Showing papers in "Journal of Solid Tumors in 2012"
TL;DR: Within the limits of this retrospective trial, elderly patients with CRC tend to have more rectal and non-metastatic cancers, and more comorbidities were less likely to receive chemotherapy particularly in the adjuvant setting.
Abstract: Objective: This work was conducted to study colorectal carcinoma (CRC) in Gharbiah district, Egypt and to verify the effect of age on the treatments and their outcomes. Methods: B etween 2000 and 2002, 293 cases with CRC were identified in the Gharbiah population based cancer registry (GPBCR); 159 of whom were treated at Tanta Cancer Center (TCC). Patients were grouped into elderly and non-elderly ( ≥ and < 65 years, respectively). Results: CRC was the 6th cancer in Egypt, representing 4% of the total cancers and 53% of GIT cancers. The median age was 53 years with male predominance. Colon cancers were more common than rectal cancers. Most patients had tumors that were localized, low grade and adenocarcinoma (AC). Constipation, abdominal pains and bleeding per rectum were the commonest complaints. Surgery, radiotherapy and chemotherapy were adopted in 84, 28 and 72% of patients, respectively. The median OS and PFS were 23 and 25 months (95%CI: 17-29 and 11.8-18.2), respectively. Compared to non-elderly, elderly patients were more likely to have rectal tumors, non-AC histology, non-metastatic disease; more comorbidities were less likely to receive chemotherapy particularly in the adjuvant setting ( P < 0.05 for all). The OS and PFS of elderly patients were not statistically different from the non-elderly. Conclusions: Within the limits of this retrospective trial, elderly patients with CRC tend to have more rectal and non-metastatic cancers. They were more likely to have comorbidities and less likely to receive chemotherapy. However, the OS and DFS were comparable to non-elderly.
21 citations
TL;DR: It is shown that Pluronic® block copolymers can encapsulate SiQDs to make them water dispersible and suitable for cancer imaging applications, and show promise for targeted diagnostic applications without possessing elementally toxic components.
Abstract: Objectives: Silicon quantum dots (SiQDs) are of great interest for bio - imaging applications due to their tunable luminescence, low toxicity, unique surface chemistry, and high quantum yield. Most synthesis routes produce SiQDs that are not water-dispersible, making them unattractive for biological applications. Here, we show that Pluronic® block copolymers can encapsulate SiQDs to make them water dispersible and suitable for cancer imaging applications. Methods: Transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, and temperature and pH stability measurements were used to evaluate these Pluronic®-encapsulated SiQDs (PSiQDs). The particles were also tested targeted in vitro imaging and in vivo bio - distribution. Results: Encapsulation with Pluronic® polymers renders the SiQDs water dispersible, preserves their optical properties, protects them from oxidation, and prevents aggregation. Surface modification of the PSiQDs with pancreatic cancer targeting moieties, anti-claudin-4 and anti-mesothelin, led to enhanced uptake of these nanoconstructs in comparison to PSiQDs modified with folate as the targeting moeity. Conclusions: The particles are stable at biological conditions, and show promise for targeted diagnostic applications without possessing elementally toxic components.
18 citations
TL;DR: Research studies are still ongoing to identify and establish new biochemical parameters/markers that can be of used not only in advanced disease, but also in early stages of the diagnostic workup of breast cancer.
Abstract: Breast cancer is one of the most common cancer in women, presented with a lump and skin colour change, is one of thecommonest cancer in women. A wide variety of tumor markers viz. uPA, BRCA1 & 2, Ki76, ER, PR, HER etc. are usedfor establishing carcinoma of breast but none being a proper diagnostic tool for early detection, though each one has itsown prognostic value. Though proposed but only few are used in clinical practice, research studies are still ongoing toidentify and establish new biochemical parameters/markers that can be of used not only in advanced disease, but also inearly stages of the diagnostic workup of breast cancer.
10 citations
TL;DR: This dose-dilution combinatorial strategy fulfills the need for increased tumor sensitivity and efficacy and reduces drug resistance and toxicity associated with dose dense strategy of temozolomide treatment in this melanoma model.
Abstract: Background: Carboxyamidotriazole orotate (CTO) is the orotic acid salt of 5-amino-1(4-(4-chlorobenzoyl)-3, 5-dichlorobenzyl)-1, 2, 3-triazole-4-carboxamide (CAI). CTO possesses increased solubility as compared to CAI as the free base. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor-operated, calcium-channel-mediated calcium influx. CTO can inhibit calcium-sensitive signal transduction in the VEGF and the PI3K pathways, inhibition of FGF-2-induced tyrosine kinase, VEGF-mediated activation of phospholipase Cy, generation of IP3 and nitric oxide synthase activation, and induction of apoptosis in imatinib mesylate resistant CML cells by downregulating bcr-abl. Methods: Different combinations of CTO and temozolomide were first tested in female athymic NCr- nu/nu mice to evaluate tolerance of the combination. The tolerated combinations were then tested to evaluate the antitumor activity against subcutaneously implanted human LOX IMVI melanoma xenografts. Results: Oral CTO at doses of 513 or 342 mg/kg/dose Q1D × 14 resulted in inhibition of tumor growth ( p <0.001 and p =0.004). Oral TEM at doses of 90 and 60 mg/kg/dose Q4D × 3 resulted in dose-dependent inhibition of tumor growth ( p <0.001 and p <0.001). Oral CTO at 513 or 342 mg/kg/dose in combination with temozolomide 90 mg/kg/dose resulted in comparable tumor inhibition to temozolomide alone. However, oral CTO at 513 mg/kg/dose in combination with temozolomide 60mg/kg/dose resulted in additive antitumor activity compared to each drug alone. Also, CTO at 342 mg/kg/dose in combination with temozolomide 60mg/kg/dose had more than additive antitumor activity and was statistically different from the group treated with temozolomide 60 mg/kg/dose alone ( p =0.001). Conclusions: These results suggest that this combination of previously configured therapeutic doses of temozolomide with CTO enhances the sensitivity of temozolomide and may permit use of lower temozolomide doses to obtain an optimum antitumor effect in combination therapy. This dose-dilution combinatorial strategy fulfills the need for increased tumor sensitivity and efficacy. Additionally, this strategy reduces drug resistance and toxicity associated with dose dense strategy of temozolomide treatment in this melanoma model.
10 citations
TL;DR: Males with the lower digit ratio seem to be more prone to undergo malignization of prostatic lesions, inferring that digit ratio could add to the research of etiological factors and be a putative marker for the screening of patients’, especially in a admixed population.
Abstract: Objective: Digit ratios are considered putative markers for prenatal hormone exposure, as well as the action of HOX andAR genes. Such genes have been connected to carcinogenesis and digit ratio could help to identify patients that bear suchpredisposition. The purpose of this study was to investigate the possible correlations between digit ratio, prostate cancer(PCA) - the most common cancer in men – and benign prostate hyperplasia (BPH) in a multiethnic sample of men between50 and 80 years, the main risk group for this disease.Methods: Digital images of the right hands of patients diagnosed with PCA (n=40), BPH (n=40) and age-matchedcontrols (n=40) were obtained. Fingers were measured using Adobe Photoshop 7.0® and the mean ratios between the 2ndand 4th digits were compared. Data were analyzed by Student’s t test and regression models (α=0.05). Risk factors (dietaryfactors, tobacco consumption, age and familial history) were similar among the three study groups.Results: Males in the PCA group presented significantly lower digit ratio (P=0.04) in comparison with males withoutprostatic lesions.Conclusions: Males with the lower digit ratio seem to be more prone to undergo malignization of prostatic lesions. Similarrisk factors for the three groups allows us to infer that digit ratio could add to the research of etiological factors and be aputative marker for the screening of patients’, especially in a admixed population.
10 citations
TL;DR: It is proposed that, by supplying external electromagnetic (light) energy within parameters capable of powering and regulating electrochemical biological systems, photobiomodulation may help restore homeostasis/homeokinesis–inducing physiologically reparative effects for disease reversal in cancer and other complex diseases.
Abstract: It has been argued that loss of homeostasis is what, in essence, allows cancer cells to divide and invade tissues. Hence, novel anticancer therapies should aim not only at killing cancer cells, but at reestablishing homeostasis /homeokinesis. This review aims to present and discuss evidence on the potential use of laser photobiomodulation in the treatment of solid tumors. We propose that, by supplying external electromagnetic (light) energy within parameters capable of powering and regulating electrochemical biological systems, photobiomodulation may help restore homeostasis/homeokinesis–inducing physiologically reparative effects for disease reversal in cancer and other complex diseases. This view is based on more than two decades of research, which indicates that light can modulate physiologic energy pathways and, in particular, ATP generation and signaling via the “classic” respiratory chain pathway and through light-water interactions in tissues and oxygen-independent mechanisms.
10 citations
TL;DR: Evidence is provided that RNAi may be used for the treatment of cervical cancer by intra-tumor injection by injecting lentiviral shRNA into the tumor of xenografted cervical cancer HeLa cells.
Abstract: Objectives: HPV is known to play a key role in the growth and maintenance of cervical cancer. Its early genes E6 and E7 can activate several intracellular signal pathways for carcinogenesis. Studies have shown that in vitro knockdown of E6 and E7 can reduce the survival ability of cervical cancer cell lines. In this study, we tested the effect of a lentiviral shRNA against E6/E7 on the tumor growth of xenografted cervical cancer HeLa cells. Methods: In vitro , the growth of HeLa cells transduced with lentiviral shRNA against E6/E7 was compared to controls. In vivo , the RAG -/- mice, which are deficient in T and B lymphocytes were used to establish the HeLa xenografted model. In the treatment group, shRNA against E6/E7 was injected into the tumor directly 30 days after HeLa cell injection when tumors have formed and the injection was repeated at day 60. A lentiviral vector without shRNA was injected in the control group . Results: HeLa cells transduced with lentiviral shRNA against E6/E7 grew slower than those with transduced with the control vector. The difference in growth rate was significant at day 4. We also observed that lentiviral shRNA significantly reduced the size of xenografted tumors compared with controls. The average tumor weight is 60% of the controls. Conclusions: Our results provide evidence that RNAi may be used for the treatment of cervical cancer by intra-tumor injection.
9 citations
TL;DR: A case cervical lymph node metastasis in patient with muscle invasive bladder cancer is reported, with poor prognosis and low survival rate.
Abstract: The bladder cancer usually metastasizes to regional pelvic lymph nodes, lungs, liver and bones. Metastasis to non-regional lymph nodes especially cervical lymph nodes is extremely rare presentation. Metastasis to head and neck region is associated with poor prognosis and low survival rate. Here-in we report a case cervical lymph node metastasis in patient with muscle invasive bladder cancer.
8 citations
TL;DR: The ability of heat shock proteins to chaperone peptides; interact with antigen presenting cells through a receptor; stimulate APCs to secrete inflammatory cytokines; and mediate maturation of dendritic cells, permit the utilization of these proteins to develop a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases.
Abstract: Successful vaccine development requires knowing which adjuvants to use and how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. There is growing literature on immuno-regulatory and adjuvant functions of heat shock proteins (HSPs) in the development of preventive and therapeutic vaccines against cancer and infectious diseases. These extremely conserved molecules associate with antigenic peptides from tumor, virus and intracellular bacteria, present these loaded antigens to both MHC class I and class II molecules and activate specific T cells. This review aims to summarize the data on the HSP roles as the efficient tools in cancer. The ability of heat shock proteins to chaperone peptides (e.g., antigenic peptides); interact with antigen presenting cells (APCs) through a receptor; stimulate APCs to secrete inflammatory cytokines; and mediate maturation of dendritic cells, permit the utilization of these proteins to develop a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases. Furthermore, some cancers demonstrate elevated levels of HSPs and their expression has been associated with cell proliferation and disease prognosis. New adjuvant development is needed to identify novel combinations of adjuvants and formulations capable of inducing strong, long lasting humoral and cellular immune responses in humans. Numerous challenges remain related to adjuvant development. Among efficient adjuvants, it has been shown that heat shock proteins induce cross-presentation of antigens by dendritic cells (DC) as well as DC maturation. These properties make HSP-antigen complexes good candidates to prime CD8+ T cell responses against tumor-associated antigens. Moreover, these conserved proteins can be used as diagnostic biomarkers in various cancers.
8 citations
TL;DR: There is a coordinated growth of melanoma cells around neovascular channels, the cell cycle of malignant melanocytes being orchestrated by the three pituitary hormones, PRL, HGH & ACTH, while ACTH & pigment indicate differentiated function.
Abstract: Background: Vicarious production of pituitary hormones by malignant tumors is a well known phenomenon. Prolactin [PRL], human growth hormone [HGH], adenocorticotropic hormone [ACTH] and alpha-melanocyte stimulating hormone [α-MSH] expression has been reported in malignant melanoma tumor cell lines. The present study examines the pattern of expression of the hormones ACTH, PRL and HGH in melanoma with regard to tumor growth and differentiation in relation to angiogenesis. Methods: During angiogenesis the tumor cells encircle a central vessel in layers to form a tumor-vascular-complex [TVC] with a central vessel and a mantle of 5 to 6 layers. Hormone expression is assessed by immunopositivity for PRL, HGH, & ACTH in the tumor-vascular complexes, on serial frozen and paraffin sections and subjected to statistical analysis [t-test or Mann-Whitney U- test]. Results: As two layers accrue the tumor cells acquire PRL & HGH positivity and are associated with a wave of mitotic activity in these layers. Further addition of layers shows ACTH positivity in the outer layers in association with pigmentation. Discussion: There is a coordinated growth of melanoma cells around neovascular channels, the cell cycle of malignant melanocytes being orchestrated by the three pituitary hormones, PRL, HGH & ACTH. The expression of PRL & HGH is related to mitotic activity while ACTH & pigment indicate differentiated function.
7 citations
TL;DR: Cisplatin is the prototype of the chemotherapy class of platinum drugs that include carboplatin and oxaliplatin, which cause cell death by binding to DNA to form DNA adducts, preventing further replication.
Abstract: Cisplatin, like many anti antineoplastic agents, has a rich and interesting history. It was first discovered in 1845 by Dr.Michele Peyrone and given the full chemical name cis-diamminedichloroplatinum (II), also called cis-DDP, though at thetime of its discovery was called ‘Peyrone’s salt’ [1]. The discovery [2] of its cellular toxic effects was not until more than acentury later in experiments with bacteria using platinum electrodes to study the effects of bacterial growth in an electricalfield. Growth was noted to be stunted, with bacteria left alive, but not replicating. After two years, cisplatin was discoveredto be similar to the compounds used in the electrodes and capable of stopping cell growth. This gave rise to experiments inanimals testing the antineoplastic properties of cisplatin and eventually to human trials. Phase I trials began in 1971 and thedrug was FDA approved for use in 1978 [3]. Cisplatin is the prototype of the chemotherapy class of platinum drugs thatinclude carboplatin and oxaliplatin. They cause cell death by binding to DNA to form DNA adducts, preventing furtherreplication [4].
TL;DR: A case of 35 years old male who underwent radical nephrectomy for localized RCC six years back, now presented with mass in the base of tongue which was suspected as carcinoma of tongue and subsequently was confirmed as metastatic RCC following excisional biopsy and was treated with intra-oral electron radiation therapy.
Abstract: Renal cell carcinoma (RCC) has unpredictable and diverse behavior. The classic triad of hematuria, loin pain and abdominal mass is uncommon. About 25 - 30% of patients are found to have metastases at the time of diagnosis. Bones, lungs, liver and brain are the frequent sites of metastases. RCC with metastasis to the oral cavity is rarest manifestation. We report a case of 35 years old male who underwent radical nephrectomy for localized RCC six years back, now presented with mass in the base of tongue which was suspected as carcinoma of tongue; subsequently was confirmed as metastatic RCC following excisional biopsy and was treated with intra-oral electron radiation therapy.
TL;DR: Patients with benign metastatic struma ovarii (also known as Highly differentiated follicular carcinoma of ovarian origin - HDFCO) may affectively be treated with local resection of the extraovarian tumor and subsequent thyroidectomy followed by radioactive iodine ablation.
Abstract: Background: Malignant transformation of thyroid tissue in struma ovarii and metastasis are uncommon. Benign thyroid tissue may spread to the peritoneal cavity in rare cases, and pathologic examination of the peritoneal implants shows multiple nodules of varying sizes of mature thyroid tissue similar to struma ovarii. This condition is termed “peritoneal strumosis”. It is very rare and therefore, both the criteria for diagnosis and its management are under discussion. The recommended treatment of metastatic struma ovarii should contain, in addition to local resection of the extraovarian tumor, total thyroidectomy in conjunction with radioiodine scanning and radioiodine ablation. Case report: A 38 year-old woman had presented with benign struma ovarii 12 years previously. She was referred to our department because of a right ovarian tumor. After confirming the diagnoses of metastatic recurrent benign struma ovarii, we performed debulking surgery with the aim of resecting all tumor masses. The uterus, left adnexa, and pelvic peritoneum were surgically extracted “en bloc”. No macroscopic tumor was left post-operatively. The first post operative 123 I scintography with15 MBq iodine-123 one month post-operatively showed a small but suspicious focus in the front left perivesical pelvic area. In the ventral visual presentation multiple discrete foci, located in right perivesical, supravesical and in the ventral upper abdomen, were seen. We then referred the patient for thyroidectomy and radioiodine ablation. The following periodic follow-ups of the patient did not show any signs of recurrence or progression of the disease. Conclusion: Patient with benign metastatic struma ovarii (also known as Highly differentiated follicular carcinoma of ovarian origin - HDFCO) may affectively be treated with local resection of the extraovarian tumor and subsequent thyroidectomy followed by radioactive iodine ablation.
TL;DR: In medically inoperable patients, a diagnosis of lung cancer can be provisionally made radiographically without pathologic confirmation and local control can be achieved with minimal toxicity with the use of SBRT.
Abstract: Objective: Medically inoperable patients with primary or recurrent lung cancer are increasingly being diagnosed clinically without pathologic confirmation especially for patients with comorbidities that preclude biopsy. The objective of this study is to report the outcomes of medically inoperable patients with unbiopsied primary or recurrent lung carcinoma with SBRT. Methods: From 2008-2011, 22 patients with non-pathologically diagnosed primary or recurrent lung cancer were treated with SBRT. All patients had diagnostic imaging clinically consistent with primary or recurrent lung malignancy. Fifteen patients had primary lung cancer and 7 had recurrent disease previously treated with surgery or fractionated radiotherapy. Median SBRT dose was 50 Gy (Range 40-55 Gy) in a median of 5 fractions (Range 4-10 fractions). Median BED was 100 Gy (Range 72-151.2 Gy). Results: Median follow up is 15.3 months (Range 6.6-33.0 months). Primary tumors had a median longest dimension on the original CT of 1.6cm, which enlarged to 2.0cm ( P <0.001) on serial CT and decreased to 1.3cm ( P =0.003) after SBRT. Recurrent tumors had a median longest dimension of 1.6cm, which increased to 2.7cm ( P =0.33) on repeat CT and subsequently stabilized at 2.7cm after SBRT. On FDG-PET scan, median standard uptake value (SUV) for the entire population is 5.4 before SBRT which decreased to 2.3 ( P <0.001) after treatment. For the entire population, absolute local control was 90.9%. Kaplan-Meier curves estimates at 2 years show regional control 100%, distant control 75%, cancer specific survival 92%, and overall survival 75%. There were no grade 3/4 acute or chronic treatment-related toxicities. Conclusions: In medically inoperable patients, a diagnosis of lung cancer can be provisionally made radiographically without pathologic confirmation. Local control can be achieved with minimal toxicity with the use of SBRT.
TL;DR: Pineal region tumors in children are rare and germinomas, nongerminomatous germ cell tumors and pineoblastoma are the most common.
Abstract: Pineal region tumors in children are rare. A wide diversity of lesion arises from the pineal gland or the surrounding tissues. Among them, germinomas, nongerminomatous germ cell tumors and pineoblastoma are the most common. These tumor do not have pathognomonic imaging findings. However, tumor markers evaluation may narrow the differential diagnosis. Symptoms are usually related to tumor size and location. Treatment depends on tumor type but still the standard management remains unclear.
TL;DR: This editorial presents a view which is very different from commercial-marketing a product or laisoning with producer companies etc, all about developments in cancer research which leads one to understand - what is personalized medicine.
Abstract: Keeping in view the need for corporate communications in cancer research perspective, which means communications serves as the liaison between an organization and public. This editorial presents a view which is very different from commercial-marketing a product or laisoning with producer companies etc. It is all about developments in cancer research which leads one to understand - what is personalized medicine. As the scientific and medical communities begin to decipher the secrets locked in the human genome code, the way we approach the diagnosis, treatment and prevention of disease will change dramatically. With the detection of human genome, scientists have already created large databases filled with thousands of single nucleotide sequence changes. Some of these single nucleotide polymorphisms (SNPs) could define the genetic basis of what keeps healthy or makes us sick. Currently the most common applications for SNP related research tools are gene-disease association studies, drug-gene interactions and drug target validation. Other popular applications are disease susceptibility studies or diagnostics, pharmacogenomic studies for clinical trials, drug target screening, and new technology development.
TL;DR: These long-term data suggest that lumpectomy followed by brachytherapy is feasible and may be an acceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy.
Abstract: Objective: To evaluate our mature follow-up data in women who have developed IBTR following conservation surgeryand post-operative external radiotherapy retreated by lumpectomy followed by interstitial brachytherapy in lieu of salvagemastectomy.Methods: Between 1/1998 and 10/2006, twenty-two patients with TIS or T1 IBTR were offered interstitial low-dose ratebrachytherapy following tumor re-excision as an alternative to salvage mastectomy. All patients had failed lumpectomyfollowed by standard postoperative external beam radiotherapy (range 5000-6480cGy). The recurrent tumors were excisedwith final margins of resection free of residual disease. Tumor bed implantation was then carried out with an interstitialtechnique utilizing 192Iridium with the target volume consisting of the tumor bed plus a minimum 1.0 centimeter margin(minimum standard dose 4500cGy).Results: With a mean follow up of 67.5 months (range 17-115 months) Twenty-one of 22 patients maintained localcontrol at the time of last follow-up or at the time of their death. The single patient who developed a second localrecurrence was treated successfully with mastectomy. Three patients succumbed to systemic disease. Two patientsdeveloped localized skin breakdown. One patient developed a contralateral breast cancer. Long-term cosmetic results asdefined by the Harvard cosmesis scale and the Allegheny General modification were acceptable.Conclusions: These long-term data suggest that lumpectomy followed by brachytherapy is feasible and may be anacceptable alternative to salvage mastectomy in patients who locally fail conservation breast therapy. The upcomingRTOG retreatment trial (RTOG 1014) should help define the role of repeat conservation therapy in IBTR.
TL;DR: Considering interobserver variability, “double reading” is necessary for practical GTV assessment and may facilitate the standardization of treatments, not only of RT but also of surgery and chemotherapy.
Abstract: Background/Objective: The precise definition of the gross tumor volume (GTV) that takes into account intra- and interobserver variability is necessary for high-precision radiotherapy (RT) techniques. The purpose of this study was to demonstrate the practical GTV assessment by a “double reading” approach. Methods: Pretreatment magnetic resonance (MR) imaging, including the post-contrast 3D magnetization-prepared rapid-gradient echo (MP-RAGE) sequence (section thickness 1.0 mm) was performed on a 3T superconducting imager in 50 patients with glioblastoma. MR images were transferred to a RT planning system (RTPS) that provides many opportunities for GTV contouring, e.g., at diagnosis, surgical navigation, and RT deliberations. Independent 2 observers preliminarily contoured the GTV on MR images. After planning-CT scanning, CT images with a 1.0 mm slice interval were transferred to the RTPS, registered with the diagnostic images, and then the preliminarily-contoured strictures were copied onto the CT images and used for GTV assessment. The practical GTV on the planning CT was determined by integrating the interpretations and adding information on postoperative changes. The interobserver variability in GTV contouring was assessed by Bland-Altman analysis and the concordance index. Results: There was substantial interobserver variability in GTV contouring (95% limits of agreement: -29.4%, 16.8%). The mean interobserver concordance rate for the GTV was 82.1% (range 56.5-91.2%). The practical GTVs were significantly larger than the preliminarily-contoured GTVs by both observers ( p < 0.01). Conclusions: Considering interobserver variability, “double reading” is necessary for practical GTV assessment. This approach for volume assessment may facilitate the standardization of treatments, not only of RT but also of surgery and chemotherapy.
TL;DR: A case of 40 years old male who underwent radical nephectomy for localized RCC seven years back, now presented with swelling in neck which was suspected as thyroid malignancy and subsequently was confirmed as metastatic RCC following excisional biopsy and was treated with surgical resection.
Abstract: Renal cell carcinoma (RCC) has unpredictable and diverse behavior. The classic triad of hematuria, loin pain and abdominal mass is uncommon. About, 25 %- 30% of patients are found to have metastases at the time of diagnosis. Bones, lungs, liver and brain are the frequent sites of metastases. RCC with metastasis to the thyroid gland is rarest manifestation. We report a case of 40 years old male who underwent radical nephectomy for localized RCC seven years back, now presented with swelling in neck which was suspected as thyroid malignancy; subsequently was confirmed as metastatic RCC following excisional biopsy and was treated with surgical resection.
TL;DR: Gynecologists are advised to consider the possibility of an appendiceal neoplasm, especially when a dumbbell structure in the lower right abdomen is found on ultrasound, and to recommend a laparotomic approach if the operation is continued.
Abstract: Background: This review focuses on appendiceal mucoceles that have been reported to incidentally mimic ovarian cysts and put the patient at risk of misdiagnosis and, thus, inadequate treatment. Methodology: Review of the literature. Principal findings: Benign mucoceles are the most common form of appendiceal mucoceles and represent about 63-84%, whereas a malignancy is found in 11-20%. Patient presentation is extremely variable for all forms, with, first and foremost, nonspecific symptoms, and patients may also be completely asymptomatic. Thus, the majority of appendiceal mucoceles are discovered incidentally. Women with ovarian cysts also frequently report abdominal pain or nonspecific gastrointestinal symptoms, with about 10% of patients being asymptomatic. Gynecologists perform transvaginal ultrasound as a standard procedure to evaluate pelvic tumors from the uterus, tubes, or ovaries. The ultrasound appearance of appendiceal mucoceles can vary widely from well-encapsulated purely cystic lesions with anechoic fluid, hypoechoic masses with fine internal echoes, or complex hyperechoic masses. Thus, they can mimic ovarian cysts. However, a specific ultrasonographic marker is the so-called “onion skin sign” and its “dumbbell structure”. Even when an appendiceal mucocele is detected during gynecologic surgery, the appropriate surgical treatment would be an open approach, ideally combined with an intraoperative frozen section examination. The gynecologist might choose not to continue with the operation, instead performing the excision of the appendiceal mucocele as a two-step procedure. Conclusion/Significance: We advise gynecologists to consider the possibility of an appendiceal neoplasm, especially when a dumbbell structure in the lower right abdomen is found on ultrasound. If an appendiceal mucocele is incidentally diagnosed during surgery, a laparotomic approach is recommended if the operation is continued. This should be performed by a general surgeon.
TL;DR: This article reviews the RNA-Seq technologies followed by a detailed discussion of current statistical methods for normalization and differential expression analysis.
Abstract: RNA-Seq is a recently developed technology for transcriptome profiling. Numerous advantages of RNA-Seq suggest that it will be the platform of choice for genome-wide expression studies. RNA-Seq generates large volumes of data which require statistical methods for data processing and accurate inference. This article reviews the RNA-Seq technologies followed by a detailed discussion of current statistical methods for normalization and differential expression analysis.
TL;DR: Hypoxia status of micro - metastases is discussed, and related this to cellular proliferation and glucose metabolism, and proposed hypoxia as a therapeutic target for micro- metastases.
Abstract: Most cancer-related deaths are due to the development of metastatic disease rather than the growth of primary tumors. Adjuvant treatment often does not translate into substantial improvements in overall survival; subclinical micro - metastases may be resistant to multiple therapies. Understanding microenvironment factors such as hypoxia, proliferation and glucose metabolism in micro - metastases is of importance for micro - metastases treatment; hypoxia, commonly observed in most primary solid malignancies, is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis and hypoxic tumor cells are more resistant to radiotherapy and some forms of chemotherapy. In this article, we discussed hypoxia status of micro - metastases, and related this to cellular proliferation and glucose metabolism. We also proposed hypoxia as a therapeutic target for micro - metastases.
TL;DR: A 42-year-old Hispanic woman with invasive ductal carcinoma, positive for estrogen and progesterone receptors and negative for HER2, is reported on, a recently approved non-taxane microtubule dynamics inhibitor whose mechanism of action differs from that of other tubulin-targeting agents.
Abstract: Treatment of heavily pretreated patients with metastatic breast cancer is challenging due to the combination of progressive disease and limited treatment options. Because breast cancer in this setting is not curable, treatment goals include improving/maintaining quality of life, reducing tumor-related symptoms, and prolonging survival. We report on a 42-year-old Hispanic woman with invasive ductal carcinoma (T4 N1 M1), positive for estrogen and progesterone receptors and negative for HER2. She had been heavily pretreated with radiation (to bone metastases), hormonal therapy, and multiple systemic therapies—including a nanoparticle albumin-bound paclitaxel/bevacizumab/gemcitabine combination and pegylated liposomal doxorubicin. Because of toxicity or disease progression, none of these treatments was used for more than 4 months. After receiving eribulin (in a clinical trial), the patient remained in stable disease for 21 months and generally tolerated eribulin well. (Thrombocytopenia with resulting gastrointestinal bleeding occurred but was resolved with a dose reduction.) The case is discussed in the context of current treatment goals and modalities in the setting of late-line metastatic breast cancer. Treatment options include newer chemotherapeutic agents such as eribulin, a recently approved non-taxane microtubule dynamics inhibitor whose mechanism of action differs from that of other tubulin-targeting agents.
TL;DR: The case of a 68 year-old woman who presented with weight gain and local compressive symptoms from a known pelvic cystic teratoma was found to contain a well-differentiated malignant carcinoid at the time of surgical excision.
Abstract: Carcinoids are rare neuroendocrine tumors encountered most commonly in the gastrointestinal tract and bronchopulmonary tree. While carcinoids are perhaps best distinguished by their ability to cause the carcinoid syndrome through secretion of vasoactive peptides and amines, the vast majority are asymptomatic. We herein describe the case of a 68 year-old woman who presented with weight gain and local compressive symptoms from a known pelvic cystic teratoma, which was found to contain a well-differentiated malignant carcinoid at the time of surgical excision.
TL;DR: Treatment of stage III NSCLC patients with single-agent vinorelbine CCRT had a better median survival time and 2-year survival rates with fewer toxicities when compared with other therapies.
Abstract: Background: Lung cancer is the most common cancer in the world, and causes 1.3 million deaths annually. Approximately 45% of patients diagnosed with non-small cell lung cancer (NSCLC) have locally advanced stage III disease. Standard treatment is concurrent chemoradiotherapy (CCRT) with two drugs, but severe toxicities are common. Several single-agent CCRTs have been developed to overcome this problem. Methods: We reviewed the records of 24 patients with stage III NSCLC who received single-agent vinorelbine CCRT at the National Cheng Kung University Hospital from January 1, 2005 to May 31, 2009. Nine patients received with vinorelbine intravenous infusion (15 mg/m 2 /week) and fifteen with oral vinorelbine 40mg/m 2 /week. Thoracic radiation was given over 6 weeks in 1.8 Gy/day fractions (total median dose of 59.7 Gy). The primary endpoint was the evaluation of time to progression (TTP) of these patients. The secondary endpoints were analysis of therapy-related toxicities and overall response rate. Results: Median age was 70 years (range: 58-81 years), and median follow-up time was 430 days (range: 101-1363 days). Eighteen patients were male, six were female and the median ECOG grade was 1. Vinorelbine was given for a median of 5.5 weeks (range: 4-8 weeks). All patients completed all planned cycles of CCRT. Seven patients (29.2%) had radiation pneumonitis. No patient had a complete response, and thirteen patients (54.2%) had a partial response. The median time to progression (TTP) was 6.4 months (95% confidence interval: 4-8.7 months), the median survival time was 24 months (95% CI: 13.8-34.9 months), and the 1- and 2-year survival rates were 68.5% and 41.1%, respectively. Conclusion: Treatment of stage III NSCLC patients with single-agent vinorelbine CCRT had a better median survival time and 2-year survival rates with fewer toxicities when compared with other therapies. Oral vinorelbine with its convenience in administration is an ideal choice for CCRT.
TL;DR: The oral mucosal cells are susceptible to genomic instability when exposed to chemotherapy regimens containing alkylating agents which allows a new approach to chemotherapy Regimens and their implications and proposes a new biological matrix for assessing such adverse effects.
Abstract: Objectives: The study of the involvement of non-neoplastic cells with genomic instability has not been sufficiently investigated. Genomic instability induced by treatment chemotherapy with alkylating agents’ employment has been reported in different biological matrices like PBMN, and fpDNA fuDNA. We investigated the possible use of DNA from oral mucosal cells to observe the presence of genomic instability being a simple protocol, applicable and non - invasive. Methods: Genomic instability was determined in oral mucosal cells of 31 women diagnosed with breast cancer before and after chemotherapy with alkylating agents’ presence. MSI was assessed by a panel with five different microsatellite regions. Results: We observed that 77.41% of patients had any genetic alteration in the oral mucosal cells, with a higher number of MSI events by 32.58% compared to LOH events by 24.97%, mainly in the FMR2 (16.29 %) and BAT 26 (13.04%). The control group did not show genomic instability in oral mucosal cells. Conclusions: The oral mucosal cells are susceptible to genomic instability when exposed to chemotherapy regimens containing alkylating agents which allows us a new approach to chemotherapy regimens and their implications and propose a new biological matrix for assessing such adverse effects.
TL;DR: An unusual case of malignant transformation of a cervical osteochondromas arising from the articular complex, in a young girl affected by HME, and radical surgery is important for the prognosis and to prevent the progression of the lesions.
Abstract: Objectives: Hereditary multiple exosostes (HME) is a disorder characterized by the presence of multiple osteochondromas of the bone. Spinal involvement is rare, represent roughly 3% of cases and any portion of the vertebral body may be affected. Malignant transformation of the lesions is rare, but it is possible and is described in literature. Methods: W e describe an unusual case of malignant transformation of a cervical osteochondromas arising from the articular complex, in a young girl affected by HME. The patient underwent surgery with a complete removal of the lesion, without any signs of recurrence seen at the MRI serial control at 3, 6 12 e 24 months. We analyzed the literature up to 2009 by focusing on the treatment and follow up. Results: Surgical removal is indicated for symptomatic spinal osteochondormas. The suspicion of malignant transformation is indicated by the sudden growth of the lesion after puberty, the presence of pain and the worsening of the neurological symptoms. Conclusion s : In this case, radical surgery is imperative, given the close correlation with the malignant characteristics of the lesions, it is useful to have an extemporaneous histological examination. In the rare cases of malignant transformation, radical surgery is important for the prognosis and to prevent the progression of the lesions. If the complete removal is not possible, the therapy of choice is adjuvant radiotherapy.
TL;DR: An 85-year-old man with hormone refractory prostate cancer was presented with gross hematuria and four months after surgery, PNET of the bladder recurred with rapid growth and the patient died of tumor.
Abstract: We report a rare case of primary primitive neuroectodermal tumor (PNET) of the urinary bladder. An 85-year-old man with hormone refractory prostate cancer was presented with gross hematuria. Abdominal computed tomography showed a tumor occupying the right lateral portion and neck of the bladder wall, while a cystoscopic examination revealed a bleeding, sessile globular tumor with no papillary features. Transurethral resection of the bladder tumor was performed. Histopathological results showed a small round cell tumor forming rosettes, further positive immunoreactivities for some neural markers and MIC gene product (CD99), which indicated PNET of the bladder. Four months after surgery, PNET of the bladder recurred with rapid growth and the patient died of tumor. To our knowledge, there have been only 8 such cases reported.
TL;DR: PFT parameters and other variables versus the development of RILI in patients treated for non-small cell lung cancer by a single radiation oncologist are compared and there is no correlation between PFT values and risk of RilI.
Abstract: Introduction: Radiation-induced lung injury (RILI) is a potentially fatal yet incompletely understood complication following radiation therapy. Models have been posited to predict RILI risk but have produced inconsistent results. Here we evaluate pulmonary function testing (PFT) metrics vs. RILI incidence with the hope of establishing clinical thresholds for RILI risk. Methods: Our study population consisted of adult patients who completed conventionally-fractionated, definitive external beam RT for non-small cell lung cancer in a five-year period (January 1, 2006 to December 31, 2010). All patients were treated by a single radiation oncologist with identical technique, with dose prescriptions ranging from 50.4-74.4 Gray. We collected demographic and treatment variables, pre-radiation PFT values, and ≥ grade III RILI events. Results: There were 62 patients in our dataset. RILI occurred in 6 patients. No significant associations were seen between age, radiation dose, or the use of chemotherapy vs. the development of RILI. Tukey’s plots were constructed for PFT parameters and showed no significant differences in PFT values (absolute or percent of predicted) among RILI vs. non-RILI patients. Conclusions Our study compared pulmonary function parameters and other variables versus the development of RILI in patients treated for non-small cell lung cancer by a single radiation oncologist. We found no correlation between PFT values and risk of RILI. More research is needed to understand better the risks of RILI and to develop a clinically-useful and consistent model for RILI prediction.
TL;DR: Although with low frequency, FISH using a variety of probes can provide precise classification in a few otherwise unclassifiable high grade sarcomas, the findings affirm the utility of FISH technology in FFPE tissues, including small biopsies.
Abstract: Objectives: In an era of rapid advances in oncologic treatment, there is continuous emphasis for a definitive classification of undifferentiated sarcomas in order to select the most appropriate therapeutic regimens against these malignancies. EWSR1, FOXO1A, SS18 and DDIT3 gene break-aparts associated with chromosomal translocations are widely used as specific molecular markers in diagnosing the Ewing family of tumors, alveolar rhabdomyosarcoma, synovial sarcoma and myxoid liposarcoma, respectively. However, the utility of these markers for definitive categorization of previously unclassified high-grade sarcomas has not been studied. Methods: We identified 40 sarcomas from 2003 to 2009, which on light microscopy exhibited a spindle cell or epithelioid morphology with marked nuclear atypia, high mitotic rate and necrosis. These sarcomas were high grade and poorly differentiated, and remained unclassified despite the use of immunohistochemical panels comprising neural, smooth muscle, skeletal muscle, melanocytic, epithelial, vascular and fibrohistiocytic markers. Results: Thirty five cases were resection specimens, and the rest were needle biopsies. Fluorescence in situ hybridization (FISH) was applied to formalin fixed paraffin embedded tissue (FFEP) with break-apart probes for EWSR1, FOXO1A, SS18 and DDIT3 gene. In positive cases, RT-PCR was done to detect specific gene fusions associated with translocations. One of 40 cases was positive for DDIT3 gene break-apart, consistent with a dedifferentiated myxoid liposarcoma. Conclusions: Subsequent reverse transcriptase (RT)-PCR demonstrated a FUS-DDIT3 fusion, supporting the FISH result. Another case was positive for the FOXO1A gene break-apart, consistent with alveolar rhabdomyosarcoma, even though RT-PCR failed to reveal specific gene fusion. Although with low frequency, FISH using a variety of probes can provide precise classification in a few otherwise unclassifiable high grade sarcomas. The findings also affirm the utility of FISH technology in FFPE tissues, including small biopsies.