated for image reconstruction. Therefore, precise and accurate timing recording is crucial in ToF-PET. ToF-PET leads to better localization of the annihilation event and thus results in overall improvement in the signal-to-noise ratio (SNR) of the reconstructed image. Several factors affect the timing performance of ToF-PET. In this article, the background, early research and recent advances in ToF-PET instrumentation are presented. Emphasis is placed on the various types of scintillators, photodetectors and electronic circuitry for use in ToF-PET, and their impact on timing resolution is discussed.

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Tumor volume is a better predictor of post-operative wound complications compared to tumor size in soft tissue sarcomas of the proximal lower extremity

Abstract

Background

Wide local excision with or without radiation therapy (RT) and chemotherapy is widely accepted as appropriate management for soft tissue sarcomas (STS) of the extremity. Although survival and local control rates are comparable to amputation, post-operative wound complications (WC) following limb salvage can result in significant morbidity for the patient. Certain risk factors such as location, pre-operative RT, and age have been shown to increase the risk of WCs. Somewhat surprisingly, size has not consistently been shown to impact WC rates. The goal of this study is to assess whether tumor volume, as opposed to the traditional measurement of the largest dimension in one plane, correlates with the development of post-operative WCs.

Methods

Between 2000 and 2013, 81 patients with STS of the proximal lower extremity, buttock and pelvis were retrospectively identified from our prospective database. We reviewed the impact of patient, tumor, and treatment variables on postoperative WC. Predictors for WC were evaluated using the Fisher exact test for univariate analysis and logistic regression for multivariate analysis. Tumor volume was determined using the medical image merge (MIM) ^® software program (version 6.5.4, MIM Software, Cleveland, OH). Tumor size (diameter) was determined the historical way of measuring the widest dimension on the sagittal, coronal, and axial planes from the MRI scan at midplane.

Results

The overall WC rate within 6 months of tumor resection was 32 %. WC were more likely to occur with larger tumor volumes (p = 0.015), although not with tumor diameters ≥10 cm (p = 0.55). Neither volume of subcutaneous fat (p = 0.34) or depth of the subcutaneous fat layer (p = 0.82) significantly impacted WC rates. Tumor proximity to skin surface also did not significantly impact WC risk (p = 0.73).

Conclusions

Increase in tumor volume led to a higher risk of post-operative WCs. Assessing tumor volume may allow clinicians to better counsel patients on their risk of post-operative WCs. Tumor volume, as opposed to size alone, should be considered in future sarcoma outcome studies.

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Gene Fusion May Drive Rare Childhood Brain Tumor

Researchers have identified a genetic rearrangement that may drive the development of a rare benign brain tumor in children. The rearrangement, which causes parts of two genes to fuse, may spur the growth of tumors through three distinct biological mechanisms simultaneously, the researchers found.

The study focused on angiocentric gliomas, a rare subtype of low-grade pediatric tumors that was first described less than a decade ago. Fewer than 30 cases have been reported in the scientific literature. Based on their findings, the study authors propose that angiocentric gliomas should be classified as a distinct biologic entity and that the presence of the gene fusion should be used to confirm the diagnosis.

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A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma

This phase I study evaluated combined panobinostat and epirubicin in patients with advanced solid tumors, establishing a MTD, and demonstrating a correlation between neutropenia, PBMC histone acetylation and clinical benefit. In a sarcoma expansion cohort, more than half of patients, having previously failed anthracycline therapy, benefited, suggesting HDAC inhibition reverses resistance.

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On the tumor risk from dental diagnostic X-ray exposure

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Comparison of prognostic and predictive impact of genomic or central grade and immunohistochemical subtypes or IHC4 in HR+/HER2- early breast cancer: WSG-AGO EC-Doc Trial

Central grade and luminal-A-like subtype were significant predictors of outcome if genomic grade as dichotomous factor (GG1/EQ vs. GG3) was included into the multivariate analysis in breast cancer patients treated by EC-Doc or FEC within the EC-Doc trial. Only continuous GGI but not IHC4 was strong prognostic factor beyond all other factorsin HR+/HER2- breast cancer even if central grade was available.

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Breast Cancer Incidence and Mortality: Trends over Forty Years among Women in Shanghai, China

With 40-years of cancer data from the oldest population-based cancer registry in China, this study evaluate secular time trends in breast cancer incidence and mortality in an urban Chinese population. Our results show a tremendous increase in incidence and a slight increase in mortality with significant age, cohort and period effects for breast cancer among women in urban Shanghai.

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Large-Scale Prospective Pharmacogenomics Study of Oxaliplatin-Induced Neuropathy in Colon Cancer Patients enrolled in the JFMC41-1001-C2 (JOIN Trial)

Our large-scale and prospective pharmacogenomics study of Japanese patients receiving protocol treatment of adjuvant mFOLFOX6 could not verify a role for any of the 12 SNP markers reported as being significantly associated with oxaliplatin-induced peripheral sensory neuropathy.

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A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1)

Treatment with abirterone acetate, in combination with prednisone, is beneficial for some patients with molecular apocrine tumours.

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A Phase 1 Dose-Escalation Study of Apatorsen (OGX-427), an Antisense Inhibitor Targeting Heat Shock Protein 27 (Hsp27), in Patients with Castration Resistant Prostate Cancer and Other Advanced Cancers

Apatorsen is an antisense inhibitor of heat shock protein 27 (Hsp27), a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways. A Phase 1 study was conducted in patients with CRPC and other cancers known to overexpress Hsp27. Apatorsen had an acceptable safety profile and a MTD was not defined. Clinical activity at doses ≥400 mg was suggested by effects on stable measurable disease, declines in PSA, other tumor markers, and CTCs.

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Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish Prospective Multicenter Study (GECMP-CCR)

Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival as compared to limited pulmonary resection. Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results.

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Response to Angiotensin Blockade with Irbesartan in a Patient with Metastatic Colorectal Cancer

As part of a personalized oncogenomics initiative whole genome and transcriptome sequencing was used to interrogate a mismatch repair-deficient tumour from a patient suffering from metastatic colorectal cancer resistant to standard chemotherapy and radiation. Analysis of gene expression outliers identified high expression of the activating protein-1 (AP-1) transcriptional complex, indicating potential oncogene addiction. Based on this analysis, the possibility of treatment targeting the renin–angiotensin system upstream of the AP-1 complex was raised and a trial of the angiotensin receptor blocker irbesartan was initiated. The patient's disease exhibited a profound and durable response to this treatment indicating a new potential therapeutic axis for patients with similar genomic indications.

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