Management Of Malignant Disease Research Articles

Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers.

Liquid biopsies are revolutionizing the detection and management of malignant diseases. While repetitive DNA sequences, such as LINE-1 and ALU are established in cell-free DNA (cfDNA) research, their clinical applications remain limited. In this study, we explore human satellite 2 (HSATII), a prevalent repeat DNA sequence in plasma that exhibits increased levels in cancer patients, thereby positioning it as a potential pan-cancer biomarker. We employed targeted sequencing and copy number variation (CNV) analysis using two primer pairs to assess the differential abundance of HSATII sequences in the plasma of breast cancer patients compared to healthy individuals. PCR amplicons of HSATII from 10 patients and 10 control subjects were sequenced, generating 151 bp paired-end reads. By constructing a pooled reference dataset, HSATII copy ratios were estimated in the patients. Our analysis revealed several significant CNVs in HSATII, with certain sequences displaying notable gains and losses across all breast cancer patients, suggesting their potential as biomarkers. However, we observed pronounced fragmentation of cfDNA in cancer, leading to the loss of longer PCR amplicons (>180 bp). While not all observed losses can be attributed to fragmentation artifacts, this phenomenon does introduce complexity in interpreting CNV data. Notably, this research marks the first instance of targeted HSATII sequencing in a liquid biopsy context. Our findings lay the groundwork for developing sequencing-based assays to detect differentially represented HSATII sequences, potentially advancing the field of minimally-invasive cancer screening.

Phenotypic Analysis of Hematopoietic Stem and Progenitor Cell Populations in Acute Myeloid Leukemia Based on Spectral Flow Cytometry, a 20-Color Panel, and Unsupervised Learning Algorithms.

The analysis of hematopoietic stem and progenitor cell populations (HSPCs) is fundamental in the understanding of normal hematopoiesis as well as in the management of malignant diseases, such as leukemias, and in their diagnosis and follow-up, particularly the measurement of treatment efficiency with the detection of measurable residual disease (MRD). In this study, I designed a 20-color flow cytometry panel tailored for the comprehensive analysis of HSPCs using a spectral cytometer. My investigation encompassed the examination of forty-six samples derived from both normal human bone marrows (BMs) and patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) along with those subjected to chemotherapy and BM transplantation. By comparing my findings to those obtained through conventional flow cytometric analyses utilizing multiple tubes, I demonstrate that my innovative 20-color approach enables a more in-depth exploration of HSPC subpopulations and the detection of MRD with at least comparable sensitivity. Furthermore, leveraging advanced analytical tools such as t-SNE and FlowSOM learning algorithms, I conduct extensive cross-sample comparisons with two-dimensional gating approaches. My results underscore the efficacy of these two methods as powerful unsupervised alternatives for manual HSPC subpopulation analysis. I expect that in the future, complex multi-dimensional flow cytometric data analyses, such as those employed in this study, will be increasingly used in hematologic diagnostics.

Real-world clinical effectiveness of sorafenib among patients with unresectable hepatocellular carcinoma at two centers in the United States.

In the United States, sorafenib monotherapy was approved in 2007 for first-line (1L) treatment of patients with unresectable hepatocellular carcinoma (uHCC). As other therapies have been approved in recent years for hepatocellular carcinoma treatment in later lines, it is essential to assess clinical effectiveness of older therapies in actual clinical practice to inform healthcare practitioners' decisions for better patient care. To assess patient characteristics/clinical effectiveness of 1L sorafenib in uHCC patients treated in United States academic and community practice settings. A retrospective observational study was conducted among adult patients (≥ 18 years) in the United States initiating sorafenib monotherapy as 1L systemic therapy for uHCC with Eastern Cooperative Oncology Group status of 0 or 1 between January 2016 and December 2019 at City of Hope and Advent Health. Data were extracted by trained abstractionists from individual patients' electronic health records and captured in electronic case report forms. Institutional Review Board approvals were obtained prior to study initiation. Data were captured from the time of sorafenib initiation until death or the end of follow-up. All data were de-identified prior to analyses. Clinical outcomes assessed included provider-reported best response, progression-free survival (PFS), and overall survival (OS). PFS and OS were estimated using Kaplan-Meier methods. Among 134 uHCC patients treated with 1L sorafenib, majority were male (75%), and most were Caucasian (62%) or Asian (19%). Median patient age was 64 years. The most common etiologies of liver disease were hepatitis C (54%), alcohol-related liver disease (16%), and hepatitis B (11%). Most patients were reported to have Barcelona Clinic Liver Cancer stage B (19%) or stage C (70%) disease. Of 134 patients, 110 (82%) were reported to have discontinued treatment or died during follow-up. Primary reasons for sorafenib discontinuation were reported as progression (35%) and toxicity (30%). Best overall response was reported for 124 patients, of which 7.3% reported complete or partial response. Median time to treatment discontinuation was 2.3 mo. Overall, 103 patients (77%) had disease progression or died during sorafenib therapy. Median PFS was estimated to be 2.9 mo. At the end of follow-up, 82 patients (61%) were deceased. Median OS was 8.5 mo. Newer therapeutic options that have reported higher PFS and OS in real-world clinical practice should be considered to enhance patient outcomes.

Pomolic acid and its glucopyranose ester promote apoptosis through autophagy in HT-29 colon cancer cells.

Colon cancer remains a leading cause of death globally. Pomolic acid (PA) can be separated from the ethyl acetate fraction of achyrocline satureioides. To determine the effects of PA and its glucopyranose ester, pomolic acid-28-O-β-D-glucopyranosyl ester (PAO), on colon cancer HT-29 cells. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to measure cell viability. Apoptosis was detected via hoechst 33342 staining. PI single staining was identified by flow cytometry to determine the cycle and scratch assay was used to observe the migration of HT-29 cells. The levels of mRNA and proteins were evaluated by q polymerase chain reaction and western blotting, respectively. PA and PAO considerably inhibited the growth of the HT-29 cell line in a time and dose-dependent manner. After the administration of PA and PAO for 24 and 48 h, cell apoptosis was significantly promoted and HT-29 cells were arrested in the G0/G1 stage. The Bax/Bcl2 ratio was also increased, which activated cysteinyl aspartate specific proteinase 3, leading to apoptosis; it also increased the expression of light chain 3 II/I and Beclin1, which activated autophagy and caused cell death. This in turn increased the expression of p62 to promote cell apoptosis, inhibiting the levels of signal transducer and activator of transcription 3 (STAT3) and p-STAT3, suppressing the level of Bcl2, and promoting cell. Both PA and PAO provide novel therapeutic strategies for treating colorectal cancer.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature

Minimally invasive surgery is increasingly indicated in the management of malignant disease. Although oesophagectomy is a difficult operation, with a long learning curve, there is actually a shift towards the laparoscopic/thoracoscopic/ robotic approach, due to the advantages of visualization, surgeon comfort (robotic surgery) and the possibility of the whole team to see the operation as well as and the operating surgeon. Although currently there are still many controversial topics, about the surgical treatment of patients with gastro-oesophageal junction (GOJ) adenocarcinoma, such as the type of open or minimally invasive surgical approach, the type of oesophago-gastric resection, the type of lymph node dissection and others, the minimally invasive approach has proven to be a way to reduce postoperative complications of resection, especially by decreasing pulmonary complications. The implementation of new technologies allowed the widening of the range of indications for this type of surgical approach. The short-term and long-term results, as well as the benefits for the patient - reduced surgical trauma, quick and easy recovery - offer this type of surgical treatment the premises for future development. This article reviews the updates and perspectives on the minimally invasive approach for GOJ adenocarcinoma.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study.

The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited. To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity. Data from Dryad database were used in this study. Patients in the Gastroenterology Department of Sapporo General Hospital, Sapporo, Japan, were enrolled. The starting and ending dates of the enrollment were January 1, 2008 and January 5, 2015, respectively. The cutoff date for follow-up was May 31, 2016. The independent and dependent (target) variables were the baseline measured using the KRS and final all-cause mortality, respectively. The KRS was categorized into three groups: Low-risk group (= 0 score), intermediate-risk group (1-2 score), and high-risk group (≥ 3 score). Men and patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS. The higher the score, the higher the risk of early death; however, the relevance of this independent prediction decreased with longer survival. The overall survival of each patient was recorded via real-world follow-up and retrospective observations, and this study yielded the overall relationship between KRS and all-cause mortality. The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years; however, this independent predictive relationship weakened as survival time increased.

Systemic treatment for advanced pancreatic cancer.

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection. Despite numerous years of research and pharmaceutical development, these figures have not changed. Treatment options for advanced pancreatic cancer are still limited. This illness is typically detected at a late stage, making curative surgical resection impossible. Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy. Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities; these therapies also hold promise for pancreatic cancer. There is an urgent need for research into targeted treatment, immunotherapy, and cancer vaccines. In this review, we emphasize the foundational findings that have fueled the therapeutic strategy for advanced pancreatic cancer. We also address current advancements in targeted therapy, immunotherapy, and cancer vaccines, all of which continue to improve the clinical outcome of advanced pancreatic cancer. We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy.

Modified albumin-bilirubin (mALBI) grade has been established as a survival determinant in hepatocellular carcinoma (HCC) patients who receive locoregional and targeted therapies. To investigate whether mALBI could predict survival in unresectable HCC (uHCC) patients who were treated with atezolizumab plus bevacizumab (AB). A single-center, retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023. An association between mALBI and patient survival was determined using Cox proportional hazards analysis. Of the 83 patients, 67 patients (80.7%) were male with the mean age of 60.6 years. Among them, 22 patients (26.5%) were classified as Barcelona Clinic Liver Cancer B, and 61 patients (73.5%) were classified as Barcelona Clinic Liver Cancer C. Cirrhosis was present in 76 patients (91.6%), with 58 patients classified as Child-Turcotte-Pugh (CTP) A and 18 as CTP B. The median overall survival (OS) and progression-free survival were 13.0 mo [95% confidence interval (CI): 5.2-20.8] and 9.0 mo (95%CI: 5.0-13.0), respectively. The patients were divided into two groups based on mALBI grades: 42 patients (50.6%) in the mALBI 1 + 2a group; and 41 patients (49.4%) in the mALBI 2b + 3 group. During the median follow-up period of 7.0 mo, the mALBI 1 + 2a group exhibited significantly better survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 3.0 mo (95%CI: 0.1-6.0, P < 0.001). In a subgroup of patients with CTP A, the mALBI 1 + 2a group also showed significantly longer survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 6.0 mo (95%CI: 3.4-8.6, P < 0.001). In the multivariate analysis, both CTP class and mALBI grade were independently associated with survival, with adjusted hazard ratios (95%CI) of 2.63 (1.19-5.78, P = 0.020) and 3.90 (1.71-8.90, P = 0.001), respectively. mALBI grades can determine survival of uHCC patients receiving AB treatment, particularly those who have mildly impaired liver function. This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Minimally invasive surgery for gastro-oesophageal junction adenocarcinoma: Current evidence and future perspectives

Minimally invasive surgery is increasingly indicated in the management of malignant disease. Although oesophagectomy is a difficult operation, with a long learning curve, there is actually a shift towards the laparoscopic/thoracoscopic/ robotic approach, due to the advantages of visualization, surgeon comfort (robotic surgery) and the possibility of the whole team to see the operation as well as and the operating surgeon. Although currently there are still many controversial topics, about the surgical treatment of patients with gastro-oesophageal junction (GOJ) adenocarcinoma, such as the type of open or minimally invasive surgical approach, the type of oesophago-gastric resection, the type of lymph node dissection and others, the minimally invasive approach has proven to be a way to reduce postoperative complications of resection, especially by decreasing pulmonary complications. The implementation of new technologies allowed the widening of the range of indications for this type of surgical approach. The short-term and long-term results, as well as the benefits for the patient - reduced surgical trauma, quick and easy recovery - offer this type of surgical treatment the premises for future development. This article reviews the updates and perspectives on the minimally invasive approach for GOJ adenocarcinoma.

Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report

Minimally invasive surgery is increasingly indicated in the management of malignant disease. Although oesophagectomy is a difficult operation, with a long learning curve, there is actually a shift towards the laparoscopic/thoracoscopic/ robotic approach, due to the advantages of visualization, surgeon comfort (robotic surgery) and the possibility of the whole team to see the operation as well as and the operating surgeon. Although currently there are still many controversial topics, about the surgical treatment of patients with gastro-oesophageal junction (GOJ) adenocarcinoma, such as the type of open or minimally invasive surgical approach, the type of oesophago-gastric resection, the type of lymph node dissection and others, the minimally invasive approach has proven to be a way to reduce postoperative complications of resection, especially by decreasing pulmonary complications. The implementation of new technologies allowed the widening of the range of indications for this type of surgical approach. The short-term and long-term results, as well as the benefits for the patient - reduced surgical trauma, quick and easy recovery - offer this type of surgical treatment the premises for future development. This article reviews the updates and perspectives on the minimally invasive approach for GOJ adenocarcinoma.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development.

mRNA vaccines have been investigated in multiple tumors, but limited studies have been conducted on their use for hepatocellular carcinoma (HCC). To identify candidate mRNA vaccine antigens for HCC and suitable subpopulations for mRNA vaccination. Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas. Genes with somatic mutations and copy number variations were identified by cBioPortal analysis. The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis. The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells (APCs). Tumor-associated antigens were overexpressed in tumors and associated with prognosis, genomic alterations, and APC infiltration. A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes. The weighted gene coexpression network analysis (WGCNA) was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines. AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 were identified as candidate HCC antigens for mRNA vaccine development. Four immune subtypes (IS1-IS4) and five immune gene modules of HCC were identified that were consistent in both patient cohorts. The immune subtypes showed distinct cellular and clinical characteristics. The IS1 and IS3 immune subtypes were immunologically "cold". The IS2 and IS4 immune subtypes were immunologically "hot", and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes. IS1-related modules were identified with the WGCNA algorithm. Ultimately, five hub genes (RBP4, KNG1, METTL7A, F12, and ABAT) were identified, and they might be potential biomarkers for mRNA vaccines. AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development. The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination. RBP4, KNG1, METTL7A, F12, and ABAT are potential biomarkers for mRNA vaccines.

Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling.

As an active ingredient derived from Dioscorea zingiberensis C.H. Wright, deltonin has been reported to show anti-cancer effects in a variety of malignancies. To investigate the role and mechanism of action of deltonin in promoting gastric carcinoma (GC) cell apoptosis and chemosensitivity to cisplatin. The GC cell lines AGS, HGC-27, and MKN-45 were treated with deltonin and then subjected to flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide assays for cell apoptosis and viability determination. Western blot analysis was conducted to examine alterations in the expression of apoptosis-related proteins (Bax, Bid, Bad, and Fas), DNA repair-associated proteins (Rad51 and MDM2), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/AKT/mTOR) and p38-mitogen-activated protein kinase (MAPK) axis proteins. Additionally, the influence of deltonin on GC cell chemosensitivity to cisplatin was evaluated both in vitro and in vivo. Deltonin treatment weakened viability, enhanced apoptosis, and dampened DNA repair in GC cell lines in a dose-dependent pattern. Furthermore, deltonin mitigated PI3K, AKT, mTOR, and p38-MAPK phosphorylation. HS-173, an inhibitor of PI3K, attenuated GC cell viability and abolished deltonin inhibition of GC cell viability and PI3K/AKT/mTOR and p38-MAPK pathway activation. Deltonin also promoted the chemosensitivity of GC cells to cisplatin via repressing GC cell proliferation and growth and accelerating apoptosis. Deltonin can boost the chemosensitivity of GC cells to cisplatin via inactivating p38-MAPK and PI3K/AKT/mTOR signaling.

Review on Multiple Cancer Disease Prediction And Identification using Machine Learning Techniques

Abstract: Cancer has been described as a diverse illness with a wide range of subgroups. Early cancer diagnosis and prognosis are essential for clinical patient treatment, which has become a requirement in cancer research. Numerous research teams from the biomedical and bioinformatics fields have studied the use of machine learning (ML) techniques due to the significance of categorising cancer patients into high or low risk groups. These methods have been applied in an effort to simulate the development and management of malignant diseases. Additionally, the importance of ML tools is demonstrated by their capacity to recognise important elements in complex datasets. Artificial Neural Networks (ANNs), Bayesian Networks (BNs), Support Vector Machines (SVMs), and Decision Trees (DTs) are a few of the methods that have been widely used in cancer research to construct prediction models that enable precise and effective decision-making. Although it is clear that applying ML techniques can enhance our comprehension of how cancer progresses, more validation is required before these techniques can be used in routine clinical practise. Advance ML techniques are used in this work to mimic the detection of cancer in numerous human bodily organs, including the brain, breast, and lung.

NCCN Guidelines® Insights: Hematopoietic Cell Transplantation, Version 3.2022.

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

Simple SummaryCirculating tumor DNA (ctDNA) is increasingly employed in the management of malignant diseases, though the implementation of ctDNA diagnostics in daily oncology care has limitations. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using an optimized multiplex PCR-based NGS protocol. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy, endocrine therapy, or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and during therapy. We detected traceable mutations in approximately two-thirds of the cases, and, importantly, new pathogenic variants in follow-up plasma that were not present in the primary tumor and baseline plasma. Our results indicate that ctDNA monitoring during treatment and follow-up with the BC-monitor tool, by predicting disease progression four–six months earlier than conventional methods and supporting treatment decision, may improve the outcome significantly.Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and continuously during therapy. Traceable mutations of the used 38-plex NGS assay were found in approximately two-thirds of the patients. Importantly, we detected new pathogenic variants in follow-up plasma samples that were not detected in the primary tumor and baseline plasma samples. We proved that the BC-monitor can pre-indicate disease progression four–six months earlier than conventional methods. Our study highlights the need for well-designed ctDNA monitoring during treatment and follow-up, integrated into a real-time treatment assessment, which could provide information on the active tumor DNA released into the blood.

A Review on Clinical Outcomes of Pancreaticoduodenectomy in Octogenarian Patients

Management of malignant diseases in elderly patients has been a global clinical issue because of increased life expectancy worldwide. Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. Surgical resection is the only potentially curative treatment for pancreatic cancer. Resection of the pancreas, either by pancreaticoduodenectomy (PD) or laparoscopic pancreaticoduodenectomy (LPD) is a complex surgical procedure with a high rate of morbidity and mortality. However, mortality rates after pancreatic surgery have dropped to less than 2-5% at experienced centers. Whereas, complication rates are high, reaching at least 30% in many centers. Mortality also increases proportionally with age viz. 6.7% of patients aged 65-69 years, 9.3% of patients aged 70-79 years, and 15.5% of patients aged 80 years or older. The present review article delineates clinical outcomes along with safety, morbidity and mortality after PD or LPD in elderly, especially in octogenarian patients.

Herpes zoster infection mimicking pelvic lymph node metastasis on FDG-PET/CT in a patient with cervical cancer.

Although 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is an established method for the staging of malignancies, benign lesions (e.g, active inflammatory lesions) often show increased metabolic activity. Herpes zoster is the clinical manifestation of the activation and replication of dormant varicella-zoster virus (VZV) in individuals with decreased cell-mediated immunity. Although the diagnosis of herpes zoster is clinical, it is sometimes observed incidentally during imaging for another disease. We describe the case of a 67-year-old Japanese female patient diagnosed with cervical cancer in whom FDG-PET/CT revealed herpes zoster manifestations: hypermetabolic cutaneous lesions in the buttock and pelvic lymph node involvement. The resected lymph nodes showed no malignant lesions but revealed lymphoid follicle formation, probably related to viral infection. There has been no report comparing FDG-PET findings of lymph nodes with histologic findings; the present findings are compatible with a clinically VZV-induced inflammatory reaction in regional lymph nodes, which increased FDG accumulation. Active infection with VZV displays increased FDG uptake in regional lymph nodes and may lead to incorrect malignant disease management in oncology. Misdiagnoses can be avoided by a careful interpretation by experienced nuclear medicine physicians as well as proper clinical evaluation.

Time course effects of methotrexate on renal handling of water and electrolytes in rats. Role of aquaporin-2 and Na-K-2Cl-cotransporter

Methotrexate (MTX) is a derivate of folic acid, commonly used as an anchor drug for the treatment and management of malignant diseases and autoimmune disorders. However, nephrotoxicity is an important drawback of MTX therapy. Unfortunately, there are not enough studies reporting the nature of the renal failure induced by MTX. Thus, the aim of this study was to evaluate the time course of renal handling of water and electrolytes in male Wistar rats, after the exposure to a unique dose of MTX (80 mg/kg b.w.). Experiments were carried out at day 2, day 4, day 8 and day 14 after MTX administration. Several parameters of kidney function related to water and electrolytes handling were evaluated. Renal expression and urinary excretion of aquaporin-2 (AQP2) and Na-K-2Cl-cotransporter (NKCC2) were determined by Western blotting. MTX produced alterations on water handling on the second day after treatment, showing a significant increase in solute free water reabsorption which might be mediated by the increased expression of AQP2 in apical membranes. On the other hand, MTX produced alterations on electrolytes handling on the fourth day after treatment, showing a significant decrease of sodium chloride excretion, mediated at least in part, by the increase renal expression of NKCC2. These results provide valuable information to clinical practice in order to be able to find therapeutic targets that diminish adverse effects and health deterioration. Moreover, MTX treatment altered AQP2 and NKCC2 urinary excretion allowing postulating these transporters as potential biomarkers of MTX induced nephrotoxicity.

Malignant Diseases in Pregnancy - Ethical, Diagnostic and Treatment Challenge

Abstract The biological uniqueness of malignant tumors in pregnancy lies in the combination of uncontrolled growth of malignant tumors and controlled growth of fetoplacental complex in the same host. The risk of pregnancy associated with a malignant disease is approximately 0.1% (1 case per 1, 000 deliveries). According to results from one of the largest studies of malignant tumors in pregnancy, which involved almost thousand cases, the most frequent types were breast and cervical cancer, then melanoma, lymphoma and leukemia, gastric and rectal cancer, bone sarcoma and other sarcomas of the soft tissue. According to a Swedish retrospective study on cancer during pregnancy, the incidence rate is 37.4 cases per 100 000 deliveries. Pregnancy-associated malignant disease brings a range of specific problems, such as: difficulties related to diagnosis and staging of the disease; the risk of performing diagnostic and therapeutic procedures during pregnancy; counseling and treatment plan of pregnant women having malignant disease. The treatment plan of a pregnant patient with cancer has three possibilities: termination of pregnancy; postponement of treatment to reach fetal viability; treatment during pregnancy. The management of malignant disease during pregnancy may be highly dangerous or even fatal for the fetus. The treatment includes surgery, radio and chemotherapy. In malignant diseases during pregnancy, the prognosis is the same as in general population cancers of the same stage, localization and type. Termination of pregnancy is indicated in cases of, either high absorbed fetal radiation dose, or high grade, aggressive or metastatic cancer.

The American Society of Clinical Oncology's Efforts to Support Global Cancer Medicine.

Despite much progress in the management of malignant diseases, the number of new cases and cancer-related deaths continues to rise around the world. More than half of new cases occur in economically developing countries, where more than two thirds of cancer deaths are expected. However, implementation of all necessary steps to accomplish the dissemination of state-of-the-art prevention, diagnosis, and management will require increased allocation of resources, and, more importantly, harmonization of the efforts of hundreds of national and international public health agencies, policy-setting bodies, governments, pharmaceutical companies, and philanthropic organizations. More than 30% of the members of the American Society of Clinical Oncology (ASCO) reside and practice outside US borders, and more than half of attendees at all of the scientific congresses and symposia organized by ASCO are international. As cancer has become an increasingly global disease, ASCO has evolved as a global organization. The ASCO Board of Directors currently includes members from France, Brazil, and Canada. In 2013, the ASCO Board of Directors identified a number of strategic priorities for the future. Recognizing the importance of non-US members to the society, their first strategic priority was improving the society's service to non-US members and defining these members' identity in the international oncology community. This article reviews current ASCO activities in the international arena and its future plans in global oncology.