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    MeSH term: Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Senkomago V, Henley SJ, Thomas CC, et al.
Human Papillomavirus-Attributable Cancers - United States, 2012-2016.
MMWR Morb Mortal Wkly Rep. 2019; 68(33):724-728 [PubMed] Related Publications
Human papillomavirus (HPV) causes nearly all cervical cancers and some cancers of the vagina, vulva, penis, anus, and oropharynx (1).* Most HPV infections are asymptomatic and clear spontaneously within 1 to 2 years; however, persistent infection with oncogenic HPV types can lead to development of precancer or cancer (2). In the United States, the 9-valent HPV vaccine (9vHPV) is available to protect against oncogenic HPV types 16, 18, 31, 33, 45, 52, and 58 as well as nononcogenic types 6 and 11 that cause genital warts. CDC analyzed data from the U.S. Cancer Statistics (USCS)

Chari A, Vogl DT, Gavriatopoulou M, et al.
Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma.
N Engl J Med. 2019; 381(8):727-738 [PubMed] Related Publications
BACKGROUND: Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.
METHODS: We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point.
RESULTS: A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients.
CONCLUSIONS: Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).

Sun S, Hu Z, Huang S, et al.
REG4 is an indicator for KRAS mutant lung adenocarcinoma with TTF-1 low expression.
J Cancer Res Clin Oncol. 2019; 145(9):2273-2283 [PubMed] Related Publications
OBJECTIVES: Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation plus TTF-1 low expression (KC subgroup). The aim of this study was to identify valuable biomarkers by searching the candidate molecules that contribute to lung adenocarcinoma pathogenesis, especially KC subtype.
MATERIALS AND METHODS: We analyzed the publicly available database and identified the candidate REG4 using the E-GEOD-31210 dataset, and then confirmed by TCGA dataset. In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. Functional studies and RNA sequencing were performed after silencing the REG4 expression.
RESULTS: REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutant lung adenocarcinoma with low expression of TTF-1 (KC subtype). The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. Further in vitro and in vivo functional assays revealed silencing REG4 expression significantly reduces cancer cell proliferation and tumorigenesis. Moreover, RNA sequencing and GSEA analysis displayed that REG4 knockdown might induce cell cycle arrest by regulating G2/M checkpoint and E2F targets.
CONCLUSION: Our results indicate that REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanisms of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.

Yousefnia S, Ghaedi K, Seyed Forootan F, Nasr Esfahani MH
Characterization of the stemness potency of
Tumour Biol. 2019; 41(8):1010428319869101 [PubMed] Related Publications
Stemness phenotype mammospheres established from cell lines and tissues taken from autopsy can be used to test and to identify the most sensitive drugs for chemotherapy. Therefore, the aim of the present study was isolation and characterization of cancer stem cells derived from MCF7, MDA-MB231, and SKBR3 breast cancer cell lines to demonstrate the stemness phenotypes of mammospheres generated for further their applications in therapeutic approaches. In this study, two luminal subtypes of cell lines, MCF7 and SKBR3 and a basal subtype cell line, MDA-MB-231, were chosen. Mammosphere culturing was implemented for breast cancer stem cells isolation and mammosphere formation efficiency. At the next step, CD44+/CD24- cell ratio,

Haines K, Huang GS
Precision Therapy for Aggressive Endometrial Cancer by Reactivation of Protein Phosphatase 2A.
Cancer Res. 2019; 79(16):4009-4010 [PubMed] Related Publications
Critically important to reducing uterine cancer mortality is the development of more effective therapy for aggressive endometrial cancers, including uterine serous cancer and uterine carcinosarcoma, which together account for over half of deaths due to endometrial cancer. About one-third of these aggressive endometrial cancers harbor mutations in the protein phosphatase 2A (PP2A) Aα scaffold subunit encoded by

Yamasaki M, Funaishi K, Kawamoto K, et al.
Platinum-doublet chemotherapy followed by pembrolizumab therapy for lung cancer with lymphangitis carcinomatosa mimicking interstitial pneumonitis: A case report.
Medicine (Baltimore). 2019; 98(33):e16834 [PubMed] Related Publications
RATIONALE: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs.
PATIENT CONCERNS AND DIAGNOSES: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa.
INTERVENTIONS AND OUTCOMES: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months.
LESSONS: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.

Zhang R, Chen J, Zheng H, et al.
Effects of medium chain triglycerides on body fat distribution and adipocytokine levels in children with acute lymphoblastic leukemia under chemotherapy.
Medicine (Baltimore). 2019; 98(33):e16811 [PubMed] Related Publications
Glucocorticoids used to treat acute lymphoblastic leukemia (ALL) are associated with cytotoxicity and obesity. The aim of the study was to investigate the effects of high-proportion medium chain triglyceride (MCT) on body fat distribution and levels of leptin and adiponectin during chemotherapy of children with ALL.New-onset ALL children treated at the Guangzhou Women and Children's Medical Center between March 2016 and March 2017 were enrolled. Children were divided into the MCT and control groups. For the MCT group, high-proportion MCT nutrition preparation was added to the diet, while no MCT was added for the control group. The MCT group was further divided into subgroups A and B based on the amount of supplement. Waist circumference, hip circumference, waist-to-hip ratio, bone marrow concentrations of leptin and adiponectin, and leptin-to-adiponectin ratio were measured before and on days 19 and 46 of chemotherapy. Body weight and body mass index (BMI) were measured on admission and discharge.Waist circumference in the control group increased by day 46 (P = .047), but did not change in the MCT group. The BMI of the children in the control group was higher than those in the MCT group on admission (P = .003), but not different at discharge. No significant differences in hip circumference, leptin levels, adiponectin levels, and body weight were observed between the 2 groups.This preliminary study suggests that short-term supplementation of high-proportion MCT nutrition preparation may help reduce the centripetal distribution of adipose induced by the application of glucocorticoids in children with ALL. This will have to be confirmed in future studies.

Yang HB, Kim HY, Jung SE, et al.
Pediatric minimally invasive surgery for malignant abdominal tumor: Single center experience.
Medicine (Baltimore). 2019; 98(33):e16776 [PubMed] Related Publications
This study examined the safety and usefulness of minimally invasive surgery (MIS) for malignant abdominal tumors in pediatric patients and analyzed the factors affecting the resection margin, operative time, and hospital stay of neuroblastoma (NBL) patients.We retrospectively reviewed data of pediatric patients who underwent MIS for malignant abdominal tumors from January 2011 to June 2017 at the Seoul National University Children's Hospital. Sex; age at operation; diagnosis; tumor location; operation-related data, such as operation time and transfusion; and follow-up data were reviewed. We divided patients into an excision group and a biopsy group. Detailed pathologic data were reviewed to analyze factors affecting the resection margin of NBL. Median value and range were calculated for all continuous variables. Mann-Whitney test and χ test were used as appropriate. P values of <.05 were considered significant.Thirty-four pediatric patients were included; 21 were boys. The median age was 4 (0.2-18) years. The most common diagnosis was NBL (17 patients; 50.0%). Three patients each were diagnosed with lymphoma, solid pseudopapillary tumor of the pancreas, and teratoma. The median tumor size was 3.4 (0.5-10.2) cm. The median operation time was 108 (55-290) minutes, and the median hospital stay was 5 (2-11) days. The number of conversions to open surgery was 4. There were no postoperative complications or mortality. There were 18 patients in the excision group and 16 in the biopsy group. Diagnosis and the number of patients receiving preoperative chemotherapy differed between the 2 groups. R0 resection of NBL was significantly higher in patients with stage 1 disease and those aged >2 years. There were no clinical factors influencing operative time or hospital stay.MIS was feasible and safe in pediatric patients with malignant abdominal tumors. R0 resection of NBL was related to age and stage.

Erol T, İmamoğlu NE, Aydin B, et al.
Primary tumor resection for initially staged IV breast cancer: An emphasis on programmed death-ligand 1 expression, promoter methylation status, and survival.
Medicine (Baltimore). 2019; 98(33):e16773 [PubMed] Related Publications
Conventional therapy modalities for advanced breast cancer are problematic, whereas checkpoint blockade immunotherapy has been considered as a promising approach. This study aims to determine programmed death-ligand 1 (PD-L1) expression and methylation status of PD-L1 promoter in primary tumor tissue and metastatic foci of patients with stage IV breast cancer.Clinicopathological data and survival rates of 57 breast cancer patients, who were initially staged IV, and operated for intact tumors, were retrospectively analyzed. Immunohistochemical analysis of PD-L1 using 57 primary tumors, 33 paired metastatic lymph nodes, and 14 paired distant metastases was performed. Additionally, the methylation rate of the PD-L1 gene promoter region was determined with real-time polymerase chain reaction (PCR) analysis in 38 samples.Overall PD-L1 expression in primary tumors was 23.1% (12/52). PD-L1 positivity was reduced in lymph nodes by 15.2% (5/33) and in distant metastases by 21.4% (3/14). PD-L1 expression diverged between primary and metastatic foci in a subset of cases (18.2% for lymph node and 33.3% for distant metastasis). In general, the PD-L1 promoter was not methylated, and mean methylation rates were low (min. 0%-max. 21%). We observed no correlation between PD-L1 expression, promoter methylation, and survival.Neither the expression nor the methylation status of PD-L1 in patients, who were presented with stage IV breast cancer and operated for an intact primary tumor, had a statistically significant relation with survival. Discordance in PD-L1 expression between primary tumor and metastasis should be considered during pathological and clinical management of patients who would undergo checkpoint blockade therapy.

Lin CY, Chang CC, Su PL, et al.
Brain MRI imaging characteristics predict treatment response and outcome in patients with de novo brain metastasis of EGFR-mutated NSCLC.
Medicine (Baltimore). 2019; 98(33):e16766 [PubMed] Related Publications
Patients with non-small cell lung cancer (NSCLC) and de novo brain metastasis (BM) have poor prognosis. We aim to investigate the characteristic of brain magnetic resonance (MR) imaging and the association with the treatment response of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer with BM.EGFR-mutated NSCLC patients with BM from October 2013 to December 2017 in a tertiary referral center were retrospectively analyzed. Patient's age, sex, cell type, EGFR mutation status, treatment, and characteristics of BM were collected. Survival analysis was performed using Kaplan-Meier method. The efficacy of different EGFR-TKIs were also analyzed.Among the 257 eligible patients, 144 patients with Exon 19 deletion or Exon 21 L858R were included for analysis. The erlotinib group had the best progression free survival (PFS) (median PFS 13 months, P = .04). The overall survival (OS) revealed no significant difference between three EGFR-TKI groups. Brain MR imaging features including tumor necrosis, rim enhancement and specific tumor locations (frontal lobe, putamen or cerebellum) were factors associated with poor prognosis. Patients with poor prognostic imaging features, the high-risk group, who received erlotinib had the best PFS (median PFS 12 months, P < .001). However, the OS revealed no significant difference between 3 EGFR-TKI groups. The low risk group patients had similar PFS and OS treated with three different EGFR-TKIs.In NSCLC patients with common EGFR mutation and de novo BM, those with poor prognostic brain MR characteristics, erlotinib provided better PFS than afatinib or gefitinib.

Liu CJ, Fang KH, Chang CC, et al.
Application of "parachute" technique for free flap reconstruction in advanced tongue cancer after ablation without lip-jaw splitting: A retrospective case study.
Medicine (Baltimore). 2019; 98(33):e16728 [PubMed] Related Publications
The hemi or subtotal/total glossectomy is usually approached by lip-jaw splitting procedure for advanced tongue cancer ablation. This highly invasive procedure can cause facial disfiguration, bone malunion, and osteoradionecrosis. The aim of this study is to compare the surgical outcome in free flap tongue reconstruction between novel parachute technique in an intact jaw and the conventional lip-jaw splitting procedure after tongue cancer ablation.In this study, parachute technique was adopted for free flap inset in patients without mandibulotomy. We retrospectively reviewed patients who have received primary advanced tongue cancer resection and free flap reconstruction during April, 2008 to January, 2015. Patients were divided into 2 groups. Group A was undergoing parachute technique without lip-jaw splitting. We sutured all the strings through the edges of defect in the first step and through the matching points of flap margin in the second step from outside the oral cavity. Then, the strings were pulled and the flap was parachuted down on the defects after all the matching points were tied together. In group B, the patients received conventional lip-jaw splitting procedure. Student t test was used for results analysis.There were 15 patients (n = 15) in group A and 15 patients (n = 15) in group B. In the patients receiving parachute technique, operation time showed 34 minutes (P = .49) shorter, hospital stay showed 4 days (P = .32) shorter, and the infection rate of surgical site showed 6.6% (P = .64) less than with conventional technique. The survival rates of the flaps were both 100% without revision.The parachute technique is an effective and more accessible method for free flap setting in cases of tongue reconstruction without lip-jaw splitting, and provides patients with better aesthetic appearance.

Zhao R, Jia T, Qiao B, et al.
Nomogram predicting long-term overall survival and cancer-specific survival of lip carcinoma patients based on the SEER database: A retrospective case-control study.
Medicine (Baltimore). 2019; 98(33):e16727 [PubMed] Related Publications
Our study was designed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of lip carcinoma patients.A search of the Surveillance, Epidemiology, and End Results (SEER) database provided us with detailed clinical data of the 1780 lip carcinoma patients. On the basis of the credible random split-sample method, the 1780 patients were placed into 2 groups, with 890 patients in the modeling group and 890 patients in the counterpart's group (proportion = 1:1). By employing Kaplan-Meier univariate and Cox multivariate survival analyses based on the modeling cohort, the nomograms were developed and then used to divide the modeling cohort into low-risk cohort and high-risk cohort. The survival rates of the 2 groups were calculated. Internal and external evaluation of nomogram accuracy was performed by the concordance index (C-index) and calibration curves.With regard to 5- and 8-year OS and CSS, the C-indexes of internal validation were 0.762 and 0.787, whereas those of external validation reached 0.772 and 0.818, respectively. All the C-indexes were higher than 0.7. The survival curves of the low-risk cohort were obviously better than those of the high-risk cohort.Credible nomograms have been established based on the SEER large-sample population research. We believe these nomograms can contribute to the design of treatment plans and evaluations of individual prognosis.

Yuan GL, Liang LZ, Zhang ZF, et al.
Hospitalization costs of treating colorectal cancer in China: A retrospective analysis.
Medicine (Baltimore). 2019; 98(33):e16718 [PubMed] Related Publications
BACKGROUND: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China.
METHODS: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer.
RESULTS: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ± 13.28 years; male: 59.46%; mean age: 61.80 ± 13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001).
CONCLUSION: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

Xu P, Xia T, Ling Y, Chen B
MiRNAs with prognostic significance in multiple myeloma: A systemic review and meta-analysis.
Medicine (Baltimore). 2019; 98(33):e16711 [PubMed] Related Publications
BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM.
METHODS: A meta-analysis was performed to estimate the pooled hazard ratios and their corresponding 95% confidence intervals for the associations between levels of miRNA expression (predictive factors) and outcomes in patients with MM. We systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases (final search conducted January 1, 2018) to identify eligible studies. Eligible studies were included by certain inclusion and exclusion criteria, whose quality was assessed by Newcastle-Ottawa Scale.
RESULTS: After performing the literature search and review, 10 relevant studies, including 1214 cases, were identified. The results of our meta-analysis revealed that upregulated miR-92a level and downregulated miR-16, miR-25, miR-744, miR-15a, let-7e, and miR-19b expression were associated with poor prognosis in MM.
CONCLUSIONS: This study identified miRNAs could serve as potential prognostic biomarkers in MM. Given the limited research available, the clinical application of these findings has yet to be verified.

Hou B, Liang C
Sporadic renal hybrid oncocytic/chromophobe tumor in a young man: A case report.
Medicine (Baltimore). 2019; 98(33):e16641 [PubMed] Related Publications
RATIONALE: Hybrid oncocytic/chromophobe tumor (HOCT) is defined as tumor composed of renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Sporadic HOCT is extremely rare, the preoperative diagnosis is difficult, and no guidelines for clinical therapy. We report a case who is the youngest male patient of sporadic HOCT in the world, review the previously reported cases, and share the clinical features, diagnosis, treatment, and prognosis of HOCT.
PATIENT CONCERNS: A 30-year-old man was admitted with the complaints of incidental right renal tumor detected by abdominal ultrasound. He had no complaints of urological symptoms, abdominal pain, osphyalgia, and hematuria. Abdominal contrast-enhanced computed tomography revealed an 85 mm × 80 mm × 80 mm unilateral and solid renal mass, and no findings of metastases.
DIAGNOSIS: The preoperative diagnosis was right renal tumor.
INTERVENTIONS: Laparoscopic right radical nephrectomy was performed.
OUTCOMES: Histopathology demonstrated a mixture of cells with the morphologic features of those seen in CHRCC and RO. The patient was final diagnosed as sporadic HOCT. After follow-up of 14 months, the patient had no complaints and evidence of disease recurrence.
LESSONS: Sporadic HOCT is extremely rare. It is possible that core biopsy could improve diagnostic accuracy. Laparoscopic radical nephrectomy or nephron sparing surgery should be considered the clinical therapy of the sporadic HOCT patients. The clinical behavior of HOCT is still entirely uncertain and should be proved by studies with available long follow-up.

Wong CK, Chan SC, Ng SH, et al.
Textural features on 18F-FDG PET/CT and dynamic contrast-enhanced MR imaging for predicting treatment response and survival of patients with hypopharyngeal carcinoma.
Medicine (Baltimore). 2019; 98(33):e16608 [PubMed] Related Publications
The utility of multimodality molecular imaging for predicting treatment response and survival of patients with hypopharyngeal carcinoma remains unclear. Here, we sought to investigate whether the combination of different molecular imaging parameters may improve outcome prediction in this patient group.Patients with pathologically proven hypopharyngeal carcinoma scheduled to undergo chemoradiotherapy (CRT) were deemed eligible. Besides clinical data, parameters obtained from pretreatment 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT), dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and diffusion-weighted MRI were analyzed in relation to treatment response, recurrence-free survival (RFS), and overall survival (OS).A total of 61 patients with advanced-stage disease were examined. After CRT, 36% of the patients did not achieve a complete response. Total lesion glycolysis (TLG) and texture feature entropy were found to predict treatment response. The transfer constant (K), TLG, and entropy were associated with RFS, whereas K, blood plasma volume (Vp), standardized uptake value (SUV), and entropy were predictors of OS. Different scoring systems based on the sum of PET- or MRI-derived prognosticators enabled patient stratification into distinct prognostic groups (P <.0001). The complete response rate of patients with a score of 2 was significantly lower than those of patients with a score 1 or 0 (14.7% vs 58.9% vs 75.7%, respectively, P = .007, respectively). The combination of PET- and DCE-MRI-derived independent risk factors allowed a better survival stratification than the TNM staging system (P <.0001 vs .691, respectively).Texture features on F-FDG PET/CT and DCE-MRI are clinically useful to predict treatment response and survival in patients with hypopharyngeal carcinoma. Their combined use in prognostic scoring systems may help these patients benefit from tailored treatment and obtain better oncological results.

Matsuda S, Yoshimura H, Yoshida H, et al.
Ossifying fibroma in the mandibular angle mimicking metastatic clear cell renal cell carcinoma: A case report.
Medicine (Baltimore). 2019; 98(33):e16595 [PubMed] Related Publications
RATIONALE: Ossifying fibroma is benign fibro-osseous neoplasm. The authors report a case of ossifying fibroma in the mandibular angle suspected as metastasis of clear cell renal cell carcinoma.
PATIENT CONCERNS: A 74-year-old man presented to the primary hospital complaining of frequent urination. A tumor in the left kidney was detected via an abdominal computed tomography scan. The patient then visited the Department of Urology at our hospital.
DIAGNOSES: According to whole-body imaging examinations, the patient was suspected of having renal cancer with mandibular metastasis. Also, a cystic lesion of the maxilla was revealed.
INTERVENTIONS: Left nephrectomy was performed by urologists, and the patient was diagnosed with clear cell renal cell carcinoma of the left kidney. Approximately 1 month later, resection with a safety margin of the mandibular lesion and removal of the maxillary lesion were performed by oral and maxillofacial surgeons.
OUTCOMES: The patient was diagnosed with ossifying fibroma of the mandible and an odontogenic keratocyst of the maxilla via a histopathological examination. Eighteen months have passed since the operation without clinical and imaging findings associated with recurrence.
LESSONS: Ossifying fibroma in the mandibular angle of elderly patients is extremely rare. Surgeons should consider the possibility of metastasis when osteolytic lesions of the jaw are found in patients with cancer.

Husby A, Wohlfahrt J, Melbye M
Pregnancy duration and endometrial cancer risk: nationwide cohort study.
BMJ. 2019; 366:l4693 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To explore the association between pregnancy duration and risk of endometrial cancer.
DESIGN: Nationwide register based cohort study.
SETTING: Denmark.
PARTICIPANTS: All Danish women born from 1935 to 2002.
MAIN OUTCOME MEASURES: Relative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression.
RESULTS: Among 2 311 332 Danish women with 3 947 650 pregnancies, 6743 women developed endometrial cancer during 57 347 622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results.
CONCLUSIONS: The risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.

Riyahi N, Safaroghli-Azar A, Sheikh-Zeineddini N, et al.
Synergistic Effects of PI3K and c-Myc Co-targeting in Acute Leukemia: Shedding New Light on Resistance to Selective PI3K-δ Inhibitor CAL-101.
Cancer Invest. 2019; 37(7):311-324 [PubMed] Related Publications
Enthusiasms into the application of PI3K-δ inhibitor CAL-101 has been muted due to the over-activation of compensatory molecules. Our results delineated that c-Myc suppression using 10058-F4 enhanced CAL-101 cytotoxicity in less sensitive cells through different mechanisms based on p53 status; while CAL-101-plus-10058-F4 induced G1 arrest in wild-type p53-expressing leukemic cells, no conspicuous increase in G1 was noted in U937 cells harboring mutant p53. Conclusively, this study shed lights on the role of c-Myc oncoprotein in acute leukemia cells sensitivity to PI3K inhibitor and outlined that the combination of c-Myc inhibitor and CAL-101 may be a promising therapeutic approach in leukemia.

Guo Y
Clinical significance of serum MicroRNA-203 in patients with acute myeloid leukemia.
Bioengineered. 2019; 10(1):345-352 [PubMed] Related Publications
This study aimed to detect serum miR-203 expression levels in AML and explore its potential clinical significance. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure the serum miR-203 levels in 134 patients with AML and 70 healthy controls. The results demonstrated that serum miR-203 expression was significantly reduced in AML patients compared with healthy controls. Receiver operating characteristic curve (ROC) analysis revealed miR-203 could distinguish AML cases from normal controls. Low serum miR-203 levels were associated with worse clinical features, as well as poorer overall survival and relapse free survival of AML patients. Moreover, multivariate analysis confirmed low serum miR-203 expression to be an independent unfavorable prognostic predictor for AML. The bioinformatics analysis showed that the downstream genes and pathways of miR-203 was closely associated with tumorigenesis. Downregulation of miR-203 in AML cell lines upregulated the expression levels of oncogenic promoters such as CREB1, SRC and HDAC1. Thus, these findings demonstrated that serum miR-203 might be a promising biomarker for the diagnosis and prognosis of AML.

Lovasik BP, Wang VL, Point du Jour KS, et al.
Visceral Kaposi Sarcoma Presenting as Small Bowel Intussusception: A Rare Presentation and Call to Action.
Am Surg. 2019; 85(7):778-780 [PubMed] Related Publications
Surgical emergencies related to visceral involvement of Kaposi sarcoma (KS) are rare complications of the disease. In this report, we describe a case of visceral KS causing small bowel intussusception in a young, previously undiagnosed human immunodeficiency virus (HIV)-positive patient. Southern surgeons should be particularly attentive to HIV/AIDS-related disease as a cause of surgical pathology, particularly in the southeast, and can play a significant advocacy role for improved access to HIV/AIDS diagnostic and treatment services.

Wang M, Huang J, Chagpar AB
Can I Keep My Nipple? Factors Influencing the Surgical Decision between Skin-Sparing and Nipple-Sparing Mastectomy.
Am Surg. 2019; 85(7):768-771 [PubMed] Related Publications
Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) are well accepted in the management of breast cancer. Factors that influence the decision of choosing one of these techniques over the other, however, remain to be well elucidated. From January 2010 to December 2017, 734 patients at our institution underwent one of these two procedures. Factors differentiating these patient cohorts were compared. In this study, 196 (26.7%) underwent NSM and 538 (73.3%) underwent SSM. The median age of patients at the time of surgery was 50 years (range, 22-78 years). On multivariate analysis, younger patient age, insurance type, BRCA+ mutation status, smaller breast size (by weight), and those who did not undergo neoadjuvant chemotherapy were more likely to undergo NSM. Surgeon also was an independent predictor of whether patients had NSM or SSM. There may be many factors that play into the decision to pursue NSM

Ramonell KM, Saunders ND, Sarmiento J, et al.
Avoiding Pitfalls in Insulinomas by Preoperative Localization with a Dual Imaging Approach.
Am Surg. 2019; 85(7):742-746 [PubMed] Related Publications
Insulinomas are rare endocrine malignancies of the pancreas that require surgical resection but can be difficult to localize preoperatively. We sought to review and improve the accuracy of preoperative localization techniques at our institution. We retrospectively reviewed all insulinomas that underwent resection at our institution between 1998 and 2016. Localization techniques include selective arterial calcium stimulation (CaStim), CT, MRI, angiography, and somatostatin receptor scintigraphy. Thirty-eight patients had pathologically proven insulinomas on surgical resection. Localization accuracies of CaStim, CT, and MRI were 89 per cent (31/35), 67 per cent (22/33), and 46 per cent (11/24), respectively. When compared with CT alone and CaStim alone, the combination of these two modalities resulted in 100 per cent preoperative localization (30/30), whereas the use of CaStim alone resulted in 80 per cent (4/5) localization and the use of CT alone resulted in 66 per cent (2/3) localization. Four of our patients had both negative CT and MRI. Among these patients, CaStim was 100 per cent localizing and the only positive modality for these patients. These data confirm that CaStim is accurate in preoperatively identifying single and multiple insulinomas; and when combined with CT, this accuracy is increased to 100 per cent. Based on these data, we propose that a dual imaging approach is a superior means of preoperative localization.

Seawell J, Sciarretta JD, Pahlkotter M, et al.
The Understated Malignancy Potential of Nonoperative Acute Appendicitis.
Am Surg. 2019; 85(7):712-716 [PubMed] Related Publications
Cancer of the appendix is rare and is most commonly found incidentally on pathology after an appendectomy for uncomplicated appendicitis (UA). The medical management alternative with antibiotics and observation remains an ongoing debate. The purpose of our study was to develop modern epidemiological data for adult patients completing an appendectomy for UA secondary to an appendiceal neoplasm (AN). ACS-NSQIP database was queried (2005-2016) to identify patients completing an appendectomy. Cohorts of patients who were diagnosed with UA and an AN were included in the study. Relevant perioperative clinical and outcomes data were collected. Type of AN, surgical procedure, and mortality were analyzed. A total of 239,615 UA patients were identified, of whom 2,773 (1.2%) met the inclusion criteria of AN. Patients with AN were predominantly white (79.5%), with a mean age of 54.5 ± 15.9 years, and 54.6 per cent were females. AN pathology findings included malignant neoplasm (64.5%), malignant carcinoid (17.3%), benign carcinoid (9.3%), and benign neoplasm (8.8%). The overall reported incidence was 1.2 per cent and the mortality rate was 0.7 per cent. Our study emphasizes surgical intervention in adult UA maintains a 1 per cent incidence of AN, and treatment with antibiotics alone will presumably lead to a delay in surgical treatment and progression of disease.

White RL, Palmer PP, Trufan SJ, Sarma D
Does Neoadjuvant Chemotherapy for Breast Cancer Affect Lymph Node Harvest Rates?
Am Surg. 2019; 85(7):690-694 [PubMed] Related Publications
Some authors report that patients receiving neoadjuvant chemotherapy have fewer lymph nodes harvested during axillary dissection and more dissections with < 10 nodes compared with patients who undergo surgery initially. We sought to determine whether there was a difference between these patient groups in terms of number of nodes harvested and number of dissections with < 10 nodes. Retrospective review of 258 patients diagnosed with breast cancer who underwent an axillary lymph node dissection between July 1, 2015, and December 31, 2017 was performed. Chi-squared test was used to assess differences between patient groups. Of 258 patients undergoing dissection, 48 per cent received neoadjuvant chemotherapy; 52 per cent underwent surgery as first therapeutic intervention. Mean number of nodes resected; 14.3 + 6.3 for patients with no prior chemotherapy

Hadj-Ahmed M, Ghali RM, Bouaziz H, et al.
Transforming growth factor beta 1 polymorphisms and haplotypes associated with breast cancer susceptibility: A case-control study in Tunisian women.
Tumour Biol. 2019; 41(8):1010428319869096 [PubMed] Related Publications
Variable association of transforming growth factor beta 1 (TGFβ1) in breast cancer (BC) pathogenesis was documented, and the contribution of specific

Liu J, Liu C, Zhang X, et al.
Anticancer sulfonamide hybrids that inhibit bladder cancer cells growth and migration as tubulin polymerisation inhibitors.
J Enzyme Inhib Med Chem. 2019; 34(1):1380-1387 [PubMed] Related Publications
Novel sulfonamide-dithiocarbamate hybrids were designed and synthesised via the molecular hybridisation strategy. Among them, compound

Shuwen H, Miao D, Quan Q, et al.
Protective effect of the "food-microorganism-SCFAs" axis on colorectal cancer: from basic research to practical application.
J Cancer Res Clin Oncol. 2019; 145(9):2169-2197 [PubMed] Related Publications
BACKGROUND: Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC).
AIMS: This study aims to elucidate the "food-microorganism-SCFAs" axis and to provide guidance for prevention and intervention in CRC.
METHODS: The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening.
RESULTS: The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The "food-microorganism-SCFAs" axis was constructed by summarizing the pertinent literature.
CONCLUSIONS: This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.

Pak S, Kim W, Kim Y, et al.
Dihydrotestosterone promotes kidney cancer cell proliferation by activating the STAT5 pathway via androgen and glucocorticoid receptors.
J Cancer Res Clin Oncol. 2019; 145(9):2293-2301 [PubMed] Related Publications
PURPOSE: Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status.
METHODS: Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation.
RESULTS: DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone.
CONCLUSION: DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.

Kucharska E, Kucharska A, Sieroń A, et al.
Modern methods of treatment in palliative care.
Wiad Lek. 2019; 72(7):1229-1235 [PubMed] Related Publications
The palliative care patient is definitely a unique type of patient. Due to the complexity of the symptoms requires a holistic therapeutic approach. Modern methods of treatment in palliative and hospice care underline an important role of physio, kinesiotherapy and pharmacological treatment coexistence. The rehabilitation reduces clinical symptoms, accompanying the basic disease and increases the quality of life of palliative patients and their families. It becomes an inseparable element of treatment, both in outpatient care as well as in stationary care and home care. Due to the high dynamics onset of cancer in the group of geriatric patients there is a need for a broader analysis of the topic. The goal of palliative care is to achieve the best possible quality of life for patients and their families.

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