Purpose: Invasive fungal infections are an important cause of morbidity and mortality in children with febrile neutropenia. Although liposomal amphotericin B (L-AMB) is used safely due to its broad antifungal activity, it causes important side effects such as nephrotoxicity and hypokalemia. Methods: Medical records of 45 children with hematological malignancies who were given empirical L-AMB for febrile neutropenia between November 2011 and December 2019 were reviewed retrospectively. The estimated glomerular filtration rate (eGFR), serum creatinine and potassium levels were compared before and after 7th day of L-AMB treatment. Results: 62 febrile neutropenic attacks of 45 children were evaluated. The median age of the patients was 8.25 (3.5-13) years, and the number of attacks per patient was between 1-5. The median duration of treatment with L-AMB was 14 (range 9-21) days. Nephrotoxicity developed in 16 attacks (26%), and hypokalemia developed in 26 attacks (42%). In those who developed nephrotoxicity, eGFR was lower and creatinine level was higher after 7th day of L-AMB treatment, compared to their values before treatment. The frequency of hypokalemia was low in attacks where nephrotoxicity has been developed. High eGFR, and low creatinine level were risk factors with borderline significance from the point of development of nephrotoxicity. Conclusion: Potassium level should be carefully monitored and appropriate replacement therapy should be administered in febrile neutropenic children with hematological malignancy receiving L-AMB therapy. Parenteral hydration before L-AMB administration does not prevent nephrotoxicity, however it positively affects the frequency of nephrotoxicity.
Glioblastoma multiforme (GBM) is one of the most deadly tumors; even with aggressive radiochemotherapy, mean survival rates are only around 14 to 16 months post diagnose. Here we present the follow-up of 15 patients with GBM that have received concomitant cannabidiol (CBD) in addition to standard therapy, and that have been reported in details two years ago. The survival time of patients is presented together with prognostic factors such as age at diagnose, molecular markers and dose of CBD. The actual median survival time is 28 months, the arithmetic mean is 30.9 months, therefore about three to five times longer than expected. When comparing the group of patients surviving less than 28 months with those who lived longer, we found that all subjects who received a low dose of CBD (200mg per day) were in the group surviving less than 28 months. Apart from the daily dose of CBD, no striking difference was observed for other prognostic factors. It is concluded that CBD contributed to the long term survival of GBM patients, and that this effect depends on the dose.
Most common urinary system cancer is the Bladder cancer(BC), more common in men (M/F: 3), is associated with both genetic and environmental factors.,two most well-known environmental factors are smoking and occupational exposures.Smoking is associated with 25-65% of BC cases, %50 average. Urothelial cancers are common in occupations that use paint, textiles, rubber and petroleum products. Among the chemical substances; O-toluidine, 2-naphthylamine, benzidine, 4-amino-biphenyl and nitrosamines are particularly related with the BC. Our objective in this systematic review is to indicate the value and aid of CT and MRI in the diagnosis of bladder cancer.
Introduction: Oral carcinogenesis is a multistage process, featuring genetic and molecular alterations leading to rapid cell division, invasion, metastasis, and increased cell survival. Many of these alterations are due to perturbations in the cell signaling networks, which in turn lead to constitutive deregulation of the proteins involved in the regulatory pathways. Our recent reports show that the silencing of dentin sialophosphoprotein (DSPP) and its cognate matrix metalloproteinases 20 (MMP20) alters key tumorigenic hallmarks of oral squamous cell carcinoma (OSCC). Objective: This study, intended to advance our recent findings, focuses on determining the effects of silencing DSPP and its cognate MMP20 on the signaling pathways that control cell proliferation, differentiation, invasion and metastasis. Materials and Methods: DSPP and MMP20 were silenced individually and in combination, using adenovirus-mediated short hairpin RNA (shRNA) in OSCC cell line, OSC2, and the effects of silencing on the following pathways: EFGR; RAS-RAF; MEK; MAPK; ERK; JNK; NF-kB; TGFβ; and GSK3β, were analysed by western blot. Results: DSPP and MMP20 silencing decreased EGFR, KRAS, MEK1/2, MAPK, ERK, MEEK1, JNK, CREBP, p300, NF-kB,TGF β, SMAD7, GSK3 β, and β-catenin expressions. In contrast, the expression of IKKα and SMAD4 were increased in DSPP/MMP20-silenced group, compared with control group. Furthermore, DSPP-silencing alone was more effective than MMP20, or combined DSPP-MM20 silencing, in altering the levels of key proteins of each signaling pathway investigated. Conclusion: Our findings provide the basis for further studies aimed at verifying the effects of these alterations in the profiles of these proteins on the various hallmarks of oral carcinogenesis, and for understanding the molecular role of DSPP and MMP20 in OSCC. This is with a view to evaluating their diagnostic and prognostic utility as well as the values of DSPP/MMP20 as potential targets for design of chemotherapeutic agents for the treatment of OSCC patients.
Thymic carcinoma (TC) is a rare epithelial malignancy often distinguished by significant local invasion and propensity for distant metastases. Representing approximately 20% of all thymic neoplasms, the primary therapeutic intervention for resectable tumors remains surgical resection. For those that are unresectable or metastatic, palliative platinum-based chemotherapy is standard. Despite these interventions, approximately 30% of these malignancies are already advanced upon initial presentation. The current 5-year survival rate for metastatic TC stands at approximately 38%, with a definitive optimal treatment regimen yet to be established. This case report delineates a comprehensive five-year clinical trajectory of a patient with advanced TC who exhibited resistance to systemic treatments but showed favorable response to stereotactic body radiation therapy (SBRT). Through this case, we underscore the potential of SBRT as a viable therapeutic alternative for select metastatic TC patients. In our case, SBRT exhibited reliable local tumor control in each treated site with minimal side effects. To better understand the possibility of treatment options for disseminated TC more cases should be collected.
Breast cancer death polls are rising at an alarming rate in females globally. It is a hormone-dependent disease that is majorly regulated by estrogen. Several genetic and environmental factors are the primary attributes of breast cancer growth and development. A higher proportion of breast cancer patients harbor estrogen receptor-positive (ER+ve) status. Estrogen related receptors are orphan nuclear receptors which include ERRα, ERRβ, and ERRϒ that exhibit a sequence similarity with ERα. ERRα and ERRϒ act as activators in cancer. ERRβ expression is downregulated in breast cancer cells and patient samples, compared to healthy breast cells. The decreased expression of ERRβ is primarily mediated by the proteasomal pathway at the protein level. ERRβ restricts cell cycle progression in breast cancer cells, thereby impeding breast cancer proliferation. Neddylation of ERRβ mediates its downregulation which triggers the oncogenic signalling in breast cancer. Our study showed employing MLN4924, an NAE inhibitor to restore the expressivity of ERRβ could provide a successful and cutting-edge therapeutic method. This review article illustrates the regulatory role of ERRβ in the formation and evolution of breast cancer, making it an effective therapeutic candidate.
Objective: To find out the association of large loop excision of the transformation zone (LLETZ) at or less than 36 weeks of gestation, extreme preterm delivery at or less than 28 weeks gestation and perinatal mortality with premature birth. Design: Data was collected from euroking, ‘joe’ and e-searcher systems of 407 retrospective cases. The data were analysed pre and post cervical histology between 20-43 weeks of pregnancy to identify live births. Setting: East Sussex Healthcare Trust Population: The selected population were women who became pregnant after LLETZ treatment at the East Sussex hospital. Their case notes and histology reports were taken into account. The women who were not included in this study were those in age group greater than 42 years, previous premature labour or twin pregnancies. Result: Total number of deliveries in East Sussex hospital in a year were 4349 and the deliveries at term gestation (37 +) were 4057. The total number of all preterm deliveries were 268 (6.16 %), 34 to 36+6 weeks were 198 (4.55 %) and less than 34 weeks were 70 (1.6 %). In 24 cases gestation was unknown. The total data collected were of 407 LLETZ treatment cases. The number of premature deliveries were 45 (11 %) as against background risk of 6.16%. Those who had term pregnancy prior to LLETZ were 15 out of these 45 cases, and the remaining had their first pregnancy after having LLETZ. Conclusion: LLETZ increases the chances of premature births.
Background: P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are the most mysterious class of small non-coding RNAs. They limit gene expression in gonads and sequence diversity. Dysregulated piRNAs can led to all kinds of cancers. Recently, piRNAs were postulated to be potentially useful biomarkers for tumor diagnosis and prognosis. However, there lack a systematic review of prognostic and diagnostic piRNAs in neoplasms. The study aimed to decipher the relationships between piRNAs expression, diagnostic and prognostic outcome in tumors. Methods: This study systematically searched Google Scholar, MEDLINE, Scopus, PubMed, Embase, ScienceDirect, Ovid-Medline, Chinese National Knowledge Infrastructure, WanFang and SinoMed databases for relevant articles published before July 13, 2022. The study is registered in PROSPERO (CRD42020208717). Results: Thirty relevant studies were included in the meta-analysis: 19 on diagnosis and 23 on prognosis. The pooled adds ratio, 95% confidence intervals (Cl) and hazard ratios (HR) of the studies were used to investigate the clinical parameters and overall survival (OS) of cancer patients. The area under the curve (AUC), sensitivity, and specificity was 0.82, 79%, and 77% in tumors, respectively. Though abnormally expressed piRNAs were associated with poor and unfavorable impacts on the OS time of cancer patients (HR=1.00, 95% Cl: 1.00-1.00, P<0.00001). Meanwhile, piRNAs in the breast cancer had favorable impacts on the OS (HR=0.70, 95% CI:0.45-1.09). However, the piRNAs in cell renal cell carcinoma, colorectal cancer, diffuse large B-cell lymphoma and gastric cancer had bad favorable impacts on the OS (HR=1.46, 95% CI:1.37-1.55; HR=1.56, 95% CI:1.24 -1.95; HR=2.19, 95% CI:1.25-3.86; HR=1.01, 95% CI:0.97-1.04, respectively). Conclusions: The results strongly suggested that piRNAs were potential novel prognostic and diagnostic indicators in tumors.
Introduction: DSD are congenital alterations in which either sexual chromosomes, gonadal or anatomical development are atypical. It is estimated that about 1 in every 4500 live births has some type of DSD, ovotesticular DSD representing around 3-10% of the cases. Given the rarity of DSD, it is an underexplored area, and little is known of ovotesticular DSD. Materials and Methods: A retrospective study on patients diagnosed with Ovotesticular DSD in a tertiary medical center from 2009 to 2018. The clinical presentation, phenotype, gonadal features, gender assignment and medical management were evaluated. Results: A total of 184 cases matched the initial search criteria. Only 9 patients with confirmed histopathological diagnosis were selected. Eight out of the nine cases evaluated presented ambiguous genitalia at birth, and only one was detected until pubertal age with presence of bilateral gynecomastia. A female 46 XX karyotype was reported in six patients, whereas the remaining three patients had mosaicism. Four patients were at pubertal age at the time of the study, and three of them required induction of puberty due to lack of sexual steroid production due to loss of gonadal organs. Discussion: Ovotesticular DSD is a rare finding with a heterogeneous spectrum concerning its genetic etiology, clinical presentation, and surgical findings. Most patients are diagnosed during infancy or childhood; few are diagnosed at pubertal age. Conclusion: Actual management and decision on gender assigning and treatment is challenging and debatable; therefore, a scrupulous clinical examination, as well as hormonal, imaging, genetic and molecular investigation is needed for a correct diagnosis. Further investigation is required to fully understand the disease.
Hepatocellular carcinoma (HCC) is a common cancer with high incidence rate, and 5-year survival rate in HCC is less than 20%. Thus, in search of newer anticancer agents effective in HCC, we have explored possible usefulness of an alternative medicine Lycopodium against the human liver cancer cell line, HepG2 along with its clinical efficacy. The HepG2 cell line was challenged with Lycopodium 6C (diluted Lycopodium <1pg /mL available as alternative medicine) along with vehicle alcohol control in 24 hours. The cytopathic effect and viability test with methylene blue stain were observed. The cells were harvested for total RNA extraction, and gene expression levels of targeted cytokines -Interferon gamma (IFN γ); Interleukins - IL-6, IL-8, IL-10, IL-1β, Transforming Growth Factor- TGF-β1, TGF-β3 and Tumor Necrosis Factor alpha (TNF-α) by RT-PCR were studied. DNA fragmentation assay and cell viability assay by MTT method were also tested. After ethical permission we applied this medicine as adjunct therapy to observe any beneficial role of the medicine. Statistically significant changes of IL-10, IL-1β and TGF-β3 were observed after challenge with Lycopodium 6C. The IL-10 gene expression in malignant cells was significantly reduced with Lycopodium 6C; however, the expression is more with vehicle alcohol compared to normal control set. Thus, the medicine could decrease the excessive IL-10 gene expression to a moderate level. IL-1β and TGF-β3 gene up-regulation by the vehicle alcohol were also mitigated by the medicine Lycopodium 6C. Mild DNA fragmentation was also seen in cancer cells after challenge with the medicine. Two cases suffering from hepatocellular carcinoma showed much clinical improvement after therapy with this medicine. Lycopodium 6C may act as a supporting alternative medication for treating HCC.
Objective: To analyse clinical characteristics of adult patients with acute lymphoblastic leukemia (ALL) and explore prognostic factors to provide evidence for the stratification of prognostic risk and the formulation of individualized therapy. Methods: A total of 65 adult patients with newly diagnosed ALL were reviewed. Their clinical data were collected, and their overall survival was followed up. We compared the effects of different clinical features on therapeutic efficacy and long-term prognosis. Data analysis was conducted by SPSS 25.0 statistical software. P < 0.05 was considered statistically significant. Results: A total of 65 adult patients with newly diagnosed ALL, including 31 males and 34 females, were enrolled in this study, with a median onset age of 48 (range, 18-85) years. After 1 course of induction therapy, bone marrow puncture was performed to evaluate, and further demonstrate that 49 patients achieved complete response (CR), with a total CR rate (CRR) of 75.4%. Among 65 patients, the median overall survival was 15.5 (range,1.0-100.0) months, and the median disease-free survival was 9.0 (range, 0.0-99.0) months. Survival analysis showed that worse long-term outcome was associated with age (≥60 years), haemoglobin (Hb<60g/L), platelet (PLT<30×109/L), lactic dehydrogenase (LDH≥400U/L) at initial diagnosis, CD10 negative, and failure to reach CR within 4 weeks after induction therapy, whereas timely hematopoietic stem cell transplantation (HSCT) significantly improved the survival of patients. Univariate analysis suggested that age at onset, the initial level of low PLT and high LDH, and HSCT were risk factors for 2-year OS and 2-year DFS of adult ALL patients. Moreover, multivariate analysis showed that initial PLT level was an independent risk factor for the prognosis of adult ALL patients, and CR within 4 weeks after induction and HSCT could improve patients’ overall survival. Conclusion: Long-term outcome for adult ALL patients is poor. Clinical characteristics, including elder age, severe anemia, low PLT level, high LDH level, CD10 negative and so on, make poor clinical induction effect on such patients. However, achieving CR within 4 weeks and actively accepting HSCT can significantly improve the prognosis of adult ALL.
Objective: Assessment of a volumetric method versus gold standard unidimensional measurement based on RECIST 1.1 in advanced renal clear cell carcinoma (RCC) treated by immunotherapy. Materials and Methods: We retrospectively recorded the CT data of 14 adult patients treated with immunotherapy for metastatic RCC from February 2016 to January 2018. Follow-up CT scanners were independently reviewed by two radiologists. Unidimensional RECIST 1.1 and volumetric measurements were compared at each time point, with a total of 810 measurements performed for statistical analysis. The main criterion was the inter-observer agreement for each method. The secondary criterion was the tumoral response assessment based on three different items: RECIST 1.1, spherical volumetric method, ellipsoidal volumetric method. Results: Intraclass coefficient correlation in volumetric method (0.986 [95% CI: 0.980, 0.990]) was higher than in RECIST (0.903 [95% CI: 0.861, 0.928]). Relative measurement differences with Bland and Altman plot were lower in the volumetric method with shorter limits of agreement (0.8%; upper LOA95%: 36.5; lower LOA95%: −35), versus those in RECIST (-5.1 % (upper LOA95%: 46; lower LOA95%: −57). The volumetric method (especially the ellipsoidal one) assesses the progression disease earlier than RECIST for 57% of patients, but there is no formal difference for partial response assessment. Conclusion: Volumetric assessment for tumoral response in metastatic RCC compared to unidimensional measurements had a higher inter-observer agreement and might predict disease progression earlier.
Background: Coronavirus disease (COVID-19) was declared as pandemic by World Health Organization (WHO) on 30th January 2020. Cancer patients are a vulnerable population with increased risk for mortality associated with COVID-19 infection. In this study, we report the impact of education for acceptance of COVID-19 vaccination in our cancer patients. Methods: This was a cross-sectional study between 1st August 2021 and 31st October 2021. All patients with diagnosis of cancer who presented to the oncology clinic were asked whether they received COVID-19 vaccine or planning to get vaccinated. Patients, who had refused the vaccine, were educated to get vaccinated. Post counseling, they were again asked if they would agree to get vaccinated. Results: Out of 512 cancer patients, 274 (53.5%) were male. Of total, 456 (89.1%) were diagnosed cases of solid malignancy. Patients who were on active oncological treatment were 406 (79.3%). Of total 512, 396 (77.3%) patients agreed for the COVID-19 vaccine while 116 (22.7%) had refused to get vaccinated. Of those 116, 75 (64.7%) patients accepted to get vaccinated post counseling. Conclusion: COVID-19 vaccine acceptance is higher among cancer patients at our institute compared to reported data. Oncologists should play a key role in encouraging their patients to get vaccine in order to reduce COVID-19 related mortality.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. It is located mainly in the head and neck, extremities and trunk, rarely achieving the biliary tract (1%). The clinical presentation is characterized by obstructive jaundice, abdominal pain and palpable mass. The prognosis is favourable when being early diagnosed. The main differential diagnosis is the choledochal cyst. We bring a case report about a patient with biliary tract rhabdomyosarcoma, diagnosed and treated for 1 year as choledochal cyst, presenting obstructive jaundice for one year. A hepatic biopsy was done, showing hepatic fibrosis. He presented clinical worsening and was referred for liver transplant. An exploratory laparotomy was done before planning the transplant, which showed a biliary tract mass, followed by a biopsy. The anatomopathological result was RMS. Biliary tract RMS is a rare entity that should be included in the differential diagnosis of obstructive jaundice in children. Because of its similarity with choledochal cyst, pediatricians and surgeons should consider this hypothesis, for adequate investigation and treatment.
Background: After the Fukushima Nuclear Power Plant accident in 2011, thyroid ultrasound screening was carried out as part of the Fukushima health management survey (FHMS) on all residents of ages≤18 years at the accident. The results of the 1st (2011-2013) and 2nd (2014-2015) round screening showed dozens of times excess thyroid cancer detection compared to the expected from the cancer registry. Both FHMS and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) summarized that thyroid cancer cases detected in Fukushima were unlikely to be attributed to radiation exposure from the absence of dose-response relation. We elucidated the response of thyroid cancer incidence to individual external doses and found the dominant radiation effect on the increased thyroid cancer incidence after the accident. Method: Association between average individual external dose based on FHMS basic survey and thyroid cancer incidence rate of dose groups was analysed by the linear regression analysis. Thyroid dose estimated in UNSCEAR 2020/2021 for 10-year-old children was used for comparison. Results: Incidence proportions of dose groups in the 2nd round showed a linear response to mean individual external dose under 2.5 mSv range. A rough estimate of the excess relative risk per gray (Gy) was ERR/Gy =213 (95%CI: 129, 297) (p=0.02). Conclusion: Childhood and adolescent thyroid cancer in Fukushima was associated with individual external dose estimated in FHMS basic survey. Increased childhood and adolescent thyroid cancer in Fukushima could most probably be attributed to radiation exposure from the nuclear accident.
Gastric cancer still threatens the health of people, which is the fifth most common cancer and the fourth leading cancer-related death worldwide. The stage of the disease is critical for the 5-year survival of gastric cancer; the 5-year survival rates could reach 90% for gastric cancer detected at early stages. At present, endoscopic submucosal dissection (ESD) is the main treatment for early gastric cancer. Referring to the treatment guideline of the Japan Gastric Cancer Association, the indications for ESD mainly include absolute indications, expanded indications, and relative indications. Many studies have reported favourable long-term outcomes after undergoing ESD, and compared with surgery, ESD preserves the entire stomach and improves the quality of life of patients. However, it has also been reported that the recurrence rate of gastric cancer after ESD is high, so regular follow-up and careful examination are needed, even for patients with early gastric cancer who met absolute indications.
As a highly heterogeneous disease, diffuse large B-cell lymphoma shows different clinical presentations, molecular and immunophenotypic characteristics, International Prognostic Index (IPI score) and response to therapy, which consequently brings about different prognoses and survival results. In addition to surgery and chemotherapy, radiation is also one important modality to treat diffuse large B-cell lymphoma. Over the past few decades, radiation therapy has stepped forward because of technological revolutions. The role of radiation in treating diffuse large B-cell lymphoma is discussed, including: i) advances in modern-day radiation technology ii) potential toxicity from radiation, iii) indications for radiation, and iv) available studies about the efficacy of radiation.
Hemophagocytic lymphohistiocytosis (HLH) may be secondary to cancer or other conditions in adults. We aimed to compare characteristics and outcomes of secondary HLH depending on cancer status among adults. Weight loss over 10 %, headache and enlarged lymph nodes were more frequent in malignant- HLH (M-HLH). Higher phosphatase alkaline level and CRP level were present in M-HLH. Mortality rate tended to be higher in M-HLH group in the first month and during the two years follow-up. Some clinical features and biological abnormalities are associated with an increased probability of malignancy in secondary HLH among adults.
Background: Thyroid cancer incidence of individual dose groups in Fukushima residents exposed at ≤18 years of age demonstrated a linear response to thyroid dose estimated in the United Nations Scientific Committee on the effects of Atomic Radiation (UNSCEAR) 2020/2021. Increased childhood thyroid cancer in Fukushima was found to come dominantly from radiation exposure from the nuclear accident. The UNSCEAR 2020/2021 concluded that the apparent excess of thyroid cancers would not be expected at thyroid doses estimated by the UNSCEAR. The purpose of this paper is to solve the puzzle of the high childhood thyroid cancer incidence in Fukushima despite the estimated low thyroid dose. Methods: The conversion coefficient k connecting thyroid doses estimated in UNSCEAR 2020/2021 and doses based on direct thyroid dose measurements in Chernobyl: 1 GyUN2021 = k × 1 Gy (gray), was estimated by comparing incidences and dose dependences of thyroid cancers in Fukushima and Chernobyl after nuclear disasters. Results: The ratio of the observed cases /expected cases from cancer registry: of about 60 in Fukushima prefecture, was higher than the ratios observed after the Chernobyl accident. The thyroid doses estimated by UNSCEAR were corrected by adding a baseline dose to recover the severely underestimated ingestion dose. The conversion coefficients were: k =60~70 from the comparison of the excess absolute risks (EAR) and their dose dependences in Fukushima and in Chernobyl, and k =10~180 from the comparison of excess relative risk per gray (ERR/Gy) in Fukushima with those in Chernobyl. The thyroid doses might have been underestimated by about 1/50~1/100 in UNSCEAR 2020/2021. Conclusion: The dozens-fold increase of childhood thyroid cancer cases after the Fukushima nuclear accident was found to arise from radioactive iodine exposure comparable to that in Chernobyl.
Introduction: Many advances have emerged in the management of peritoneal metastases of ovarian cancer origin, widely known as the most common gynaecological malignancy. This review is an update of the current management algorithm of peritoneal carcinomatosis of ovarian cancer, including screening methods, biomarkers and surgical techniques, in an effort to shed some light into this difficult to treat malignancy. Objective: To assess awareness in the management of epithelial ovarian cancer (EOC) with peritoneal metastasis with updated therapeutic standpoints.
