Inosine Triphosphate Pyrophosphohydrolase (ITPA) polymorphic sequence variants in adult hematological malignancy patients and possible association with mitochondrial DNA defects

Background: Inosine triphosphate pyrophosphohydrolase (ITPase) is a 'house-cleaning' enzyme that degrades non-canonical ('rogue') nucleotides. Complete deficiency is fatal in knockout mice, but a mutant polymorphism resulting in low enzyme activity with an accumulation of ITP and other non-canonical nucleotides, appears benign in humans. We hypothesised that reduced ITPase activity may cause acquired mitochondrial DNA (mtDNA) defects. Furthermore, we investigated whether accumulating mtDNA defects may then be a risk factor for cell transformation, in adult haematological malignancy (AHM). Methods: DNA was extracted from peripheral blood and bone marrow samples. Microarray-based sequencing of mtDNA was performed on 13 AHM patients confirmed as carrying the ITPA 94C>A mutation causing low ITPase activity, and 4 AHM patients with wildtype ITPA. The frequencies of ITPA 94C>A and IVS2+21A>C polymorphisms were studied from 85 available AHM patients. Results: ITPA 94C>A was associated with a significant increase in total heteroplasmic/homoplasmic mtDNA mutations (p<0.009) compared with wildtype ITPA, following exclusion of haplogroup variants. This suggested that low ITPase activity may induce mitochondrial abnormalities. Compared to the normal population, frequencies for the 94C>A and IVS2+21A>C mutant alleles among the AHM patients were higher for myelodyplastic syndrome (MDS) - but below significance; were approximately equivalent for chronic lymphoblastic leukemia; and were lower for acute myeloid leukemia. Conclusions: This study invokes a new paradigm for the evolution of MDS, where nucleotide imbalances produced by defects in 'house-cleaning' genes may induce mitochondrial dysfunction, compromising cell integrity. It supports recent studies which point towards an important role for ITPase in cellular surveillance of rogue nucleotides.

via Journal of Hematology & Oncology

Family history linked to colorectal cancer survival

A family history of colorectal cancer is associated with an increased, rather than decreased, chance for survival after diagnosis, UK researchers have found.

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Physical symptoms a priority in advanced breast cancer

Women with advanced breast cancer adapt to their emotional and spiritual symptoms despite reporting poor physical functioning and pain compared with women who have local or regional disease, indicate US study results.

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Induction chemotherapy cuts metastasis risk in resectable HNSCC

Induction chemotherapy offers significant benefits in the management of resectable squamous cell carcinoma of the head and neck, Chinese researchers believe.

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The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells

Background: Liver cancer is one of the most frequent cancers in the world. Targeted therapy of cancer with specific inhibitors is developing and has shown promising antitumor efficacy. CCI-779 (temsirolimus), a specific inhibitor of mTOR (mammalian target of rapamycin), can block the mTOR signaling pathway. Here, we systematically examined the expression of mTOR and its downstream targets liver cancer cells and normal liver cells, and then investigated inhibitory effects of CCI-779 on mTOR signaling pathway and its role in regulating liver cancer cell growth. Methods: The expression of mTOR and its downstream targets in Bel-7402 liver cancer cells and HL-7702 normal liver cells were examined by western blot. The mTOR specific inhibitor (CCI-779) was used to treat Bel-7402 cells to identify its effects on Bel-7402 cell growth and activity of mTOR signaling pathway in vitro. Cell viability tests were performed after the treatment of CCI-779. Western blot was applied to assess the changes of mTOR pathway and flow cytometry was used to analyze cell cycle of Bel-7402 cells after the treatment of CCI-779. Results: mTOR, p70S6K, S6, and 4EBP1 were overexpressed in Bel-7402 cells compared with HL-7702 cells. Bel-7402 cells were sensitive to CCI-779. The survival rate of the cells treated with CCI-779 over 0.312 muM was significantly different compared with that of control (P < 0.05). CCI-779 inhibited the phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser240/244), and 4EBP1 (Thr37/46) in different grades and the expressions of p70S6K, S6, and 4EBP1. As a result, CCI-779 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape. Conclusions: Taken together, these data showed that CCI-779 can inhibit mTOR signaling and proliferation in Bel-7402 liver cancer cells in vitro. It offers a therapeutic intervention through inhibition of mTOR as a potential strategy for liver cancer.

via Cancer Cell International

Anal intraepithelial neoplasia best treated by electrocauterization

Electrocauterization is better than topical treatments for treating anal intraepithelial neoplasia in HIV-positive men who have sex with men, Dutch study findings suggest.

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Circulating tumor DNA effective biomarker in breast cancer

Circulating tumor DNA seems to be an effective biomarker for monitoring metastatic breast cancer, say researchers.

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Active surveillance an option for some low risk prostate cancer patients

Active surveillance of individuals with very-low-risk prostate cancer who are also on 5 α-reductase inhibitor therapy for benign prostatic hyperplasia seems to be a safe therapeutic option, say researchers.

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Routine planning results in patients' preferred place of death

Conducting advanced care planning during the last year of life is not only feasible but results in three-quarters of patients dying in their preferred location, show UK study results.

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Targeting p53 by small molecules in hematological malignancies

p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target. A breakthrough in cancer research came from the discovery of the drugs which are capable of reactivating p53 function. Most anti-cancer agents, from traditional chemo- and radiation therapies to more recently developed non-peptide small molecules exert their effects by enhancing the anti-proliferative effects of p53. Small molecules such as nutlin, RITA, and PRIMA-1 that can activate p53 have shown their anti-tumor activities in different types of hematological malignancies. Importantly, nutlin and PRIMA-1 have successfully reached the stage of phase I/II clinical trials in at least one type of hematological cancer. Thus, the pharmacological activation of p53 by these small molecules has a major clinical impact on prognostic use and targeted drug design. In the current review, we present the recent achievements in p53 research using small molecules in hematological malignancies. Anticancer activity of different classes of compounds targeting the p53 signaling pathway and their mechanism of action are discussed. In addition, we discuss how p53 tumor suppressor protein holds promise as a drug target for recent and future novel therapies in these diseases.

via Journal of Hematology & Oncology

Association of BDNF and BMPR1A with clinicopathologic parameters in benign and malignant gallbladder lesions

Background: Neurotrophic factors such as brain derived neurotrophic factor (BDNF) are synthesized in a variety of neural and non-neuronal cell types and regulate survival, proliferation and apoptosis. In addition, bone morphogenetic proteins (BMPs) inhibit the proliferation of pulmonary large carcinoma cells bone morphogenetic protein receptor, type IA (BMPR1A). Little is known about the expression of BDNF or BMPR1A in malignant gall bladder lesions. This study was to evaluate BDNF and BMPR1A expression and evaluate the clinicopathological significance in benign and malignant lesions of the gallbladder. Methods: The BDNF and BMPR1A expression of gallbladder adenocarcinoma, peritumoral tissues, adenoma, polyp and chronic cholecystitis were Immunohistochemically determined. Results: BDNF expression was significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenoma, polyps and chronic cholecystitis samples. However, BMPR1A expression was significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, adenomas, polyps and chronic cholecystitis tissues. The specimens with increased expression of BDNF in the benign lesions exhibited moderate- or severe-dysplasia of gallbladder epithelium. BDNF expression was significantly lower in well-differentiated adenocarcinomas with maximum tumor diameter <2 cm, no metastasis to lymph nodes, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma. BMPR1A expression were significantly higher in the well-differentiated adenocarcinoma with maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder. Univariate Kaplan-Meier analysis indicated increased expression of BDNF or decreased expression of BMPR1A was associated with decreased disease specific survival (DSS) rates. Similarly, multivariate Cox regression analysis showed increased expression of BDNF or decreased expression of BMPR1A are independent predictors of poor DSS rates in gallbladder adenocarcinoma. Conclusions: In gallbladder malignancies, the increased expression of BDNF and decreased expression of BMPR1A were associated with increased risk of metastasis, regional invasion and mortality. They might serve as novel indicators of gallbladder adenocarcinoma outcomes, which may prove valuable for the development of personalized therapeutic paradigms.

via World Journal of Surgical Oncology

Stem cell transplantation linked to suicide risk

The risk for suicidal and accidental death may be elevated in patients who undergo hematopoietic stem cell transplantation, research suggests.

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Mifepristone improves chemo-radiation response in glioblastoma xenografts

Background: We have investigated the ability of Mifepristone, an anti-progestin and anti-glucocorticoid drug, to modulate the antitumor effect of current standard clinical treatment in glioblastoma xenografts. Methods: The effect of radiation alone or combined with Mifepristone and Temozolamide was evaluated on tumor growth in glioblastoma xenografts, both in terms of preferentially triggering tumor cell death and inhibiting angiogenesis. Tumor size was measured once a week using a caliper and tumor metabolic-activity was carried out by molecular imaging using a microPET/CT scanner. The effect of Mifepristone on the expression of angiogenic factors after concomitant radio-chemotherapy was determined using a quantitative real-time PCR analysis of VEGF gene expression. Results: The analysis of the data shows a significant antitumoral effect by the simultaneous administration of radiation-Mifepristone-Temozolamide in comparison with radiation alone or radiation-Temozolamide. Conclusion: Our results suggest that Mifepristone could improve the efficacy of chemo-radiotherapy in Glioblastoma. The addition of Mifepristone to standard radiation-Temozolamide therapy represents a potential approach as a chemo-radio-sensitizer in treating GBMs, which have very limited treatment options.

via Cancer Cell International

Genetic variants influencing bladder cancer discovered

Research published in Cancer sheds light on genetic variants that influence bladder cancer risk, recurrence, patient survival, and disease progression.

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Headaches portend neurovascular events in pediatric brain tumor patients

Severe recurrent headaches experienced by pediatric brain tumor survivors who received cranial radiation therapy is associated with a higher likelihood for a neurovascular event and thus signals neurovascular changes, shows a study.

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Childhood chemotherapy may raise renal cancer risk

Adults who survived childhood cancer may have an increased risk for renal carcinoma, suggests research published in the Journal of the National Cancer Institute.

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Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium

Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is the most common presentation of hereditary colorectal cancer (CRC), accounting for about 2--5% of all CRC cases. More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. In this commentary, we summarize the main clinicopathologic features of LS-related EC and propose universal screening for LS in individuals with endometrial cancer.

via Journal of Hematology & Oncology

Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis

Background: Macrophage migration inhibitory factor (MIF) is important in regulating cell proliferation and apoptosis in both normal and cancerous cells, and may be important in cancer progression and metastasis. In human non-small cell lung cancer (NSCLC), the underlying mechanisms responsible for MIF-dependent regulation of cellular proliferation, and cell death remain poorly appreciated. Methods: The human H460 lung cancer cell-line was treated with an optimally determined dose of 50 pmol/ml MIF siRNA, following which cell proliferation, cell cycle and apoptosis were analyzed. Additionally, known pathways of apoptosis including expression of Annexin-V, enhanced production of caspases-3 and -4 and expression of the Akt signaling protein were assessed in an attempt to provide insights into the signaling pathways involved in apoptosis following disruption of MIF expression. Results: Specific siRNA sequences markedly decreased MIF expression in H460 cells by 2 to 5-fold as compared with the negative control. Moreover, MIF miRNA dampened not only cellular proliferation, but increased the frequency of apoptotic cells as assessed by cell-surface Annexin-V expression. Entry of cells into apoptosis was partly dependent on enhanced production of caspases -3 and -4 while not affecting the expression of either caspase-8 or the Akt signaling pathway. Conclusions: In a model of NSCLC, knockdown of MIF mRNA expression dampened H460 proliferation by mechanisms partly dependent on entry of cells into apoptosis and enhanced production of caspase-3 and -4. MIF expression may thus be important in NSCLC progression. Targeting MIF may have clinical utility in the management of human lung cancer.

via Cancer Cell International

Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer?

Background: Decision making for adjuvant chemotherapy in stage III colon cancer is based on the TNM system. It is well known that prognosis worsens with higher pN classification, and several recent studies propose superiority of the lymph node ratio (ln ratio) to the TNM system. Therefore, we compared the prognosis of ln ratio to TNM system in our stage III colon cancer patients. Methods: A total of 939 patients underwent radical surgery for colorectal cancer between January 2000 and December 2009. From this pool of patients, 142 colon cancer stage III patients were identified and taken for this analysis. Using martingale residuals, this cohort could be separated into a group with a low ln ratio and one with a high ln ratio. These groups were compared to pN1 and pN2 of the TNM system. Results: For ln ratio, the cutoff was calculated at 0.2. There was a good prognosis of disease-free and cancer-related survival for the N-category of the TNM system as well as for the lymph node ratio. There was no statistical difference between using the N-category of the TNM system and the ln ratio. Conclusions: There might not be a benefit in using the lymph node ratio rather than the N category of the TNM system as long as the number of subgroups is not increased. In our consideration, there is no need to change the N categorization of the TNM system to the ln ratio.

via World Journal of Surgical Oncology

Complete remission by transarterial infusion with cisplatin for recurrent bile duct tumor thrombus of hepatocellular carcinoma: report of a case

Bile duct tumor thrombus (BDTT) of a hepatocellular carcinoma (HCC) is a rare entity which was found microscopically in 1 to 9.2% of the resected specimen.A 54-year-old male was found to have a 65-mm hepatocellular carcinoma in segment VI of the liver with a huge intrahepatic bile duct tumor thrombus. As the main trunk of the posterior segment branched from the left bile duct, the BDTT of the posterior branch extended to the common bile duct via the left bile duct. When the posterior segment was resected along with the left lobe, the estimated remnant liver volume was less than 30%. Therefore, the patient underwent extended posterior segmentectomy with choledochotomy and all of the BDTT was removed via the common bile duct.Three months later, his serum bilirubin (6.63 mg/dL) and des-gamma-carboxy prothrombin (410 ng/mL) were re-elevated due to recurrent BDTT. A well-enhanced BDTT was observed by computed tomography (CT) at the left bile duct. Transarterial chemotherapy with cisplatin was scheduled, followed by endoscopic retrograde bile duct drainage. After four sessions of this chemotherapy, the BDTT had vanished and the tumor marker was decreased to within the normal range. The patient was stably treated with this regimen and has remained recurrence-free for five years.

via World Journal of Surgical Oncology

Monitoring needs to be part of posaconazole use in cancer patients

A phase IV study assessing use of posaconazole in patients with hematologic cancer has identified a potentially serious drug–drug interaction with vincrinstine-based chemotherapy.

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Dispute over biannual breast screening

Screening women aged 50 to 74 years old for breast cancer every 2 years is as effective as annual screening but reduces the rate of false–positive diagnoses, conclude the authors of a US study.

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Thanks to Cancer Cell International reviewers (2012)

Contributing reviewersThe editor and editorial board of Cancer Cell International would like to thank Angela Panther for her continued hard work throughout 2012 in keeping the journal going as our managing editor. We take this opportunity in early 2013 to thank all our reviewers who contributed to the journal in Volume 12 (2012). Last year saw submissions double, which will mean that in 2013 we will certainly have many more articles to publish, and hopefully our Impact Factor will rise above 2.

via Cancer Cell International

Breast cancer after kidney transplantation: a single institution review

Background: Improvements in immunosuppression have resulted in long life expectancy of kidney transplants. Unfortunately, the incidence of post-transplant malignancy (PTM) is increasing. The aim of this study was to evaluate the nature and stage-specific prognosis of post-transplant breast cancer (PTBC) compared with breast cancer in the general population, and to suggest optimal treatment strategies. Methods: A prospectively collected database of 2,139 consecutive kidney transplant patients was reviewed;11 of the patients developed breast cancer. These 11 PTBC cases underwent operations between 1999 and 2011. Next, 2,554 breast cancer patients treated in the same period were reviewed. Kaplan--Meier curves and the log-rank test were used to assess stage-specific survival of breast cancer in our hospital. Results: In total, 142 cases experienced post-transplant malignancy (PTM; 6.6%) and 11 (0.5%) developed PTBC. No one required an adjusted dose of immunosuppressive agent. Two stage III patients died. For all breast cancer patients, 5-year survival by stage was 97.7% for stage I, 92.9% for stage II, 78.6% for stage III, and 49.9% for stage IV. The 5-year survival for expected stage III-specific survival was 66.7% and no significant statistical difference was seen compared to that of the total breast cancer patients (P = 0.213). Conclusions: The prognosis of PTBC was comparable to that of the general population. These results suggest that the use of immunosuppressants per se does not adversely affect breast cancer.

via World Journal of Surgical Oncology

Lymphatic invasion limited for predicting post-surgical RCC outcome

Microvascular and capillary-lymphatic invasion are both associated with patient outcome following nephrectomy for renal cell carcinoma, but their clinical utility may be limited for different reasons, say researchers.

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Metabolic factors increase risk for RCC

Researchers have found that high levels of several metabolic factors increase the risk for renal cell carcinoma, giving further impetus for attempting to control such factors, which have already been associated with other adverse health outcomes.

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Timing of cytoreductive nephrectomy impacts survival in mRCC

Patients with metastatic renal cell carcinoma who respond to tyrosine kinase inhibitor therapy may have better outcomes if they are treated with this targeted therapy before rather than after cytoreductive nephrectomy, study findings show.

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A retrospective study: platinum-based induction chemotherapy combined with gemcitabine or paclitaxel for stage IIB-IIIA central non-small-cell lung cancer

Background: Several encouraging phase III clinical trials have evaluated platinum-based induction chemotherapy against stage IIB-IIIA non-small-cell lung cancer (NSCLC). Chemotherapy efficacy was assessed using common regimens in this retrospective analysis. Methods: From 2007 to 2011, the clinical records of stage IIB-IIIA NSCLC patients undergoing surgery after neoadjuvant chemotherapy were reviewed. Gathered data were tested for significance and variables impacting survival were assessed by univariate and Cox regression analyses. Results: Overall, 84% of patients were male and 93% had central disease. Platinum-based chemotherapy protocols with gemcitabine or paclitaxel gave an overall response rate of 55% (45/82) and 6.1% pathological complete response (5/82). Clinical response was unassociated with regimen or histology, while more pneumonectomies were performed in the stable compared to partial response disease group (P =0.040). Postoperative mortality was 1.2% (1/82), and complications, unassociated with regimen or histology, were atelectasis (26.8%) and supraventricular arrhythmias (13.4%). Right-sided procedures appeared to increase the incidence of bronchopleural fistula (P =0.073). The median disease-free survival time was 18 months and median overall survival time was not reached. Disease-free survival rates at one, two, and three years were 54%, 47%, and 33%, while the overall survival rate was 73%, 69%, and 59%, respectively. Disease-free survival predictors were radiographic response and mediastinal lymphadenopathy before chemotherapy (P =0.012 and 0.002, respectively). Conclusions: Two cycles of platinum-based chemotherapy with gemcitabine or paclitaxel is efficacious for patients with stage IIB-IIIA central disease. Patients achieving clinical response had improved disease-free survival times, while those with mediastinal lymphadenopathy had a higher postoperative recurrence risk.

via World Journal of Surgical Oncology

Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review

We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.

via World Journal of Surgical Oncology

Colorectal cancer–constipation link dismissed

The findings of a meta-analysis fail to support the common belief that constipation increases the risk for colorectal cancer.

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Cortactin is a sensitive biomarker relative to the poor prognosis of human hepatocellular carcinoma

Background: Cortactin is an important regulator involved in invasion and migration of hepatocellular carcinoma (HCC). The aim of this study was to elucidate the forecasting role of cortactin in resectable HCCs. Methods: We compared the invasiveness and motility among liver epithelial cell line and HCC cell lines by using Transwell assay and wound healing assay. We further investigated the CTTN mRNA expression by real-time PCR. Next, 91 HCC and 20 normal liver tissue samples were detected by IHC and real-time PCR. Finally, we analyzed the clinicopathologic features and survival time of the HCC cases. Results: We identified that HepG2, LM3, and SK-Hep-1 had more invasiveness and motility (P <0.05). Compared with liver epithelial cell line, CTTN expression was higher in LM3, HepG2, and MHCC97-L (P <0.01) and lower in SK-Hep-1 (P <0.05). IHC examination showed cortactin expression was closely relative to TNM stage (AJCC/UICC), cancer embolus, and metastasis (P <0.01). Cortactin overexpression indicated a longer survival time of 52 +/- 8.62 months and low expression of a shorter survival time of 20 +/- 4.95 months (P <0.01). Cortactin examination has more predictive power in patients with Child-Pugh grade A and BCLC stage 0-B. Conclusions: Overexpression of cortactin is closely associated with poor human HCCs prognosis that caused by cancer embolus and metastasis. Cortactin and CTTN should be used for differentiating varieties of survival for patients after HCC resection.

via World Journal of Surgical Oncology

Rarely used endoscopic technique ‘fills niche’ in rectal adenoma treatment

Endoscopic transanal resection is effective for the removal of rectal adenomas, say the authors of a 15-year study of the technique.

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Palliative referral rates low despite burden of leukemia

The rate of referrals to palliative or supportive care services for patients with acute leukemia is low, despite this population reporting a high burden of physical and psychological symptoms, show Canadian study results.

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Improved approach to biopsy decisions in prostate cancer

Researchers have developed a strategy for reducing the number of initial biopsies performed among men who are at low risk for prostate cancer.

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Allogeneic HCT feasible in patients with advanced hematologic malignancies

Allogeneic hematopoietic cell transplantation relying on graft-versus-tumor effects is a feasible treatment regimen for patients with advanced hematologic malignancies who cannot tolerate high-intensity regimens, report researchers.

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Orbital lymphoma: diagnostic approach and treatment outcome

Background: Lymphomas of the orbit and orbital adnexae are rare tumors, comprising only 1% of all non-Hodgkin's lymphoma. The majority of non-Hodgkin's lymphomas of the orbit are extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type. Because of nonspecific clinical signs and symptoms, some diagnostic delay may occur. The purpose of the study was to evaluate the diagnostic approach in orbital lymphomas and to analyze their treatment outcome. Methods: In the period from 2006 to 2012, from a group of 135 patients with tumors of the orbit, we identified 11 patients diagnosed with orbital lymphoma. This patient cohort was reviewed retrospectively. Results: The patient group consisted of 11 patients (seven females, male males) with a median age of 57.7 years (range 42 to 88 years). Orbital swelling, pain and motility impairment were the leading clinical symptoms. Diagnosis was confirmed by surgical biopsy. Depending on the anatomic location of the tumor, a surgical biopsy was taken using a blepharoplasty incision, a lateral orbitotomy or a navigation-guided biopsy. The predominant histology was extranodal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue type (82%). All patients underwent complete clinical staging. These were clinical stage IEA in seven patients, and stages IIEA (n = 2) and IIIEA (n = 2) in four patients . Patients in stage IEA were treated with radiation therapy alone, with radiation doses between 25 and 40 Gy, and patients with stage IIEA received systemic chemotherapy with bendamustin/rituximab. Those two patients diagnosed with diffuse large B-cell lymphoma and mantle cell lymphoma received systemic chemotherapy according to the R-CHOP protocol. Conclusions: Owing to unspecific clinical symptoms, some diagnostic delay may occur in orbital lymphoma. If unspecific orbital symptoms are present, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis. Once diagnosis is established and staging is complete, radiation therapy is the recommended treatment for stage IEA patients. Systemic chemotherapy is indicated in selected stage IIEA patients and in patients with stage IIIEA disease.

via World Journal of Surgical Oncology

Radiosurgery gains more focus after brain tumor resection

Postoperative stereotactic radiosurgery is most suitable for the management of brain metastases when gross total resection is possible and lower volumes of radiation exposure is called for.

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Long-term outcome of giant cell tumor of bone involving sacroiliac joint treated with selective arterial embolization and curettage: a case report and literature review

Background: Giant cell tumor of the sacrum, especially involving the sacroiliac joint, is rare, but is particularly challenging to treat. The long term outcome of a patient was studied with giant cell tumor involving the sacroiliac joint treated with selective arterial embolization and curretage.MethodOne patient with giant cell tumor involving the sacroiliac joint was treated with selective arterial embolization and curettage in our hospital in October 2002. The curettage and bone grafting was done after two times of selective arterial embolization;1600 ml of blood were transfused and no complications developed during the operation. Results: At the final follow-up of 9 years after the operation, no local recurrence and metastasis developed and she retained normal activity in daily life. Conclusion: We think it is an optimal treatment for giant cell tumor involving the sacroiliac joint, with repeated selective arterial embolization and curettage, which has the advantage of less injury, less blood loss and fewer complications.

via World Journal of Surgical Oncology

Two-tier urinary screening has positives and negatives in bladder cancer

A two-tiered screening approach comprising dipstick testing for hematuria followed by testing for molecular markers of bladder cancer may significantly reduce the number of men who are referred for cystoscopy compared with dipstick testing alone, show study findings.

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Obesity, diabetes mellitus, and the risk of female breast cancer in Eastern China

Background: This study was designed to explore the relationship between obesity, diabetes mellitus (DM), and female breast cancer in Eastern China. Methods: A 1:3 matched case--control study was carried out, comprising 123 women with breast cancer and 369 controls. All of the 492 subjects were selected from a previous epidemiological survey of 122,058 women in Eastern China. Results: There were significant differences between the case and control groups in waist circumference and body mass index (BMI), but not in waist to hip ratio or hip circumference. There was a significant difference between the two groups in BMI for post-menopausal women, and a significant difference in waist circumference for pre-menopausal women. After adjustment for other factors, BMI was still significantly associated with breast cancer (odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.14 to 2.19). DM was significantly associated with breast cancer (OR = 3.35, 95% CI 1.02 to 11.01) in the univariate analysis but not in the multivariate analysis (P = 0.059). Conclusions: Obesity might be a risk factor for female breast cancer. We found different strengths of association for women with different menopausal status when we examined the relationship between obesity and breast cancer. The association between DM and female breast cancer should be further confirmed with larger sample sizes.

via World Journal of Surgical Oncology

A dynamic clinical pathway for the treatment of patients with early breast cancer is a tool for better cancer care: implementation and prospective analysis between 2002--2010

Background: Due to increasing the complexity of breast cancer treatment it is of paramount importance to develop structured care in order to avoid a chaotic and non-consistent management of patients. Clinical pathways, a result of the adaptation of the documents used in industrial quality management namely the Standard Operating Procedures, can be used to improve efficiency and quality of care. They also aim to re-centre the focus on the patient's overall journey, rather than the contribution of each specialty or caring function independently. Methods: The effect of the implementation and prospective systematic evaluation of a clinical care pathway for the management of patients with early breast cancer in a single breast unit is evaluated over a long time interval (between 2002 and 2010). Annual analysis of predefined clinical outcome measures, service indicators, team indicators, process indicators and financial indicators was performed. Pathway quality control meetings were organized at least once a year. Systematic feedback was given to the team members, and if necessary the pathway was adapted according to evidence based literature data and in house pathway related data in order to improve quality. Results: The annual number of patients included in the pathway (289 vs. 390, P <0.01), proportion of patients with Tis-T1 tumors (42% vs. 58%, P <0.01), negative lymph nodes (44% vs. 58%, P <0.01) and no metastases at diagnosis (91.5% vs. 95.9%) has risen significantly between 2002 and 2010. Evolution of mandatory quality indicators defined by EUSOMA shows a significant improvement of quality of cancer care. Particularly, the proportion of patients having anti-hormonal therapy (84.8% vs. 97.4%, P = 0.002) and adjuvant chemotherapy according to the guidelines (72% vs. 95.6%, P = 0.028) increased dramatically. Patient satisfaction improved significantly (P <0.05). Progression free 4-year survival was significantly higher for all patients, for T1 tumors only and for T2-T4 tumors only, treated between 2006 to 2008 compared to between 1999 to 2002 and 2003 to 2005 (P = 0.006, P = 0.05, P = 0.06, respectively). Overall 4-year survival of the entire population treated between 2006 and 2008 was significantly better (P = 0.05). Conclusions: Although the patient characteristics changed over the years due to better screening, this clinical pathway and regular audit of quality indicators for the treatment of patients with operable breast cancer proved to be important tools to improve the quality of care, patient satisfaction and outcome.

via World Journal of Surgical Oncology

Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia

Background: Activating mutations [internal tandem duplication (ITD)] or overexpression of the FMS-like tyrosine kinase receptor-3 (FLT3) gene are associated with poor outcome in acute myeloid leukemia (AML) patients, underscoring the need for novel therapeutic approaches. The natural product silvestrol has potent antitumor activity in several malignancies, but its therapeutic impact on distinct molecular high-risk AML subsets remains to be fully investigated. We examined here the preclinical activity of silvestrol in FLT3-ITD and FLT3 wild-type (wt) AML. Methods: Silvestrol in vitro anti-leukemic activity was examined by colorimetric cell viability assay, colony-forming and flow cytometry assays assessing growth inhibition and apoptosis, respectively. Pharmacological activity of silvestrol on FLT3 mRNA translation, mRNA and protein expression was determined by RNA-immunoprecipitation, qRT-PCR and immunoblot analyses, respectively. Silvestrol in vivo efficacy was investigated using MV4-11 leukemia-engrafted mice. Results: Silvestrol shows antileukemia activity at nanomolar concentrations both in FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7nM, respectively) and patients' primary blasts [IC50 = ~12nM (FLT3-wt) and ~5nM (FLT3-ITD)]. Silvestrol increased apoptosis (~4fold, P = 0.0001), and inhibited colony-formation (100%, P < 0.0001) in primary blasts. Silvestrol efficiently inhibited FLT3 translation reducing FLT3 protein expression by 80--90% and decreased miR-155 levels (~60%), a frequently co-regulated onco-miR in FLT3-ITD-positive AML. The median survival of silvestrol-treated vs vehicle-treated mice was 63 vs 29 days post-engraftment, respectively (P < 0.0001). Conclusions: Silvestrol exhibits significant in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of FLT3 and miR-155 expression. These encouraging results warrant a rapid translation of silvestrol for clinical testing in AML.

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Hospital volume impacts survival in advanced HNSCC

Higher hospital volume is associated with better survival in patients with advanced head and neck squamous cell carcinoma, an analysis of US data suggests.

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Australian GPs told to shake up colorectal cancer referral system

General practitioners should take a more defined and systematic approach to the management of colorectal cancer, say Australian researchers who found that their involvement in the referral pathway was associated with poorer care.

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Colon angiolipoma with intussusception: a case report and literature review

Angiolipomas are frequently observed benign tumors. They have a typical vascular component and are often located in subcutaneous tissues, and more rarely, in the gastrointestinal tract. We present the case of a 58-year-old man who complained of abdominal discomfort in the left lower quadrant and two to three bloody stools a day without any obvious etiology. These symptom became more severe in the next three days, due to a large angiolipoma located in the descending colon, which was diagnosed intraoperatively. In a literature review, we found only 22 cases of angiolipomas involving the gastrointestinal tract which are reported in the literature from 1960 to 2012 in PubMed; the key words used in the search are gastrointestinal tract angiolipoma, esophagus, stomach, duodenum, intestine, ileocecal junction, colon, rectum angiolipomas. Colon angiolipoma with intussusception, as seen in this case, is rare and may require emergent surgical intervention.

via World Journal of Surgical Oncology

Antiproliferative and apoptotic effects of beta-elemene on human hepatoma HepG2 cells

Background: beta-elemene, a natural sesquiterpene extracted from the essential oils of Curcuma aromatica Salisb, has been shown to be effective against a wide range of tumors. In this study, the antitumor effect of beta-elemene on a human hepatoma cell line, HepG2, and the mechanism involved have been investigated. Methods: MTT assay was used to determine the growth inhibition of hepatoma HepG2 cells in vitro. Apoptosis of HepG2 cells were demonstrated by fluorescence microscope with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Flow cytometry was performed to analyze the cell cycle distribution of HepG2 cells. The mRNA and protein expression of Fas and FasL were measured by RT-PCR and Western blot analysis. Results: MTT results showed that beta-elemene could inhibit the proliferation of HepG2 cells in a time- and dose- dependent manner. Our results showed beta-elemene had positive effect on apoptosis through fluorescence microscope and flow cytometry assay. Furthermore, beta-elemene could induce the cell cycle arrest of the HepG2 cells in the G2/M phase. Fas and FasL expression were obviously increased after beta-elemene treatment in both mRNA and protein level. Conclusion: The present study indicates that beta-elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells, and the apoptosis induction is related with up-regulating of Fas/FasL expression.

via Cancer Cell International

Peripheral T-cell lymphoma presenting as testicular mass; a diagnostic challenge

Background: T-cell lymphomas involve the testis infrequently, which deserve special attention because of the poor prognosis and the need to make an appropriate diagnosis, which could lead to a better therapeutic strategy.Case presentationA 40-year-old man presented with right testicular swelling for past three months. The swelling was painless, hard and rubbery. Testicular ultrasound showed diffuse increase in size of the testicle, with alteration in its echogenicity. The patient underwent orchidectomy, and based on histopathological and immunohistochemical tests, a peripheral T-cell lymphoma, not otherwise specified was diagnosed. Conclusion: Testicular peripheral T-cell lymphomas are rare and aggressive cancers, with clinical differentials of seminoma and non-neoplastic conditions.

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Two-tier urinary screening has positives and negatives in bladder cancer

A two-tiered screening approach comprising dipstick testing for hematuria followed by testing for molecular markers of bladder cancer may significantly reduce the number of men who are referred for cystoscopy compared with dipstick testing alone, show study findings.

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Induction chemotherapy in patients with resectable head and neck squamous cell carcinoma: a meta-analysis

Background: Induction chemotherapy has been investigated as a possible strategy to shrink or downstage locally advanced head and neck cancers, providing opportunity to remove the lesions completely after induction chemotherapy, especially in the patients with resectable advanced disease. The aim of this study was to investigate the definitive effect of induction chemotherapy in patients with resectable head and neck squamous cell carcinoma. Methods: A meta-analysis of randomized trials (1965--2011) was performed on the impact of induction chemotherapy on survival, disease control, and toxicity in this population of patients. Kaplan-Meier curves were read by Engauge-Digitizer. Data combining was performed using RevMan. Results: Fourteen trials (2099 patients) were involved in this analysis. There was no significant difference on overall survival, disease free survival, or locoregional recurrence between the patients treated with and without induction chemotherapy (P >0.05). However, the patients treated with induction chemotherapy had a lower rate of distant metastasis by 8% (95% confidence interval 1%--16%, P = 0.02) than those treated without induction chemotherapy. In patients with laryngeal cancer, comparing to radical surgery, the larynx could be preserved in responders to induction chemotherapy without survival decease (P >0.05). Induction chemotherapy-associated death was 0%--5%. Conclusions: Based on the results above, there is a significant benefit of induction chemotherapy on decreasing distant metastasis in patients with resectable head and neck squamous cell carcinoma. In patients with laryngeal cancer, induction chemotherapy provides larynx preservation in responders to induction chemotherapy.

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Beclin1 inhibition promotes autophagy and decreases gemcitabine-induced apoptosis in Miapaca2 pancreatic cancer cells

Background: Beclin1 is a well-known key regulator of autophagy, which is also a haploinsufficient tumor suppressor. Current studies revealed that down-regulation or monoallelic deletions of Beclin1 were frequently found in various cancers. The purpose of this study was to investigate the effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of pancreatic cancer cells. Methods: Beclin1 expression was inhibited by siRNA transduction and gene expression was determined by Real-time PCR and Western blot. The effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of Miapaca2 cells were analyed through LC3 expression, cell viability, cell cycle and apoptosis by using Western blot Results: We observed that Beclin1 silence promoted microtubule-associated protein 1 light chain 3-II (LC3-II) protein formation and increased punctate fluorescent signals in Miapaca2 cells transfected with green fluorescent protein (GFP)-tagged LC3. Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis of Miapaca2 cells. Conclusion: Our data suggested that Beclin1 silence not only up-adjusted autophagy process, but also played an important role in the regulation of apoptosis. Beclin1 inhibition could inhibit apoptosis signaling induced by Gemcitabine in Miapaca2 cells.

via Cancer Cell International

Arsenic trioxide inhibits the proliferation of myeloma cell line through notch signaling pathway

Arsenic Trioxide (ATO) has shown remarkable efficacy for the treatment of multiple myeloma (MM). However, the mechanism by which ATO exerts its inhibitory effect on the proliferation of myeloma cells remains to be clarified. We study the inhibitory effect of ATO at various concentrations on the proliferation of the myeloma cell line RPMI 8226 and discussed the molecular mechanism of ATO on myeloma cell line. Our results proved that ATO had a significant dose-dependent and time-dependent inhibitory effect on the expressions of the Notch receptor (Notch1) and Notch ligand (Jag2). Data from the real-time PCR assay showed that the mRNA expression levels of the Jag2 gene and its downstream gene Hes1 were both significantly down-regulated after the myeloma cells were treated with ATO while the expression of the tumor suppressor gene PTEN was up-regulated. These results elucidated the molecular mechanism underlying the ATO mediated inhibition of myeloma cell proliferation. This is the first report on the anti-myeloma activity in myeloma cells through inhibition of the Notch signaling pathway.

via Cancer Cell International

Synchronous triple carcinoma of the colon and rectum

Synchronous multiple colorectal cancers are defined as multiple malignant colorectal tumors that occur simultaneously. All tumors are distant from each other, and none are the result of metastasis from other tumors. Here, we present a case of a 79-year-old man who was admitted to our hospital because of a 3-month history of abdominal pain associated with anemia, loss of appetite, and body weight loss. The patient did not have a family history of cancer. Computed tomography revealed bowel wall thickness and mesentery inflammation at the hepatic flexure of the colon and cecum. Colonoscopy revealed a tumor located 10 cm from the anal verge. Colonoscopic examination of the large bowel was not possible because of bowel obstruction due to the rectal tumor. Synchronous triple adenocarcinoma of the colon and rectum was confirmed by pathologic examination. The tumor was surgically resected by two-segment resection of the colon, low anterior resection, and right hemicolectomy. We used intraoperative colonoscopy to confirm that there were no other lesions after the resection of the three tumors. To the best of our knowledge, this is the first case of synchronous triple carcinoma of the colon and rectum in Taiwan. We consider that comprehensive preoperative study, extensive intraoperative exploration, and radical resection can increase the survival rate of patients with synchronous multiple colorectal cancers.

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Effect of preoperative chemotherapy on postoperative liver regeneration following hepatic resection as estimated by liver volume

Background: In order to analyze postoperative liver regeneration following hepatic resection after chemotherapy, we retrospectively investigated the differences in liver regeneration by comparing changes of residual liver volume in three groups: a living liver donor group and two groups of patients with colorectal liver metastases who did and did not undergo preoperative chemotherapy. Methods: This study included 32 patients who had at least segmental anatomical hepatic resection. Residual liver volume, early postoperative liver volume, and late postoperative liver volume were calculated to study the changes over time. From the histopathological analysis of chemotherapy-induced liver disorders, the effect on liver regeneration according to the histopathology of noncancerous liver tissue was also compared between the two colorectal cancer groups using Kleiner's score for steatohepatitis grading {Hepatology, 41(6):1313--1321, 2005} and sinusoidal obstruction syndrome (SOS) grading for sinusoidal obstructions {Ann Oncol, 15(3):460--466, 2004} . Results: Assuming a preoperative liver volume of 100%, mean late postoperative liver volumes in the three groups (the living liver donor group and the colorectal cancer groups with or without chemotherapy) were 91.1%, 80.8%, and 81.3%, respectively, with about the same rate of liver regeneration among the three groups. Histopathological analysis revealed no correlation between either the Kleiner's scores or the SOS grading and liver regeneration. Conclusions: As estimated by liver volume, the level of liver regeneration was the same in normal livers, tumor-bearing livers, and post-chemotherapy tumor-bearing livers. Liver regeneration was not adversely affected by the extent to which steatosis or sinusoidal dilatation was induced in noncancerous tissue by chemotherapy in patients scheduled for surgery.

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Anti-cancer effects of ginsenoside compound k on pediatric acute myeloid leukemia cells

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease and remains clinically challenging. Currently chemotherapies are frequently associated with treatment-related death and long-term side effects. Therefore, alternative approaches with lower toxicity are highly desired. Ginsenosides and metabolites are the main ingredients responsible for the multiple pharmaceutical functions of ginseng, which is one of the most commonly consumed herbal medicines world widely. In the present study, we demonstrated that compound K, a major ginsenoside metabolite, inhibited the growth of the clinically relevant pediatric AML cell lines in a time- and dose-dependent manner. This growth inhibitory effect was attributable to suppression of DNA synthesis during cell proliferation. Furthermore, we observed significant G1 cell cycle arrest and apoptosis induced by compound K. The induction of apoptosis was accompanied by DNA double strand breaks. Our findings suggest that as a low toxic natural reagent, compound K could be a potential drug for pediatric AML intervention and to improve the outcome of pediatric AML treatment.

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Impact of surgical waiting time varies with genitourinary neoplasm type

Prolonged surgical waiting times can have a greater negative impact on outcome in some types of genitourologic neoplasms than others, say researchers.

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Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases

Background: More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. Methods: From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. Results: In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. Conclusions: Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.

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Extranodal Rosai--Dorfman disease: a rare soft tissue neoplasm masquerading as a sarcoma

IntroductionRosai--Dorfman disease (RDD) is a rare proliferative histiocytic disorder of unknown etiology. RDD typically presents with generalized lymphadenopathy and polymorphic histiocytic infiltration of the lymph node sinuses; however, occurrences of extranodal soft tissue RDD may rarely occur when masquerading as a soft tissue sarcoma.Materials and methods: A comprehensive search of all published cases of soft tissue RDD without associated lymphadenopathy was conducted using PubMed and Google Scholar for the years 1988 to 2011. Ophthalmic RDD was excluded. Results: Thirty-six cases of extranodal soft tissue RDD, including the current one, have been reported since 1988. Anatomical distribution varied among patients. Four (11.1%) patients presented with bilateral lesions in the same anatomic region. Pain was the most common symptom in six (16.8%) patients. Sixteen (41.6%) patients were managed surgically, of which one (2.8%) case experienced recurrence of disease. Conclusion: RDD is a rare inflammatory non-neoplastic process that should be considered in the differential diagnosis of a soft tissue tumor. Thus, differentiation of extranodal RDD from more common soft tissue tumors such as soft tissue sarcoma or inflammatory myofibroblastic tumor is often difficult and typically requires definitive surgical excision with histopathological examination. While the optimal treatment for extranodal RDD remains ill-defined and controversial, surgical excision is typically curative.

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Primary tracheobronchial mucoepidermoid carcinoma - a retrospective study of 32 patients

Background: This retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment and prognosis of primary tracheobronchial mucoepidermoid carcinoma (MEC). Methods: Clinical data were retrospectively analyzed from 32 patients with pathologically confirmed primary tracheobronchial MEC between January 1990 and December 2010 at Zhejiang Cancer Hospital. The Kaplan-Meier methods were used to estimate and compare survival rates. Results: There were 19 males and 13 females ranging in age from 7 to 73 years, with a median age of 28 years. Twenty-six of the 32 patients were treated with surgery alone. The other six patients were treated with surgery plus postoperative radiotherapy or chemotherapy. Six patients died during the follow-up time. The overall five-year survival rates were 81.25%, whereas the five-year survival rate of seven patients with high-grade tumors was only 28.6%. Stage I and II patients experienced better survival than Stage III and IV patients (the five-year survival rate was 100% and 43.6% respectively, P<0.001). Conclusions: Primary tracheobronchial MEC is a rare disease. Histologic grading and TNM (tumor-node-metastasis)staging are independent prognostic factors. Surgical resection is the primary treatment.

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Surgical outcomes in patients with small cell lung cancer: comparative analysis of computed tomograpy-detected patients with others

Background: It is shown that low-dose computed tomography (CT) screening is useful for a reduction in lung-cancer-specific mortality in heavy smokers. However, the information about effectiveness according to the histological types of lung cancer has not been adequately investigated especially small cell lung cancer (SCLC). The present study was performed to see the clinical benefit of CT screening in patients with SCLC following thoracotomy. Methods: We retrospectively reviewed the outcome in patients with early stage SCLC who initially underwent thoracotomy. The clinical stages and actuarial survival were estimated according to the three means of detection of SCLC: chest CT, radiographic screen, and symptomatically prompted cases. Results: Sixty-nine patients (men/women, 63/6; mean age, 70 years) with SCLC underwent thoracotomy between 1991 and 2010 including chest CT (n = 13), radiographic screening (n = 39), and symptomatically prompted cases (n = 17). Pathological staging information included stage IA (n = 25), IB (n = 8), IIA (n = 13), IIB (n = 5), IIIA (n = 11), and IIIB (n = 7). Median survival time was 30.0 (95% confidence interval (CI): 22.0 to 57.0) months, with overall survival at 5 years of 34.3% (95% CI, 23.47 to 47.3). Nine patients (69%) with stage I were detected by CT which was significantly higher than those in other detection arms. However, there were no significant differences in the survival between CT and other detection arms. Conclusions: CT examination may be useful for detection in early stage SCLC potentially suitable for surgery, but the contribution to better clinical outcome in patients with SCLC remains unclear.

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An investigation of 125I seed permanent implantation for recurrent carcinoma in the head and neck after surgery and external beam radiotherapy

Background: A preliminary assessment was conducted of the feasibility, efficacy, and morbidity of 125I seed implantation for recurrent head and neck carcinoma after surgery and external beam radiotherapy. Methods: Nineteen patients with recurrent head and neck carcinomas underwent 125I seed implantation under ultrasound or computed tomography guidance. The actuarial D90 of 125I seed implantation ranged from 90 to 160 Gy (median, 131 Gy). The follow-up period ranged from 3 to 44 months (median, 11 months). Results: The median local control was 24 months (95% confidence interval, 10.2 to 37.8). The one- year, two-year and three-year local controls were 73.3%, 27.5% and 27.5%, respectively, whereas the one-year, two-year and three-year survival rates were 53.0%, 18.2% and 18.2%, respectively, and the median survival was 13 months (95% confidence interval, 6.6 to 19.4). A total of 26.3% of patients (5/19) died of local recurrence and 21.1% of patients (4/19) died of metastases. One suffered from a grade 1 skin reaction. Conclusions: I seed implantation is feasible and safe as a salvage treatment for patients with recurrent head and neck cancers. The high local control results and low morbidity merits further investigation.

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Complete resection of recurrent and initially unresectable dermatofibrosarcoma protuberans downsized by Imatinib

Curative surgical treatment of recurrent, locally advanced dermatofibrosarcoma protuberans is often limited owing to a close relation of the tumor with important anatomical structures. Targeted therapy with imatinib, a tyrosine kinase inhibitor, may cause significant reduction of tumor volume, thereby enabling radical surgery. This treatment strategy, therefore, offers a chance of cure for selected patients with advanced dermatofibrosarcoma protuberans. In addition, preoperative treatment with imatinib may decrease possible disfigurement related to radical surgery for large tumors.

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RNAi silencing of c-Myc inhibits cell migration, invasion, and proliferation in HepG2 human hepatocellular carcinoma cell line: c-Myc silencing in hepatocellular carcinoma cell

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Although much is known about both the cellular changes that lead to HCC and the etiological agents responsible for the majority of HCC cases, the molecule pathogenesis of HCC is still not well understood. We aimed to determine the effect of c-Myc gene expression on the proliferative, invasive, and migrative capabilities of hepatocellular carcinoma HepG2 cells. Methods: A plasmid- based polymerase III promoter system was used to deliver and express short interfering RNA targeting c-Myc to reduce its expression in HepG2 cells. Western blot analysis was used to measure the protein level of c-Myc in HepG2 cells. The effects of c-Myc silencing on the invasion, motility, and proliferation of HepG2 cells were assessed using a Transwell chamber cell migration assay system and a growth curve assay, respectively. Results: The data showed that plasmids expressing siRNA against c-Myc significantly decreased its expression in HepG2 cells by up to 85%. Importantly, pSilencer-c-Myc transfected cells showed a significantly reduced potential in migration, invasion, and proliferation. Conclusion: C-Myc plays an important role in the development of hepatocellular carcinoma. The data show that down-regulating the c-Myc protein level in HepG2 cells by RNAi could significantly inhibit migration, invasion and proliferation of HepG2 cells. Thus, c-Myc might be a potential therapeutic target for hepatocellular carcinoma.

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Quantitative assessment of the associations between XRCC1 polymorphisms and bladder cancer risk

Background: The XRCC1 polymorphisms have been implicated in bladder cancer risk, but individually published studies show inconsistent results. The aim of our study was to clarify the effects of XRCC1 variants on bladder cancer risk. Methods: A systematic literature search up to September 13, 2012 was carried out in PubMed, EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios with 95% confidence intervals were used to assess the associations between XRCC1 Arg194Trp and Arg399Gln polymorphisms and bladder cancer risk. Heterogeneity and publication bias were also evaluated. Results: A total of 14 and 18 studies were eligible for meta-analyses of Arg194Trp and Arg399Gln, respectively. Regrouping was adopted in accordance with the most probable appropriate genetic models. No obvious heterogeneity between studies was found. For overall bladder cancer, the pooled odds ratios for Arg194Trp and Arg399Gln were 1.69 (95% confidence interval: 1.25 to 2.28; P = 0.001) and 1.10 (95% confidence interval: 1.03 to 1.19; P = 0.008), respectively. After excluding the studies that were not in Hardy--Weinberg equilibrium, the estimated pooled odds ratio still did not change at all. Conclusions: The meta-analysis results suggest that XRCC1 Arg194Trp and Arg399Gln polymorphisms may be associated with elevated bladder cancer risk.

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Delayed adverse events rare in colonoscopy

Researchers have provided evidence that colonoscopy is a well tolerated and worthwhile procedure for colorectal cancer patients, with regard to late-onset and non-gastrointestinal adverse events.

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Use of advanced RT techniques increases in recent years

While the overall rate of radiotherapy use among patients with metastatic cancer in their last year of life was stable between 2000 and 2007, the use of advanced techniques increased during the period, show US study results.

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Technique breathes new life into gastric cancer diagnosis

A nanomaterial breath test can accurately distinguish gastric cancer from benign stomach disorders, preliminary results show.

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Reduced expression of DACT2 promotes hepatocellular carcinoma progression: involvement of methylation-mediated gene silencing

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of HCC; however, the molecular mechanisms that lead to hepatocarcinogenesis and progression are still not clearly understood. Methods: The expression of DACT2 in specimens from 30 paired HCCs and an additional 61 HCC patients after liver transplantation was evaluated by quantitative RT-PCR and immunohistochemical analysis. We investigated the methylation status of the DACT2 promoter region. We also analyzed the alterations of the cell cycle, migration and invasion after DACT2 knockdown. Results: The expression level of DACT2 was significantly lower in HCC tissues than in non-cancerous tissues. Reduced DACT2 expression was associated with large tumor size. DACT2 transcripts were at low levels in hypermethylated liver cancer cells and were restored by exposure to a demethylating agent. Reduced expression of DACT2 in MHCC97L cells induced G1/S arrest, increased cell proliferation, and promoted cell invasion. Conclusions: Our study suggests that DACT2 is silenced by promoter hypermethylation, and reduced DACT2 can promote liver cancer progression. DACT2 may serve as a novel tumor suppressor gene in HCC.

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Prostate tissue androgen content predicts ADT outcome

Determining the androgen content in prostate tissue could predict patients’ responses to androgen deprivation therapy and the risk for castration-resistant prostate cancer, show study findings.

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Fukushima report sheds light on future health risks

A detailed report carried out by the World Health Organization estimates that the risk to the general public inside and outside Japan from the Fukushima nuclear accident is minimal with no anticipated increases in cancer rates.

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Neuromonitoring predicts functional outcome after rectal cancer surgery

Intraoperative neuromonitoring of the bladder and internal anal sphincter can accurately predict postsurgical urinary and anorectal function, research suggests.

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Hashimoto's Thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer

Background: To confirm whether clinical and biochemical parameters or Hashimoto's thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC). Methods: A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented. Results: Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97--4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201--3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563--5.435), and microcalcification (OR = 14.486, 95% CI = 11.374--18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634). Conclusions: The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.

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Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

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Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

Background: The purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors. Methods: A total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed. Results: Treated cases included 15 patients aged 29 +/-7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 +/-12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 +/-4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence. Conclusions: The procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities.

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Stem cell transplantation could be delayed in acute myeloid leukemia

Stem cell transplantation could be delayed until a relapse occurs, without affecting overall survival, in some patients with acute myeloid leukemia, UK researchers report.

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Anti-metabolic syndrome efforts needed for young ALL survivors

Children with acute lymphoblastic leukemia are at risk for developing the metabolic syndrome during maintenance therapy, suggest study findings.

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Pyomyositis associated with chemotherapy for endometrial cancer: a case report

Pyomyositis is a rare complication of chemotherapy for non-hematological malignancies. A 58-year-old woman with endometrial carcinoma, in whom pyomyositis developed during adjuvant chemotherapy, was presented in this report. After initiating empiric antibiotic therapy for febrile neutrocytopenia, screening CT showed multiple abscesses in the lower limbs. Operative drainage of the abscess was effective.

via World Journal of Surgical Oncology

miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor

Background: Diverse functions of microRNAs (miRNAs), including effects on tumorigenesis, proliferation, and differentiation, have been reported, and several miRNAs have also been demonstrated to play an important role in apoptosis. In this study, we investigated the possible role that miRNAs may play in the development of chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor (EWS). Methods: We screened doxorubicin (Dox)-resistant EWS cells to identify any distinct miRNA sequences that may regulate the chemoresistance of EWS cells. The effects of miRNAs were evaluated using a chemosensitivity assay. The possible target genes of the miRNAs were predicted using a web-based prediction program. Results: We found miR-125b to be upregulated in two different Dox-resistant EWS cell lines. The upregulation of miR-125b was also confirmed in the EWS tumors having survived chemotherapy regimen which includes doxorubicin. When miR-125b was knocked down in EWS cells, both the Dox-resistant and parental cells showed an enhanced sensitivity to doxorubicin, which was associated with the upregulation of the pro-apoptotic molecules, p53 and Bak. Inversely, the overexpression of miR-125b in parental EWS cells resulted in enhanced drug resistance, not only to doxorubicin, but also to etoposide and vincristine. Conclusions: Our findings suggest that miR-125b may play a role in the development of chemoresistance in EWS by suppressing the expression of the apoptotic mediators, such as p53 and Bak.

via Cancer Cell International

Spontaneous rupture of primary splenic angiosarcoma: a case report and literature review

Background: Primary angiosarcoma of the spleen is a rare mesenchymal malignant tumor of vascular origin often with a poor prognosis, due to its high metastatic potential. This disease often presents with atraumatic rupture and lethal hemorrhage.Case presentationWe report a case of a 65-year-old man who presented with abdominal pain, anemia, thrombocytopenia, and palpable abdominal mass with unstable blood pressure. Laparotomy revealed a huge actively bleeding spleen, thus splenectomy was performed. Some liver metastasis foci were also found during the procedure. Histopathology diagnosis of the removed spleen was primary splenic angiosarcoma. The patient was discharged on the 10th day post operation with no complication. Conclusions: Splenic angiosarcoma should be considered one of the differential diagnoses in patients with spleen parenchymal lesions. Definitive diagnosis requires laparotomy followed by splenectomy. In the majority of the patients with spleen angiosarcoma, metastatic diseases have already occurred at the time of laparotomy, so splenectomy is an approach more for diagnostic purpose rather than curative purpose.

via World Journal of Surgical Oncology

FTO function may encompass more than body mass

Three variants in the fat mass and obesity associated gene are associated with significant predisposition to melanoma, show findings published in Nature Genetics.

via Med Wire News

Advanced breast cancer concerns raised for young women

US study findings reveal a worrying increase in the incidence of advanced breast cancer in young women in recent years.

via Med Wire News

Androgen deprivation therapy interferes with diabetes control

Androgen deprivation therapy for prostate cancer hampers glycemic control in men with diabetes, report researchers.

via Med Wire News

Clinicopathological characteristics and prognostic factors in young patients after hepatectomy for hepatocellular carcinoma

Background: The aim of this study was to analyze the clinicopathological characteristics and the prognostic factors for survival and recurrence of young patients who had undergone hepatectomy for hepatocellular carcinoma. Methods: Between 1990 and 2010, 31 patients aged 40 years or younger (younger patient group) among 811 consecutive patients with hepatocellular carcinoma who had undergone primary hepatectomy were analyzed with regard to patient factors, including liver function, tumor factors and operative factors. The clinicopathological characteristics of the younger patients were compared with those of patients over the age of 40 (older patient group). Then the prognostic factors of the younger patients were analyzed. Continuous variables were expressed as the means +/- standard deviation and compared using the chi2 test for categorical variables. Overall survival and recurrence-free survival rates were determined by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis. Results: In the younger patients, the rates of HBs-antigen-positivity, high alpha-fetoprotein, portal invasion, intrahepatic metastasis, large tumors, low indocyanin green retention rate at 15 minutes, and anatomical resection were significantly higher than the same measures in the older patients. The five-year overall survival rate of the young patients was 49.6%. The prognostic factors of survival were HCV-antibody-positivity and low albumin status. Prognostic factors of recurrence were multiple tumors and the presence of portal invasion. Conclusions: In younger patients, survival appeared to be primarily affected by liver function, while recurrence was affected by tumor factors. Young patients with hepatocellular carcinoma should be aggressively treated with hepatectomy due to their good pre-surgical liver function.

via World Journal of Surgical Oncology

Kallikrein gene variants modulate OSCC development

Polymorphisms in the kallikrein7 and kallikrein10 genes are associated with the development and progression of oral squamous cell carcinoma, a study in Taiwanese men indicates.

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Significance of CD133 expression in esophageal squamous cell carcinoma

Background: CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers. Methods: We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR). Results: Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018). Conclusions: This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

via World Journal of Surgical Oncology