Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin’s lymphoma

To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin’s lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 μmol/L to 58 μmol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma. Both authors contributed equally to this work. The study of the investigational new drug was approved and it was provided by Sanofi-Synthelabo Inc., Budapest, Hungary. This work was supported by the grant of the Health Science Council of the Ministry of Health, Republic of Hungary (ETT) No. 225.     

Expressions of IL-17 and TNF-α in patients with Hashimoto’s disease combined with thyroid cancer before and after surgery and their relationship with prognosis

Clinical and Translational Oncology - This study aimed to investigate expressions and clinical significance of IL-17 and TNF-α after surgery in patients with Hashimoto’s disease (HD)...     

Being a teenager and cancer patient: What do adolescents and young adults with cancer find valuable and challenging with their friends and cancer peers?

Abstract

Purpose: This study examined Adolescent and Young Adult (AYA) cancer patients’ experiences with friends and cancer friends (peers) throughout their cancer journey.

Research approach: Qualitative, thematic analysis.

Participants: Twelve AYA diagnosed with cancer, treated within the past five years.

Methodological approach: Individual semi-structured interviews, focusing on friend and peer experiences pre-/post-diagnosis, during and after treatment.

Findings: Overarching themes of ‘valued’ vs. ‘challenging’ aspects with friends and peers.

Interpretation: Friend and peer relationships were both valuable, but in different ways. Friends provided general support and helped AYA feel like a normal teenager, while peers provided targeted support and helped AYA feel like a normal teenager with cancer. Peers had an intimate understanding of cancer, whereas poor understanding by friends led to further challenges such as avoidance and being dismissive. Peer relations were notably challenged by a premature confrontation with mortality. Friendships evolved and changed throughout the cancer journey.     

Sarcopenia and obesity among patients with soft tissue sarcoma – Association with clinicopathologic characteristics,complications and oncologic outcome: A systematic review and meta-analysis

Background and aimsSarcopenia and obesity may be associated with negative outcomes in many cancers, but their prevalence and impact in modern regimens for soft-tissue sarcoma (STS) have not been systematically studied. This study summarises and critically evaluates the current evidence-based literature on body mass index (BMI) and body composition among patients with STS, with respect to clinical and pathologic characteristics, treatment-associated morbidity and oncologic outcome.MethodsA systematic literature search of the PubMed, Embase and Cochrane databases was performed. Meta-analysis of the relationship between BMI, body composition and pathologic characteristics, operative morbidity and oncologic outcome was undertaken using RevMan v.5.4 using fixed or random effects methods as appropriate.Results14 studies including 3598 patients met inclusion criteria. Ten studies reported on BMI, two on CT and two on PET-CT assessment of body composition. BMI ranged from 14.6 to 63.7 kg/m², with obesity in 18%–39% of patients. Although some studies demonstrated larger tumours among patients with obesity, this was not significant on meta-analysis (P = 0.31, I² = 99%). There was no significant difference in tumour grade or histologic type according to BMI. Postoperatively, obesity was associated with increased risk of overall morbidity (odds ratio (OR) 2.03 [95% CI 1.41–2.92], P = 0.0001, I² = 22%), and wound morbidity (OR 1.32 [95% CI 1.02–1.71], P = 0.03, I² = 0%). Similar effects were observed in studies of visceral adiposity. No differences in functional outcomes were observed. There was a trend towards reduced local recurrence among patients with obesity (HR 0.64 [95% CI 0.38–1.08], P = 0.10, I² = 0%), but no difference in distant metastasis (HR 1.00 [95% CI 0.76–1.30], P = 0.98, I² = 0%) or overall survival (HR 0.98 [95% CI 0.43–2.22], P = 0.95, I² = 64%). Various measures of sarcopenia were associated with poorer survival outcomes.ConclusionWhile obesity is associated with increased postoperative morbidity, it had no significant association with long-term oncologic outcomes. Sarcopenia may be associated with a poorer long-term prognosis. A greater understanding of the impact of nutritional status on disease characteristics and treatment outcomes is essential to facilitate improvements in clinical care for patients with STS.     

Phosphatase of Regenerating Liver and Its Association with Tumors

Protein kinases and protein phosphatases play key roles in regulating functions of diverse proteins which control numerous     

Expression of Cyclin E and Its Relationship with the Prognosis of Patients with Breast Cancer

Objective： To investigate the expression of cyclin E in breast cancer tissues and its relationship with prognosis of the patients with breast cancer. Methods： The expression of cyclin E, HER-2/neu, nm23-H1 and actin was detected in 80 breast cancer tissues and 18 benign breast tumor tissues by immunohistochemical methods. The relationship between cyclin E and the remaining genes or the clinical data of the patients with breast cancer was analyzed. Results： The over expression rate of cyclin E in malignant tissues was obviously higher than that in benign tumor tissues （P〈0.01）. The over expression of cyclin E in later stage of disease was higher than that in early stage of disease （P〈0.05）. The expression of cyclin E in ER positive tissues was lower than that in ER negative tissues （P〈0.05）. The expression of cyclin E in PR positive tissues and PR negative tissues had no significant difference （P〉0.05）. The expression of cyclin E in HER-2/neu positive tissues was higher than that in HER-2/neu negative tissues （P〈0.05）. And the expression of cyclin E in ER, PR and HER-2/neu all positive tissues was much higher （P〈0.01）. There was no significant difference in the expression of cyclin E between nm23-H1 positive tissues and nm23-H1 negative tissues （P〉0.05）. The expression of cyclin E in actin positive and continuous distribution tissues was lower than that in actin negative or discontinuous distribution tissues （P〈0.05）. Conclusion： The expression of cyclin E has a strong correlation to the prognosis of the patients with breast cancer.     

Colic and rectal tumors with peritoneal metastases treated with cytoreductive surgery and HIPEC: One homogeneous condition or two different diseases? A systematic review and meta-analysis

Colorectal cancer (CRC) peritoneal metastasis (PM) is one of the most important cause of cancer-related death in world. CRC PM is considered as a homogeneous disease without differentiating colonic or rectal origin. Aim of this study is to analyze survival of patients treated with cytoreductive surgery and HIPEC, according to the origin of PM.Literature search was performed to identify relevant articles. All meta-analysis were performed using mean difference and log of HR, when appropriate. The I² statistic was used to determine the heterogeneity of included studies.Out of 349 selected records, 9 articles (1308 patients, 1153 colon PM and 155 rectal PM) have been included. OS and DFS is higher in patients affected by colon PM (OS mean difference: 24,49 months [95% CI: 14,70-34,28 months, p < 0,000001]; DFS mean difference: 7,75 months [95% CI: 1,37-14,13 months, p: 0,02]) and pooled Hazard Ratio for disease-related death in rectal PM is 1.62 [95% CI: 1,01-2,59, p: 0,05] compared to colon PM). Heterogeneity among selected studies is high in two subgroups and low in one (OS subgroup A I²: 98%, p < 0,000001; DFS subgroup I²: 91%, p < 0,000001; OS subgroup B I²: 25%, p: 0,26).Our analysis, with all the limitations related to included studies, suggests that peritoneal metastasis of rectal tumors treated with CRS and HIPEC have a worst prognosis of colon tumors PM. Larger studies are required to confirm those results and therefore we invite all Authors in considering also tumor localization when reporting data on CRC peritoneal metastasis treatment.     

Combination chemotherapy with docetaxel and cisplatin for locally advanced?and metastatic gastric cancer

Background:Poor treatment results obtained with palliativechemotherapy for advanced gastric cancer indicate the need for new effectiveand well-tolerated regimens. Patients and methods:Forty-three patients with locally advancedor metastatic gastric cancer were enrolled in a phase II study to evaluate theefficacy and safety of combination chemotherapy with doxetacel 75mg/m² and cisplatin 75 mg/m² given every threeweeks. Results:Thirty-nine patients were evaluable for response. Fourachieved a complete response and twelve a partial response, for an overallresponse rate of 37.2% (16 of 43 patients; 95% confidenceinterval (CI): 22.98–53.72). Median time to progression was 6.1 monthsand median overall survival 10.4 months. Forty-two percent of all patientswere still alive at one year and twelve percent at two years. The majortoxicity was leukopenia which reached grade 3–4 in 18.6%(n = 8) of the patients. However, no febrile neutropeniaoccurred. Non-haematological toxicities were usually mild to moderate. Grade3 toxicities included diarrhea (9% of the patients), nausea andvomiting (7%), and alopecia (7%). Severe ototoxicity with orwithout peripheral neuropathy developed after completion of chemotherapy intwo patients. Conclusions:These results suggest that the combination ofdocetaxel and cisplatin has moderate toxicity and is an effective regimen forthe treatment of advanced gastric cancer, both with regard to response rateand survival.     

Children with DIPG and high-grade glioma treated with temozolomide,irinotecan, and bevacizumab: the Seattle Children’s Hospital experience

Journal of Neuro-Oncology - Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases...     

Myelodysplastic syndrome with complex karyotypic abnormality in a patient with Waldenström's macroglobulinemia after sequential treatment with chlorambucil and fludarabine

A therapy-related myelodysplastic syndrome (t-MDS) during the course of Waldenstr?m's macroglobulinemia (WM) has been observed in rare patients. In most of them, the condition developed after treatment with alkylating agents. We experienced a 65-year-old male patient who was diagnosed as WM. He was treated with intermittent oral chlorambucil for 12 months and three cycles of fludarabine, and complete response was achieved after fludarabine treatment. During routine outpatient follow-up, severe anemia occurred. His bone marrow aspirate showed dysplastic hemopoiesis with ringed sideroblasts and siderocytes, which is consistent with MDS (refractory anemia with ringed sideroblasts). Cytogenetic analysis showed complex chromosomal abnormalities including 5q deletion, 12p deletion and monosomy 18. When decision is made to treat WM with chlorambucil and/or fludarabine, a potential risk for t-MDS or therapy-related acute myeloid leukemia should be considered and a close hematologic monitoring is needed.     

Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients?with?hepatic metastases from colorectal cancer

Background:To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of oxaliplatin administered as hepatic arterial infusion. Patients and methods:Patients with isolated hepatic metastases from colorectal cancer were treated every three weeks with increasing doses of oxaliplatin (4 hours; starting dose 25 mg/m², escalation in steps of 25 mg/m²) in combination with folinic acid (1 hour, 200 mg/m²) and 5-fluorouracil (2 hour, 600 mg/m²). Results:Twenty-one patients (median age, 61 years) have been entered all of whom are fully evaluable. The DLT has been observed at dose level 6, i.e., at 150 mg/m²/cycle and consisted of leucopenia, obliteration of the hepatic artery, and acute pancreatitis. Overall, toxicity mainly consisted of nausea/vomiting (16 of 21 patients), anemia (16 of 21), upper abdominal pain (15 of 21), sensory neuropathy (10 of 21), diarrhea (9 of 21), and thrombocytopenia (9 of 21). The mean PK parameters were: terminal half-life of ultrafiltrable platin, 17.75 ± 9.29 hours; renal elimination, 48.7% ± 14.1% of the applied dose; renal clearance 135.55 ± 45.32 ml/min. The mean area under the plasma-concentration curve (AUC) increased linearly from 3.22 ± 0.61 µg · h/ml to 18.45 ± 8.90 µg · h/ml through the first five dose levels (P = 0.0004). Ten of eighteen evaluable patients achieved a complete or partial response (59%). Conclusions:The recommended dose for phase II studies is 125 mg/m² oxaliplatin.     

Intravenous leiomyomatosis with intracardiac extension – A review of diagnosis and management with an illustrative case

Intravenous leiomyomatosis with intracardiac extension is an uncommon pathologic progression of uterine leiomyomata. It is a histologically benign condition, however due to interfence with right sided cardiac function patients may present with marked cardiovascular compromise and present a diagnostic dilemma to clinicians who are unfamiliar with this condition. Given the rarity of this condition, experience in individual institutions is usually limited to a few cases. We present an illustrative case and provide a review of the clinical presentation, preoperative assessment, operative approach, pathology and postoperative issues. The importance of a multidisciplinary approach to diagnosis and management is highlighted. Operative management aims to completely resect all tumour in the safest manner for the patient, most commonly via single or two stage operation. Where complete resection is achieved, recurrence appears to be a rare event.     

Are Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios Associated with Endometrial Precancerous and Cancerous Lesions in Patients with Abnormal Uterine Bleeding?

Background: An easy, reproducible and simple marker is needed to estimate phase of endometrial pathologiclesions such as hyperplasia and endometrial cancer and distinguish from pathologically normal results. Wehere aimed to clarify associations among neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio(PLR), endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. Materials and Methods:Patients (n=161) who were admitted with abnormal uterine bleeding and the presence of endometrial cells oncervical cytology or thick endometrium were investigated. The study constituted of three groups accordingto pathologic diagnosis. Group 1 included endometrial precancerous lesions like hyperplasia (n=63), group 2included endometrial cancerous lesions (n=38) and group 3 was a pathologically normal group (n=60). Bloodsamples were obtained just before the curettage procedure and the NLR was defined as the absolute neutrophilcount divided by the absolute lymphocyte count; similarly, PLR was defined as the absolute platelet count dividedby the absolute lymphocyte count. Results: The white blood cell count was significantly higher in patients withcancer than in those with hyperplasia (p=0.005). The platelet count and neutrophil to lymphocyte ratio weresignificantly higher in patients with cancer than in control patients, but there was significantly no differencebetween patients with hyperplasia and other groups (p=0.001 and p=0.025 respectively). PLR was significantlylower in control subjects than in other groups (p<0.001), but there was no significant difference between patientswith hyperplasia and those with cancer. Conclusions: PLR was significantly lower in control subjects than inother groups. Thus both hyperplasia and cancer may be differentiated from pathologically normal patients byusing PLR. White blood cell count was significantly higher in patients with cancer than in those with hyperplasiaand pathologically normal patients. Therefore white blood cell count may be used for discriminate hyperplasia tocancer. By using multiple inflammation parameters, discrimination may be possible among endometrial cancer,endometrial precancerous lesions and pathologically normal patients.     

Correlation of prothrombin time with clinicopathological features and prognosis of patients with osteosarcoma北大核心CSCD

Objective: To investigate the correlation of prothrombin time (PT) with clinicopathological features and prognosis of the patients with osteosarcoma. Methods: The activated partial thromboplastin time (APTT), PT, fibrinogen (FIB) and D-dimer in peripheral blood of 111 patients with osteosarcoma and 35 concurrent healthy volunteers (as the control) from May 2011 to May 2018 were tested. The correlation of PT with clinicopathological features and prognosis of the patients with osteosarcoma was analyzed. Results: The median survival time of 111 patients with osteosarcoma was 25 months, and the one-and two-year survival rates were 76.6% and 51.4%, respectively. The levels of D-dimer and FIB in the patients with osteosarcoma were higher than those in the control group (both P < 0.01), and the PT was shorter than that in the control group (P < 0.01), while the APTT was not statistical different between these two groups (P > 0.05). The PT was longer in the patients with osteosarcoma younger than 20 years old (P = 0.002), while PT had no correlation with gender, tumor size, clinical stage, tumor location and metastatic status (all P> 0.05). The overall survival time of the patients with osteosarcoma in PT ≥ 10.4 s group was shorter than that in PT < 10.4 s group (P = 0.024), the progression-free survival time of the patients with osteosarcoma had no significant difference between these two groups (P= 0.594). The overall survival time and progression-free survival time of the patients with osteosarcoma in metastasis group were shorter than those in non-metastasis group (both P< 0.001). The overall survival time (P= 0.004) and progression-free survival time (P= 0.013) of the patients with osteosarcoma in stage I / II group were longer than those in stage EI/IV group. The clinical stage, PT and metastasis status were related with the prognosis of patients with osteosarcoma (all P< 0.05). The PT and metastasis status were independent predictive factors for the prognosis of patients with osteosarcoma (both P < 0.05). Conclusion: The changes of PT may provide a reference for monitoring the condition and prognosis of patients with osteosarcoma. © 2019 by TUMOR. All rights reserved.     

Bortezomib induces apoptosis and growth suppression in human medulloblastoma cells, associated with inhibition of AKT and NF-ĸB signaling, and synergizes with an ERK inhibitor

Medulloblastoma is the most common brain tumor in children. Here, we report that bortezomib, a proteasome inhibitor, induced apoptosis and inhibited cell proliferation in two established cell lines and a primary culture of human medulloblastomas. Bortezomib increased the release of cytochrome c to cytosol and activated caspase-9 and caspase-3, resulting in cleavage of PARP. Caspase inhibitor (Z-VAD-FMK) could rescue medulloblastoma cells from the cytotoxicity of bortezomib. Phosphorylation of AKT and its upstream regulator mTOR were reduced by bortezomib treatment in medulloblastoma cells. Bortezomib increased the expression of Bad and Bak, pro-apoptotic proteins, and p21Cip1 and p27Kip1, negative regulators of cell cycle progression, which are associated with the growth suppression and induction of apoptosis in these tumor cells. Bortezomib also increased the accumulation of phosphorylated IĸBα, and decreased nuclear translocation of NF-ĸB. Thus, NF-ĸB signaling and activation of its downstream targets are suppressed. Moreover, ERK inhibitors or downregulating ERK with ERK siRNA synergized with bortezomib on anticancer effects in medulloblastoma cells. Bortezomib also inhibited the growth of human medulloblastoma cells in a mouse xenograft model. These findings suggest that proteasome inhibitors are potentially promising drugs for treatment of pediatric medulloblastomas.     

Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery?

BACKGROUND: Contemporary therapy for osteosarcoma is comprised of initial treatment with chemotherapy and surgical extirpation of the primary tumor in the affected bone. In view of the major advances forged by chemotherapy in the treatment of the primary tumor, an attempt was made to destroy the tumor exclusively with this therapeutic modality and abrogate surgery. METHODS: Thirty-one consecutive patients were treated. All had localized disease (absence of metastases) at the time of diagnosis. Initial treatment with chemotherapy was comprised of high-dose methotrexate and leucovorin rescue (MTX-LF) in 3 patients and intraarterial cisplatin in 28 patients. Clinical, radiologic, angiographic, radionuclide, and histologic investigations were utilized to assess the efficacy of treatment. After a response at 3 months, entry into the study was permitted and treatment was maintained for a total of 18-21 months with a combination of agents comprised of MTX-LF, intraarterial cisplatin, and doxorubicin. Patients were monitored closely for disease recurrence with the investigations outlined earlier. Two informed consents were required: one at the time of diagnosis and another at 3 months after the initial response had been attained. RESULTS: Only 3 of 31 patients were cured with the administration of chemotherapy alone. Local recurrence and pulmonary metastases were not reported to develop in these 3 patients during a follow-up period of 204+ to 225+ months. Four other patients also possibly were cured with chemotherapy alone. At their request, several months after the cessation of chemotherapy, they underwent surgical extirpation of the tumor. No evidence of viable tumor was found. These patients remained free of disease for 192+ to 216+ months. Thus, only seven patients did not develop local recurrence and/or pulmonary metastases. Among the remaining 24 patients, 9 developed local recurrences without pulmonary metastases 14-74 months (median, 30 months) after the initial response. Eight of the nine patients were rendered tumor free by extirpation of the local recurrence. Two of these eight patients subsequently died, one of the acquired immunodeficiency syndrome (AIDS) and the other of varicella septicemia. The ninth patient refused amputation and died of metabolic complications. Three other patients developed local recurrences 20-69 months and pulmonary metastases 10-98 months after achievement of the initial response. These patients were rendered tumor free by extirpation of the local recurrence and metastasectomy. One of these patients also later died of AIDS. In the remaining 12 patients, local recurrences developed 5-29 months (median, 14 months) after the initial response was achieved. The patients also developed pulmonary metastases 11-60 months after the initial response. In eight patients the local recurrences were extirpated and metastasectomy was performed; however, these patients later died of recurrent pulmonary metastases. The remaining four patients refused to undergo extirpation of the local recurrence. The pulmonary metastases were not resected. They failed to respond to alternate therapy. Thus, the tumor-free survival rate was 23% (7 of 31 patients): 3 patients who were treated with chemotherapy only and 4 patients who were treated with chemotherapy plus surgery. The overall survival rate (patients who remained free of disease and those who underwent resection for local recurrence and metastasectomy) was 48% (15 of 31 patients). Prior to the deaths from AIDS and varicella septicemia, the overall survival was 58% (18 of 31 patients). CONCLUSIONS: Utilizing the regimen employed in the current study, only 3 of 31 patients with osteosarcoma (10%) were cured exclusively with chemotherapy. Four additional patients who underwent extirpation of the primary tumor without disease recurrence and in whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" sin whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" strategies, the results of the current study do not justify the adoption of current forms of chemotherapy as exclusive treatments for osteosarcoma.