A 20-year experience on malignant lymphomas in patients aged 70 and older at a single institute

We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.     

Rituximab: perspective on single agent experience, and future directions in combination trials

Monoclonal antibody (MAb) CC49 reacts with a pancarcinoma antigen, tumor associated glycoprotein (TAG)-72. To circumvent human anti-murine antibody (HAMA) responses in patients, we earlier developed a humanized CC49 (HuCC49) by grafting the complementarity-determining regions (CDRs) of MAb CC49 onto variable light (VL) and variable heavy (VH) frameworks of the human MAbs LEN and 21/28'CL, respectively. With the aim of minimizing its immunogenicity further, we have now generated a variant HuCC49 MAb by grafting the specificity-determining residues (SDRs) of MAb CC49 onto the frameworks of the human MAbs. Based on the evaluation of its binding affinity for TAG-72 and its reactivity with anti-idiotypic antibodies present in sera from patients who have been treated with murine CC49, this variant retains its antigen-binding activity and shows minimal reactivity with anti-idiotypic antibodies in patients' sera. Development of this variant, which is a potentially useful clinical reagent for diagnosis and therapy of human carcinomas, demonstrates that for humanization of a xenogeneic antibody grafting of the potential SDRs should be sufficient to retain its antigen-binding properties.     

Imatinib mesylate therapy in advanced gastrointestinal stromal tumors: experience from a single institute

Gastrointestinal stromal tumors (GIST) are rare soft tissue sarcomas arising primarily from mesenchymal tissue in the gastrointestinal tract and abdomen. Since there is no effective treatment in the advanced stages, the outcome is poor in such patients. Recently, imatinib mesylate, a selective tyrosine kinase inhibitor, has shown a promising effect in GIST. Hence, we report our experience on the management of advanced GIST with imatinib therapy. A total of 14 patients were enrolled in this study, including 10 males and four females (median age, 51 years). The results showed that the small intestine was the most frequent site of primary lesion, while the liver was the most frequently metastasized organ. Most of the patients experienced tolerable side effects with imatinib therapy, including edema of periorbital area and/or legs and abdominal pain. Only two mortalities were noted during follow-up. The patients clinically benefited from imatinib therapy, with one patient having a complete response, three having a partial response, and seven having stable disease. The results demonstrate promising effects of imatinib in advanced GIST.     

Radiation therapy in indolent primary cutaneous B cell lymphoma: a single institute experience

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p?=?0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p?=?0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.     

Clinical manifestations and pathogenesis of cutaneous lymphomas: current status and future directions

The primary cutaneous lymphomas are a heterogeneous group of T‐, Natural Killer‐ and B‐ cell neoplasms with a wide range of clinical and pathological presentations, and with very different prognoses compared to systemic lymphomas. Recent studies have shown that the skin microenvironment, which is composed of various immune cell subsets as well as their spatial distribution and T‐cell interactions through different chemokines and cytokines, has an important role in the development and pathogenesis of cutaneous lymphomas and has assisted in the development of novel and more effective immunotherapies. The following review will focus on the major subtypes of primary cutaneous lymphomas, including the clinical and histological patterns, molecular hallmarks, and current and future treatment strategies.     

Palliative radiation therapy for hemorrhage of unresectable gastric cancer: a single institute experience

Purpose  To clarify the toxicity of palliative radiotherapy (RT) and its efficacy against bleeding of unresectable gastric cancer. Methods  Clinical data of 19 patients received palliative RT for bleeding from unresectable gastric cancer were reviewed. The median total dose and dose per fraction were 40 Gy (range 2–50 Gy) and 2.5 Gy (range 1.8–3 Gy). Results  The treatment success rate was 68.4%. By using a tumor alpha/beta ratio of 10, biological effective dose of 50 Gy₁₀ or more was significantly correlated with treatment success (P = 0.040). The median event-free survival was 1.5 months after RT and the median overall survival from starting RT was 3.4 months. Grade 3 nausea and anorexia were recorded in 1 and 3 patients, respectively. Conclusion   Palliative RT was effective for hemostasis in patients with gastric cancer bleeding with minor adverse events.     

Clinicopathological analysis of 598 malignant lymphomas in Taiwan: seven-year experience in a single institution

The clinicopathological characteristics of malignant lymphomas vary according to geography. The purpose of this study is to determine the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan. Archival tissue from 598 malignant lymphomas during the period of 1995-2002 was retrieved. They were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. There were 330 males and 268 females. The median age at onset of disease was 56 years for B-cell lymphoma (BCL), 50 years for T/NK-cell lymphoma (TCL), and 26 years for Hodgkin's lymphoma (HL). BCL accounted for 80.6%, TCL for 12.4%, and HL for 7%. The major subtypes of non-HL were diffuse large B-cell lymphoma, follicular lymphoma, plasma cell myeloma, marginal zone lymphoma of mucosa-associated lymphoid tissue type, mantle cell lymphoma, unspecified peripheral TCL, and nasal type T/NK-cell lymphoma. Nodular sclerosing subtype was the most common in HL. The frequencies of TCL and HL were relatively low. For histological subtype, enteropathy-type TCL and primary bone marrow HL had higher frequency and poorer prognosis. The 5-year overall survival of BCL, TCL, and HL was 58.9, 34.7, and 83.5%, respectively. To the best of our knowledge, this is the largest series study of malignant lymphoma in Taiwan. Immunophenotype, histological subtype, and clinical stage play significant roles in prognosis (P < 0.05).     

FDG‐PET/CT in the management of lymphomas: current status and future directions

FDG‐PET/CT is the current state‐of‐the‐art imaging in lymphoma and plays a central role in treatment decisions. At diagnosis, accurate staging is crucial for appropriate therapy selection: FDG‐PET/CT can identify areas of lymphoma missed by CT alone and avoid under‐treatment of patients with advanced disease stage who would have been misclassified as having limited stage disease by CT. Particularly in Hodgkin lymphoma, positive interim FDG‐PET/CT scans are adversely prognostic for clinical outcomes and can inform PET‐adapted treatment strategies, but such data are less consistent in diffuse large B‐cell lymphoma. The use of quantitative FDG‐PET/CT metrics using metabolic tumour volume, possibly in combination with other biomarkers, may better define prognostic subgroups and thus facilitate better treatment selection. After chemotherapy, FDG‐PET/CT response is predictive of outcome and may identify a subgroup who benefit from consolidative radiotherapy. Novel therapies, in particular immunotherapies, exhibit different response patterns than conventional chemotherapy, which has led to modified response criteria that take into account the risk of transient pseudo‐progression. In relapsed lymphoma, FDG‐PET/CT after second‐line therapy and prior to high‐dose therapy is also strongly associated with outcome and may be used to guide intensity of salvage therapy in relapsed Hodgkin lymphoma. Currently, FDG‐PET/CT has no role in the routine follow‐up after complete metabolic response to therapy, but it remains a powerful tool for excluding relapse if patients develop clinical features suggestive of disease relapse. In conclusion, FDG‐PET/CT plays major roles in the various phases of management of lymphoma and constitutes a step towards the pursuit of personalized treatment.     

Cytomegalovirus infection following unrelated cord blood transplantation for adult patients: a single institute experience in Japan

Cytomegalovirus (CMV) infection in 28 adult patients after cord blood transplantation (CBT) from unrelated donors was compared with that after bone marrow transplantation from HLA (human leucocyte antigen)-matched related (R-BMT) and unrelated (U-BMT) donors. Positive CMV antigenaemia was seen in 19 (79%) of 24 CMV-seropositive patients at a median of 42 d (range 29-85 d) after CBT, but in zero of four CMV-seronegative patients. This did not differ significantly from values observed after R-BMT and U-BMT (66%, P = 0.22, and 60%, P = 0.15 respectively). Based on the antigenaemia results, 16 patients (67%) received pre-emptive ganciclovir therapy from a median of 47 d (range 36-67 d) after CBT. This proportion was higher than that observed after R-BMT (28%, P = 0.0048), but did not differ from that after U-BMT (50%, P = 0.21). In addition, the probability of requiring more than two courses of ganciclovir therapy after CBT (21%) was higher than after R-BMT and U-BMT (0%, P = 0.015 and 0.039 respectively). One patient (5%) developed CMV disease after U-BMT, whereas no patients developed CMV disease after CBT or R-BMT. The CMV serostatus, use of a steroid and HLA disparity affected the probability of requiring ganciclovir therapy after CBT (P = 0.024, 0.032 and 0.017 respectively). These results suggest that recovery of CMV-specific immunity after CBT is delayed when compared with BMT.     

Spontaneous improvement of chronic immune thrombocytopenia in children: experience of 56 patients at a single institute

Spontaneous improvement (SI) occurs more frequently in children with chronic immune thrombocytopenia (cITP) than in adults. It is generally accepted that, with the exception of splenectomy, conventional medical approaches for cITP do not change the natural course of the disease. Previous studies on pediatric cITP have reported prognostic factors associated with SI; however, it is important to know when such improvement occurs to enable optimal treatment strategies for cITP. Here, we report results of retrospective analysis of 56 consecutive pediatric patients with cITP at our institution. The median follow-up period after ITP diagnosis was 67 months (11–185 months). Of the 44 patients without splenectomy, 17 achieved SI at a median age of 8.5 years (2.3–16.5 years). The estimated incidence of SI was 24.6 ± 6.0 % at 36 months. In 16 of the 17 patients with SI, the recovery was achieved within 18 months from diagnosis, or at an age of less than 10 years, whereas among the 24 who did not achieve spontaneous improvement both at “an age of 10 years or more” and at “18 months or more from ITP diagnosis”, only one recovered spontaneously. A treatment decision tree, including the indication for splenectomy, should be considered based on this watershed point.     

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience

Esophagus - The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal...     

Varicella-zoster virus infection in adult patients after unrelated cord blood transplantation: a single institute experience in Japan

Varicella-zoster virus (VZV) infection was studied in 40 adult patients who underwent cord blood transplantation (CBT) from unrelated donors. Twenty-five patients developed VZV reactivation at a median of 5 months after CBT (range 1.7-26 months). The cumulative incidence of VZV reactivation after CBT was 80% at 30 months. Twenty-two patients developed localized herpes zoster. The remaining three patients developed atypical non-localized herpes zoster, which was associated with visceral dissemination in one patient. All the patients responded well to antiviral therapy. Unexpectedly, the absence of grade II-IV acute graft-versus-host disease (GVHD) was associated with a higher rate of VZV reactivation after CBT (100% versus 55%, P=0.01). These results suggest that recovery of VZV-specific immune responses after CBT is delayed even in patients without severe acute GVHD.     

The Australian experience of advance directives and possible future directions

This paper analyses the role that advance directives can play in the formation of advanced care planning. Following on from a review of the legal history of advance directives in Australia, including the common law and statutory regimes, it is argued that schemes for advance directives have not yet proven to be successful. It is proposed that what is needed is a more integrated approach, whereby advance directives are but one mechanism used in a wider concept of advanced care planning. This integrated approach should employ a variety of mechanisms including proxy decision‐making, structured concepts of best interests and clearly defined dispute resolution processes.     

Computed tomography-guided transarterial chemoembolization as the initial therapy for hepatocellular carcinoma: experience of 75 cases in a single institute

We present the survival rates of 75 nonruptured hepatocellular carcinoma cases initially treated with computed tomography-guided transarterial chemoembolization in a single institute. The 1-, 3-, and 5-year survival rates were 93.9%, 74.7%, and 47.4% in 50 Child's A cases; 75.0%, 43.6%, and 6.8% in 20 Child's B cases; and 60.0%, 40.0%, 0.0% in 5 Child's C cases, respectively. The 1-, 3-, and 5-year survival rates of the 38 estimated resectable hepatocellular carcinoma cases (Child's A, tumors limited in a single lobe) were 94.7%, 82.0%, and 44.6%, respectively. The 1-, 3-, and 5-year survival rates of the 41 cases with estimated indication for percutaneous ethanol injection therapy (tumors less than 3 cm in diameter and three or fewer in number) were 96.8%, 84.6%, and 55.5% in 31 Child's A cases; and 90.0%, 46.7%, and 0% in 10 Child's B cases, respectively. In conclusion, computed tomography-guided transarterial chemoembolization is an excellent primary therapy for hepatocellular carcinoma.     

Craving research: future directions

Many prospective clinical studies have concluded that craving does not reliably predict relapse and that the concept is of little or no clinical utility. Contrary to earlier more simplistic clinical models of addiction, more recent models do not require that craving be present for relapse to occur. New approaches to study human craving may enhance its predictive validity and yield more knowledge of its nature, course, behavioural sequelae and regulatory function in alcohol/drug consumption. These approaches include empirical research that focuses on: (1) the elucidation of the domains of craving (i.e. subjective experience, physiological responses, behavioural sequelae and their inter-relationships); (2) the temporal dynamics of craving (i.e. its course over minutes or days, as well as its natural history over the course of a drinking career); (3) the factors that may mediate/moderate/determine the development and resolution of craving; (4) studies of the predictive validity of craving measures; and (5) the development of valid methods of measuring the different domains of craving. The conclusions are that future craving research should: (1) incorporate more sophisticated general theories of behaviour (conditioning, cognitive social learning, neurobiological, and genetic); (2) apply more sophisticated and standardized measurement methods and experimental paradigms, including studies in which alcohol is made available to human subjects; and (3) effective development of new pharmacological and behavioural therapies for relapse prevention depend on greater understanding of the nature and measurement of craving.     

Lung cancer: future directions

Increasingly, basic research is being translated into clinical benefits for patients. Recent studies have shed more light on the clinical use of targeted therapies such as tyrosine kinase and angiogenesis inhibitors, and predictive factors for their clinical benefit and their role in different clinical settings are now being elucidated. New insights into the basic biology of lung cancer hold translational promise in risk assessment, early detection, molecular staging, treatment response prediction and novel therapies. New targeted agents directed at apoptotic and developmental pathways have the potential to exploit newly discovered vulnerabilities in the basic machinery of cancer. In addition, exploration of the cancer stem cell phenomenon in lung cancer may generate new approaches to prevent recurrence in surgically respectable lung cancer, and for the long-term control of extensive disease. Molecular profiling may also allow for highly individualized prognostic, predictive and therapeutic treatment plans tailored for each patient based on the molecular diagnostic profile of their tumour. Advances in genetic susceptibility, early detection and individualized therapy based on each tumour's unique biological properties all hold promise for the future management of lung cancer.