High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation as Frontline Therapy for Intermediate/High-risk Diffuse Large B Cell Lymphoma

The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.

Work-up and management of a high-risk patient with primary central nervous system lymphoma

Primary central nervous system lymphoma(PCNSL) is a rare disorder that, in 95% of cases, represents diffuse large B-cell lymphoma. As such, making an accurate diagnosis is important. At present, stereotactic-guided biopsy is a recognized method of choice for tissue analysis. However, the diagnostic work-up for high-risk patients is determined by their performance status. Here,we report a case of PCNSL in a high-risk patient, for whom diagnosis was established by cerebrospinal fluid cytology and flow cytometry, which significantly shortened a diagnostic work-up period and allowed for the immediate treatment of the patient.

Multiple therapeutic and preventive effects of 3,3'-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross.These vegetables are an abundant source of dietary phytochemicals,including glucosinolates and their hydrolysis products such as indole-3-carbinol（I3C） and 3,3＇-diindolylmethane（DIM）.By 2013,the total number of natural glucosinolates that have been documented is estimated to be 132.Recently,cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer,antiviral infections,human sex hormone regulation,and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia（HGPIN）.DIM is a hydrolysis product of glucosinolates and has been used in various trials.This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN.

Bugbee flexible electrocautery facilitates choledochoscopic biopsy,fulguration,and debulking of a high grade intraductal papillary neoplasm of the bile duct

To the Editor:Intraductal papillary neoplasm of the bile duct(IPNB)may occur in the setting of primary sclerosing cholangitis,choledochal cysts or hepatolithiasis[1].The entity may be a precursor of cancer or intrahepatic cholangiocarcinoma.Invasive carcinoma,tubular or mucinous adenocarcinoma is present in approximately 40%-80%of IPNBs[1–3].IPNB is frequently found in the resection margins of patients undergoing hepatectomy for cholangiocarcinoma[4].

Advancement in high dose therapy and autologous stem cell rescue in lymphoma

A lthough advanced stage aggressive non-Hodgkin'slymphomas and Hodgkin's disease are thought to be che-motherapy-responsive cancers, a considerable number of patients either relapse or never attain a remission. High-dose therapy(HDT) followed by autologous stem cell transplantation(ASCT) is often the only possibility of cure for most of these patients. However, many controversial issues still remain with respect to HDT/ASCT for lymphomas, including its role for, the optimal timing of transplantation, the best conditioning regimen and the potential use of localized radiotherapy or immunologic methods to decrease post-transplant recurrence. Recently, mainly due to the unavailability of carmustine, several novel conditioning protocols have been clinically developed, with the aim of improving the overall outcome by enhancing the anti-lymphoma effect and, at the same time, by reducing short and long-term toxicity. Furthermore, the better safety profiles of novel approaches would definitively allow patients aged more than 65-70 years to benefit from this therapeutic option. In this review, we will briefly discuss the most relevant and recent data available regarding HDT/ASCT in lymphomas.

Temozolomide resistance in high grade gliomas

High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.

Low Dose Total Body Irradiation for Relapsed Low Grade Non-Hodgkin’s Lymphoma: Experience of National Cancer Institute, Cairo

Background and Purpose: The relapsed low grade non-Hodgkin’s lymphoma (LG-NHL) is currently?incurable disease and the optimal treatment regimen has not determined yet. Low dose total body irradiation (LTBI) provides an alternative mechanism of action against cancer cells rather than direct cell kill. The mode of action of LTBI is immune-modulatory effect, induction of apoptosis and?hypersensitivity to low radiation doses. The aim of our study is to evaluate the effect of LTBI on relapsed?LG-NHL and reporting our experience at National Cancer Institute, Cairo (NCI, Cairo). Material and Methods: Fifty eight patients with relapsed LG-NHL and received LTBI studied retrospectively.?LTBI dose was 1.6 Gy/8 fractions divided on 2 courses;each course 4 fractions treated over 4 days with 2 weeks rest between the 2 courses. Results: The median age is 54 years;65% of the patients are men. Forty (69%) patients had performance status of 2 or more. Twenty seven patients were stage II/III and 31 patients (53%) had stage IV disease. Twenty six (45%) patients had bulky disease more than 10 cm and 22 (38%) patients had B symptoms at the time of relapse. The?extranodal disease was present in 17 patients (29%) and 78% of the patients received?>3 regimens of chemotherapy before referral to LTBI. Twenty three patients received IFRT (mean dose 32 ± 4 Gy) to initially bulky sites after LTBI. Fourteen patients (24%) achieved complete remission (CR) while 45%, 21% and 10% had partial remission (PR), stable disease (SD) and progressive disease (PD) respectively. The median PFS duration was 14 months and the median OS duration?was 39 months. Stage VI,?>3 regimen of chemotherapy and bad response to LTBI (SD) affected?progression duration adversely (0.03, 0.05 and 0.01 respectively). The response to LTBI is the only factor affected the OS duration significantly. The 3-year PFS was 19% ± 9%, and 3-year OS was 45% ± 8%. Stage IV was the only factor affected the 3-year PFS significantly with p value 0.03. The hematological toxicity was the main side effect of LTBI. Eleven patients developed G3/4 anemia while 8 patients only developed G3/4 thrombocytopenia and 13 patients developed G3/4 leucopenia. Conclusion: The use of LTBI in patients with relapsed low grade NHL is a feasible, effective and tolerable treatment that is worthy of testing in a future with chemotherapy and Rituximab maintenance.

HIGH DOSE CHEMORADIOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE TREATMENT OF ADVANCED HODGKIN's LYMPHOMA:A REPORT OF 11 CASES

Objective: High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the important salvage treatments for the Hodgkin抯 Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results: The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1-80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one of them is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability of 6-year PFS and OS is 55.68% and 100% respectively. The dominating transplant- related toxicity was bone marrow suppression in grades IV. No obvious cardiac, hepatic, and nephritic toxicity was found. No transplant related mortality. Conclusion: HDT combined with ASCT is a method worthwhile to further study for the treatment of the patients with advanced or relapsed Hodgkin抯 Lymphoma with poor prognostic factors.

A New Sound Alloy for High Grade Wind Instruments

A new sound alloy, abbreviated to S, has been developed by the General Research Institutefor Non-ferrous Metals, Beijing. The alloy is very suitable for making trumpets, trombones, tenorhorns, saxaphones and other kinds of wind instruments. Beijing Wind Instrument Factory, which is the largest one in China, has used Salloy formanufacturing 5200 type trompets, the sound performance of which has been examined with fre-quency analysis and experimented by famous musical experts. The results show that the 5200 typetrumpets made of Salloy have excellent quality, accurate intonation and ease of response at

Low-Dose Involved-Field Radiotherapy in Relapsed Low-Grade Non-Hodgkin's Lymphoma in Elderly Patients (Mansoura University Experience)

Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients and Methods: Forty-four patients were included. Patients were treated with a total dose of 4 Gy (2 × 2 Gy) using 6 - 15 Mv photon or electron beam. Results: most patients were above age of 60 years (59%) with male predominance. Follicular lymphoma was the most common pathological type;bulky disease (>5 cm) was presented in 61.4%. Patients who received only 2 regimens were 63.7% and 31.8% had >2 involved sites. No treatment related toxicity was observed. The overall response rate was 88.7%;complete response was reached in 59.1% and stable disease in 6.8%, progressive disease in 4.5%. Median time to local progression was 33 months (95% CI 23.70 - 42.29);2-year local progression free survival was 78%. Response rate was found to be dependent on age, number of involved sites and lymph node size but independent on sex, pathological type, number of prior regimens, LDH level and time since diagnosis. Conclusion: Short-course-low dose palliative radiotherapy (2 × 2 Gy) affords an attractive option for treatment of relapsed low-grade non-Hodgkin’s lymphoma due to high response rates. However, these results had to be confirmed in a larger number of patients.

High Grade Muscle-Invasive Urinary Bladder Cancer in A 36 Year Old Male Patient:A Case Report&Review of Literature

We are reporting a case of urothelial bladder cancer in a 36 year old male patient with no history or exposure to any risk factors.The incidence of urothelial bladder cancer is very low in young individuals i.e.below 40 years of age with reported rate of incidence around 0.1-0.4%.Most of the times,these young individuals present with non-muscle invasive bladder cancer with low grade and low stage.As the age increases,the incidence of high grade bladder cancer increases along with it.The index case presented with high grade muscle invasive bladder cancer at the time of diagnosis without any known risk factors.The 5-year survival of urothelial bladder cancer is better in young patients(93.8%)as compared to older people(85.1%).Cigarette smoking is responsible for development of bladder cancer in majority of patients followed by exposure to occupational carcinogens.Role of genetic alterations in development of bladder cancer is still under research and process of urothelial bladder carcinogenesis is unanswered in young individuals.

360° fusion for realignment of high grade cervical kyphosis by one step surgery: Case report

Surgical treatment for cervical kyphotic deformity is still controversial. Circumferential approach has been well described in the literature but long terms outcomes are not well reported. Important to decide the correct treatment option is the preoperative radiological exams to value the type of deformity(flexible or fixed). We report the case of a 67-year-old woman affected by a severe cervical kyphotic deformity who underwent combined anterior/posterior surgical approach, getting a good reduction of the deformity and an optimal stability in a long term follow up.

Barrett's esophagus with high grade dysplasia is associated with non-esophageal cancer

AIM To study factors associated with esophageal and nonesophageal cancer morbidity among Barrett's esophagus(BE) patients. METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related(defined as esophagus and cardia) and non-BE related cancers(all other cancers). Cancer incidence and all-causemortality were compared between patients with highgrade dysplasia(HGD) and with low-grade or no dysplasia(non-HGD) using Kaplan-Meier curves and cox regression models.RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75(19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven(1.8%) and 18(4.7%) patients had BE and non-BE incident cancers, respectively. Twelve(3.1%) patients had HGD as worst histologic result. Two(16.7%) and 16(4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference(P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.

Synthesis of high grade octahedron diamond through epitaxial growth

The work was based on the relationship between the crystal structure and parameters of diamonds in the synthetic process, in which Ni Mn C powder catalyst was used. At first, the diamond crystals nucleated in a cubic octahedron morphology through controlling such synthetic parameters as temperature and pressure in a parameter region where cubic octahedron ctystals can be obtained. Then the diamond nuclei grew epitaxially into crystals with a perfect octahedron morphology through increasing the synthesis temperature and decreasing the synthesis pressure in a parameter region where octahedron crystals can be obtained.

Primary Endometrial High Grade Neuroendocrine Carcinoma: A Case Report with Cytological, Histopathological and Immunohistochemical Features

An 84-year-old woman suffered from post-menopausal genital bleeding for 3 months. Based on the endometrial cytological findings (suggestive of high grade neuroendocrine carcinoma) showing that there were rosette-like and cord-like structures consisting of small rounded tumor cells with oval nuclei and scanty cytoplasm, radical hysterectomy was performed. Histopathological and immunohistochemical examinations on the operated specimens revealed primary high grade neuroendocrine carcinoma of the endometrium. Despite the extensive treatment against the malignancy, the patient died due to widespread metastases after 5 months after the surgery and autopsied.

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.

THE PRELIMINARY RESULTS OF TREATMENT OFADVANCED AND RECURRENT MALIGNANT LYMPHOMA BY BEAC REGIMEN SUPPORTED WITH AUTOLOGOUS HEMATOPOIETIC STEM CELLS TRANSPLANTATION

Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment for the chemo-sensitive lymphoma. The purposes of this study was to evaluate the efficacy and tolerance of preparative regimen BEAC and hematopoietic reconsti- tution after high dose chemotherapy in Chinese patients with advanced and recurrent lymphoma. Methods: After confirmed complete or partial remission from conventional chemotherapy, 24 patients with advanced or recurrent lymphoma including 1 recurrent HD and 23 NHL, 16 male and 8 female with median age of 29 (13-50) years, were enrolled into this study and treated by BEAC regimen (CTX 3600-4000 mg/m2, VP-16 1200 mg/m2. BCNU 300 mg/m2 and Ara-C 1500-2000 mg/m2). 3 patients were supported by ABMT and 21 by APBSCT. Mobilization regimen for APBSCT was CTX 3500 mg/m2 + G-CSF 3.5-5 mg/kg + Dexamethasone 10 mg. Autologous hematopoietic stem cells was re-infused 24-48 h after completion of high dose chemotherapy. Results: MNC 1.3 (1.0-1.7) 108/kg and MNC 1.8 (1.0-4.4) 108, CFU-GM 5.1 (1.9-9.6) 105/kg plus CD34 + cells 2.9 (1.9-8.7) 106/kg were re-infused in the ABMT group and APBSCT group respectively. All patients obtained prompt and sustained hematopoietic reconstitution. ANC 0.5 109/L and Pt 2.0 109/L were at day 9 (6-17) and day 10 (0-31) respectively. 16 patients were alive with median 21 (2-69) months follow-up till end of May, 2001. 1, 2 and 3 years survival rate were 60.5%, 50.1% and 50.1%, respectively. Non-hematologic toxicity was mild and tolerable. Conclusions: High dose chemotherapy supported by AHSCT in the treatment of previously-untreated poor- prognostic and recurrent lymphoma was a safe and effective modality. Further investigation was warranted.

Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation

Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （NHL）. However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose （FDG） positron emission tomography （PET）/computed tomography （CT） has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods： A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria （5-point scale） were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic （ROC） curve. Results： In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival （PFS） and overall survival （OS）. Patients with negative pre-ASCT PET result demonstrated significantly better PFS （84.2% vs. 54.2%） and OS （89.2% vs. 63.6%） than patients with positive pre-ASCT PET result. PFS （91.6% vs. 25.3%） and OS （96.5% vs. 36.8%） were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions： Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.

The Impact of Human Immunodeficiency Virus Infection (HIV) on Lymphoma in South Africa

Human immunodeficiency virus (HIV) infection is endemic in South Africa. Non-Hodgkin lymphoma (NHL) occurs with increased frequency in HIV seropositive individuals. The increase in NHL has been more marked in the last decade, with HIV being the major contributor to this increase. More than 70% of the adult NHL patients at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, Johannesburg, are HIV seropositive. In addition, HIV has impacted on the clinical presentation—being more aggressive and atypical. Histologically, HIV-NHL typically manifests as B-cell, high grade lymphomas, including diffuse large B-cell lymphoma (DLBCL);Burkitt lymphoma (BL);B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL and plasmablastic lymphoma. The latter two entities, which were previously rare or unknown, have gained prominence in the last decade, occurring primarily in HIV seropositive individuals. HIV-NHL, being associated with all these adverse prognostic factors results in a poorer overall survival.