bluuebunny/crossref_metadata_2025 huggingface dataset:
Cesarean Scar Endometriosis: An Uncommon Surgical Complication on the Rise? Case Report and Literature Review
Authors: Khachani Imane , Filali Adib Abdelhai , Bezad Rachid
Published: February 2017

Endometriosis is defined by the presence and growth of ectopic functional endometrial tissue outside the uterus. Scar endometriosis has been described following obstetrical and gynecological surgery. It is a rare condition, though probably on the rise, due to the considerable increase of cesarean sections performed worldwide. Its physiopathology is complex; its symptomatology is rich and diverse but thorough clinical examination along with ultrasound imaging and potentially pretherapeutic cytologic evaluation are usually efficient in diagnosing the condition. Treatment is mostly surgical. We report the case of a cesarean section scar endometriosis, managed at a tertiary level center and emphasize the diagnosis and treatment options.
Faculty Perceptions of Online Teaching Effectiveness and Indicators of Quality
Authors: Frazer Christine , Sullivan Debra Henline , Weatherspoon Deborah , Hussey Leslie
Published: February 2017

Online education programs in nursing are increasing rapidly. Faculty need to be competent in their role and possess the skills necessary to positively impact student outcomes. Existing research offers effective teaching strategies for online education; however, there may be some disconnect in the application of these strategies and faculty perceptions of associated outcomes. Focus groups were formed to uncover how nursing faculty in an online program define and describe teaching effectiveness and quality indicators in an asynchronous online environment. A semistructured interview format guided group discussion. Participants (n=11) included nurse educators from an online university with an average of 15 years of experience teaching in nursing academia and 6 years in an online environment. Teaching effectiveness, indicators of quality, and student success were three categories that emerged from the analysis of data. What materialized from the analysis was an overarching concept of a “dance” that occurs in the online environment. Effective online teachers facilitate, connect, lead, and work in synchrony with students to obtain indicators of quality such as student success, student improvement over time, and student application of knowledge to the professional role.
Venovenous Extracorporeal Membrane Oxygenation as a Treatment for Obesity Hypoventilation Syndrome
Authors: Umei Nao , Ichiba Shingo
Published: February 2017

The mortality rate for respiratory failure resulting from obesity hypoventilation syndrome is high if it requires ventilator management. We describe a case of severe acute respiratory failure resulting from obesity hypoventilation syndrome (BMI, 60.2 kg/m2) successfully treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). During ECMO management, a mucus plug was removed by bronchoscopy daily and 18 L of water was removed using diuretics, resulting in weight loss of 24 kg. The patient was weaned from ECMO on day 5, extubated on day 16, and discharged on day 21. The fundamental treatment for obesity hypoventilation syndrome in morbidly obese patients is weight loss. VV-ECMO can be used for respiratory support until weight loss has been achieved.
Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: He Lei , Deng Linfeng , Zhang Quan , Guo Jianli , Zhou Jinan , Song Wenjian , Yuan Fahu
Published: February 2017

Liver biopsy still remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH), but with limitations. There is an urgent need to develop noninvasive tests that accurately distinguish NASH from simple steatosis. The purpose of this meta-analysis was to evaluate the diagnostic value of serum biomarkers including cytokeratin 18 (CK-18), fibroblast growth factor 21 (FGF-21), and combined biomarker panel (CBP) in the diagnosis of NAFLD, especially NASH. A total of 25 studies met the inclusion criteria. Pooled sensitivity and specificity values for chosen serum markers for diagnosing NASH are as follows: CK-18 (M30), 0.75 and 0.77; CK-18 (M65), 0.71 and 0.77; FGF-21, 0.62 and 0.78; and CBP, 0.92 and 0.85. CBP demonstrated better accuracy with higher sensitivity and specificity than those tested individually. Furthermore, the AUROC of CBP was 0.94 (95% CI, 0.92–0.96), compared to CK-18 or FGF-21 assay, which showed the most significant ability to distinguish NASH from simple steatosis. The results suggest that increased circulating CK-18 and FGF-21 are associated with NASH and may be used for initial assessment, but not enough. Importantly, CBP is potentially used as accurate diagnostic tools for NASH. Further prospective designed studies are warranted to confirm our findings.
Biomarkers in Allergic Airway Disease: Simply Complex
Authors: Chaker Adam M. , Zissler Ulrich M. , Wagenmann Martin , Schmidt-Weber Carsten
Published: February 2017

Clinical diagnoses of allergic airway disease need confirmation of a relevant sensitization to allergens. Serum-based component-resolved diagnosis has become increasingly popular and allows the precise assessment of specific IgE to molecular allergens. Molecular allergen diagnosis has improved our understanding of disease phenotypes in allergic patients, including cross-reactive patterns and food allergy. Beyond sensitization profiles, characterization of the (endo-)type and severity of a local allergic disease is useful for targeted therapy with biologics in advanced allergic airway disease. Surrogate markers of treatment efficacy are increasingly under validation. Prognostic and predictive biomarkers will represent a promising option for stratified prevention strategies.
Luminex LiquiChip System for the Evaluation of Cytokine Levels in Patients with Contact Dermatitis to Potassium Dichromate
Authors: Akerman Lehavit , Klein Tirza , Israeli Moshe , Fraser Abigail , Sagy Eti , Snast Igor , Mimouni Daniel , David Michael , Trattner Akiva
Published: February 2017

Background: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the “gold-standard” diagnostic method, but it poses a risk of false results. Objective: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD. Methods: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-γ, and tumor necrosis factor (TNF)-α. Results: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance. Conclusions: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD.
HIV-Associated Malignant Lymphoma
Authors: Brunnberg Uta , Hentrich Marcus , Hoffmann Christian , Wolf Timo , Hübel Kai
Published: February 2017

Acquired immune deficiency syndrome (AIDS)-related lymphomas (ARL) still represent a relevant field of clinical research. For most histological subtypes of ARL, no optimal initial therapy has been clearly defined so far. Rituximab plus chemotherapy is feasible and effective and should be offered to all patients with CD20-positive ARL regardless of their CD4 cell count. Combination antiretroviral therapy (cART) should be given concomitantly with chemotherapy, bearing in mind potential drug-drug interactions. Appropriate treatment of ARL is determined by a number of factors such as lymphoma stage, performance status, comorbidities, histological subtype, and immunosuppression. Treatment should principally be the same as in human immunodeficiency virus (HIV)-negative lymphoma patients. In HIV-related Hodgkin's lymphoma, high cure rates have been achieved with stage-adapted treatment approaches, albeit with worse outcomes compared to immunocompetent patients.
Sex Differences in Long-Term Mortality After Stroke in the INSTRUCT (INternational STRoke oUtComes sTudy)
Authors: Phan Hoang T. , Blizzard Christopher L. , Reeves Mathew J. , Thrift Amanda G. , Cadilhac Dominique , Sturm Jonathan , Heeley Emma , Otahal Petr , Konstantinos Vemmos , Anderson Craig , Parmar Priya , Krishnamurthi Rita , Barker-Collo Suzanne , Feigin Valery , Bejot Yannick , Cabral Norberto L. , Carolei Antonio , Sacco Simona , Chausson Nicolas , Olindo Stephane , Rothwell Peter , Silva Carolina , Correia Manuel , Magalhães Rui , Appelros Peter , Kõrv Janika , Vibo Riina , Minelli Cesar , Gall Seana
Published: February 2017

Background—

Women are reported to have greater mortality after stroke than men, but the reasons are uncertain. We examined sex differences in mortality at 1 and 5 years after stroke and identified factors contributing to these differences.

Methods and Results—

Individual participant data for incident strokes were obtained from 13 population-based incidence studies conducted in Europe, Australasia, South America, and the Caribbean between 1987 and 2013. Data on sociodemographics, stroke-related factors, prestroke health, and 1- and 5-year survival were obtained. Poisson modeling was used to estimate the mortality rate ratio (MRR) for women compared with men at 1 year (13 studies) and 5 years (8 studies) after stroke. Study-specific adjusted MRRs were pooled to create a summary estimate using random-effects meta-analysis. Overall, 16 957 participants with first-ever stroke followed up at 1 year and 13 216 followed up to 5 years were included. Crude pooled mortality was greater for women than men at 1 year (MRR 1.35; 95% confidence interval, 1.24–1.47) and 5 years (MRR 1.24; 95% confidence interval, 1.12–1.38). However, these pooled sex differences were reversed after adjustment for confounding factors (1 year MRR, 0.81; 95% confidence interval, 0.72–0.92 and 5-year MRR, 0.76; 95% confidence interval, 0.65–0.89). Confounding factors included age, prestroke functional limitations, stroke severity, and history of atrial fibrillation.

Conclusions—

Greater mortality in women is mostly because of age but also stroke severity, atrial fibrillation, and prestroke functional limitations. Lower survival after stroke among the elderly is inevitable, but there may be opportunities for intervention, including better access to evidence-based care for cardiovascular and general health.
Introduction: Maps of Diasporic Consciousness(簡介：海外華人意識的地圖)
Authors: Duara (杜贊奇) Prasenjit
Published: February 2017

There are several good reasons for the reluctance to call the overlapping waves of Chinese migration overseas since at least the 14th century, the Chinese diaspora. The term diaspora has come to refer to relatively homogenized groups with a strong sense of loyalty to the homeland. The overseas Chinese distributed over six populated continents are not homogenous. Yet the term diaspora is not entirely mistaken because the overwhelming bulk of the Chinese emigrant population left China over the last century and a half and developed some relationship of identity or loyalty with the homeland and the nation-state of China. To understand the diaspora historically, we need to outline the maps of consciousness—loyalties, interests, discourses, identities, projects and goals—that are relevant to the group being researched or investigated. A more embedded layer of activity often shapes and segments these maps of consciousness: these are the geopolitical and economic circumstances. The hinge between geopolitics and the maps of consciousness that has allowed Chinese communities to respond and navigate their ways through these changing circumstances have been their institutions and perhaps even more importantly, the ubiquitous and multiple networks in which most Chinese participate. Networks of native-place origins, lineages, provincial ties, language groups, religious groups and secret society groups, among others, have been historically well documented and need not detain us here. What this volume reveals however is other, perhaps more modern, networks: those constructed by the Japanese imperialist labor regime, and those developed along the dissemination of Christianity, political parties, academic research, financial capital, advertisement and even a legend of a Hokkien pirate among key global port cities.

一直以來都有一些拒絕把至少從十四世紀以來一波波出洋移居的華人通稱為「華僑」的看法，其中一個好理由是：「僑胞」所指涉的是一群相對同質、對原鄉帶有強烈忠誠的團體；而散居在六大洲的海外華人並不是同質的。但「僑胞」的概念卻又可以適切地反映出在過去一個半世紀以來，從中國移出的、並非同質的社群之間對於祖籍和中國這個民族國家所發展出的某種認同或效忠的關係。為了要歷史性地了解海外華人，我們必須探討所欲研究的各個團體所發展出來之意識的地圖──包括忠誠、利益、論述、認同、議程和目標等。這些意識的地圖鑲篏在地緣政治和經濟環境之上，後者往往會形塑或切割這些意識的地圖。透過華人的制度以及或許是更為重要的、無所不在和多元層次的華人網絡，華人社群得以回應並在各種變遷的地緣政治和經濟環境裡游移；這構成了地緣政治經濟和意識地圖之間的連結。既有的歷史資料已充分記載各種華人網絡，包括同鄉組織、宗族、省籍連帶、語言群、宗教和秘密社會等，在此毋庸贅言。本專輯卻呈現出不同的、或者是以更為現代的形式所出現的各種網絡：日本殖民主義主導下的勞工移民，以及華人在各全球港口之間散布的基督教、政黨、學術研究、金融資本、廣告甚至是閩南海盜傳說。 (This article is in English).
A Ghost and His Apparition Roam the South China Sea: Limahong and the Dream of a Hokkien Nation (南中國海上陰魂不散的鬼魅及其幻影：林鳳和一個閩南民族的夢)
Authors: Guingona (顧恒) Phillip B.
Published: February 2017

Through an analysis of three “hauntings” that spanned the sixteenth to twenty-first centuries, this article highlights recurring instances of Hokkien political maneuvering when the possibility of an autonomous Fujian or maritime-based Hokkien empire threatened the contrasting imperial and national missions of Spanish, Chinese, and Filipinos in the region. The first haunting occurred in the Spanish-controlled Philippines from the sixteenth to nineteenth centuries when the imagined threat of an invasion from China led to reactionary pogroms and a schizophrenic Spanish China-policy. The second haunting occurred in the early twentieth century when Chinese nation-makers were challenged by a nascent Hokkien nationalism that threatened to tear Fujian from China. The final haunting took place in the pages of novels and history books from the Philippines in the twentieth and twenty-first centuries; Filipino authors attempted to create and reinforce a stereotyped image of Chinese as apolitical business-minded people.

透過對十六世紀到二十一世紀的三波「著魔」現象的分析，本文強調每當以福建為主體或以海洋活動為基礎的閩南華人有可能發展成一政體，從而威脅到包括西班牙、中國和菲律賓等帝國和民族主義者的使命時，針對閩南認同的政治工作就會一次又一次地在這個地區出現。第一次著魔現象出現在十六到十九世紀、西班牙統治時期的菲律賓。當時一旦有任何可能來自中國的入侵，就會引起西班牙在與中國相關政策上極大的精神恐慌。第二次的著魔現象發生在二十世紀初期，當時中國民族建構者面對新興的閩南民族主義試圖將福建從中國分離出來的挑戰。最後一波的著魔現象呈現在菲律賓二十世紀及二十一世紀的小說和歷史書籍裡。菲律賓作者嘗試去創造並強化華人對政治冷感、只是在商言商的刻版印象。 (This article is in English).
Dianthus borbonicus (Caryophyllaceae), a new species from Sicily
Authors: Brullo Salvatore , BRULLO CRISTIAN , COLOMBO PAOLO , GALDO GIANPIETRO GIUSSO DEL , ILARDI VINCENZO , PERRONE ROSARIA
Published: February 2017

Dianthus borbonicus a new species occurring in North-Western Sicily is described and illustrated. It is a rare chasmophyte belonging to the D. sylvestris group, which is exclusive of a rupestrian stand near Rocca Busambra (Ficuzza). Its macro- and micromorphological features (seed testa sculptures, and leaf anatomy), ecology, conservation status and a comparison with the related species are provided too.
A new species of Phaenostoma d’Orchymont, 1937 (Coleoptera: Hydrophilidae) from Brazil
Authors: CLARKSON BRUNO , TAKIYA DANIELA MAEDA
Published: February 2017

A new species of Phaenostoma d’Orchymont, 1937 (Hydrophilidae: Sphaeridiinae: Coelostomatini) from Brazil is des-cribed and illustrated. Phaenostoma tupiniquim sp. nov. is described based on an adult male specimen from the Caatinga biome in Ceará State (Northeastern Brazil) and two specimens from uncertain localities, but most likely Mato Grosso and Pará States (Central-western and Northern Brazil, respectively). An updated key to the five known species is provided.
Histologic conversion in the non-Hodgkin's lymphomas.
Authors: Acker B , Hoppe R T , Colby T V , Cox R S , Kaplan H S , Rosenberg S A
Published: February 2017

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.
The treatment of stage IIIA Hodgkin's disease.
Authors: Lister T A , Dorreen M S , Faux M , Jones A E , Wrigley P F
Published: February 2017

Sixty consecutive previously untreated adults with surgically confirmed stage IIIA Hodgkin's disease (39 stage IIIA1, 21 stage IIIA2) began therapy at St. Bartholomew's Hospital between 1969 and 1981. Prior to 1973, treatment consisted of total nodal irradiation (TNI). From 1973 until 1978 patients were randomly allocated to receive either TNI or cyclic combination chemotherapy of mustine, vinblastine, prednisolone, and procarbazine (MVPP) as part of a Medical Research Council Trial. Since 1978 treatment has been allocated according to substage, those with stage IIIA1 receiving TNI and those with stage IIIA2 receiving MVPP. Seven patients received "non protocol" therapy (extended mantle radiotherapy in three patients, mantle and MVPP in four patients), and have been excluded from the study. Complete remission was achieved in 48 of 53 patients regardless of substage or therapy. Seven have relapsed, one after MVPP and six after TNI. The predicted freedom-from-relapse after MVPP was 96% compared with 60% after TNI, both at 10 years (p less than 0.01). The relapse pattern was the same for both substages in the group receiving TNI. Although overall survival of patients receiving TNI was identical to that of those receiving MVPP, TNI must be considered inappropriate therapy for stage IIIA Hodgkin's disease if permanent freedom-from-recurrence is the goal.
Methyl-CCNU, 5-fluorouracil, vincristine, and streptozocin (MOF-STREP) in metastatic colo-rectal carcinoma.
Authors: Weltz M D , Perry D J , Blom J , Butler W M
Published: February 2017

Forty patients with metastatic colorectal carcinoma who had received no prior chemotherapy were entered onto a trial of methyl-CCNU, 5-fluorouracil, vincristine, and streptozocin (MOF-STREP). Ten of 40 (25%) responded. Two patients (5%) achieved a complete response and eight patients (20%) a partial response. In addition, 10 patients previously treated with chemotherapy received the MOF-STREP regimen; 1 of 10 (10%) responded. The duration of the complete responses were 5 and 16 mo, respectively. The median duration of the partial responses was 4 mo with a range of 1-16 mo. The median survival of the 11 responders was 14 mo. Median survival of the 39 nonresponders was 5 months. Responders lived significantly longer than nonresponders (p = 0.03, log-rank). Toxicity was severe with nausea and vomiting common after streptozocin and myelosuppression requiring dose reductions in 70% of patients. We compare our findings using this regimen to those of two previously reported trials.
Functional organization of the hematopoietic stem cell compartment: implications for cancer and its therapy.
Authors: Hellman S , Reincke U , Botnick L , Mauch P
Published: February 2017

Recent discoveries indicate that hematopoietic stem cells have limits on their proliferative capacity and are unable to divide indefinitely. There is great heterogeneity within the compartment as to the extent of this proliferative limitation. At any given time it appears that hematopoiesis is maintained by the progeny of only a few stem cells. When these are exhausted the progeny from other stem cells take their place. The observations of proliferative limitation, heterogeneity, and clonal succession must be incorporated into any model of stem cell organization. These new discoveries and the models incorporating them have important clinical implications. They may explain the inability of normal tissues to develop drug resistance and they also offer a mechanism by which cell renewal systems decrease the development of malignancies. In the selection of chemotherapeutic agents not only the effectiveness of the drug upon the tumor must be considered, but also how specific agents affect the stem cell compartment. These data have important implications in the use of bone marrow transplantation for both malignant and nonmalignant disease.
Diagnostic accuracies of clinical studies in patients with small cell carcinoma of the lung.
Authors: Chak L Y , Paryani S B , Sikic B I , Lockbaum P , Torti F M , Carter S K
Published: February 2017

The diagnostic accuracy of clinical studies done in 38 patients with small cell carcinoma of the lung was analyzed by comparing the test results to autopsy findings. The chest radiograph was accurate in 31 of 38 patients (82%). The accuracy of the chest radiograph was higher in evaluating the lung parenchyma and mediastinum than in evaluating the hilum and pleura. Computerized tomographic brain scan was accurate in 11 of 12 patients. However, all the diagnostic studies used for assessing the liver, including physical examination, serum liver enzyme and bilirubin measurements, and radionuclide liver scan, were only moderately accurate. More accurate studies for detecting liver metastasis in patients with small cell carcinoma are needed.
Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.
Authors: Weiss G R , Garnick M B , Osteen R T , Steele G D , Wilson R E , Schade D , Kaplan W D , Boxt L M , Kandarpa K , Mayer R J
Published: February 2017

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.
Review of the use of marrow transplantation in the treatment of non-Hodgkin's lymphoma.
Authors: Appelbaum F R , Thomas E D
Published: February 2017

High-dose chemoradiotherapy followed by marrow transplantation has become a widely used form of therapy for patients with acute leukemia. Because of the success of marrow transplantation in the treatment of this disease, there has been increased interest in the possible application of marrow transplantation to the treatment of other malignancies known to be sensitive to chemotherapy and radiotherapy. In this paper we review the rationale behind the application of marrow transplantation to the treatment of non-Hodgkin's lymphoma and the results that have been achieved to date.
Cranial nerve involvement in children with leukemia and lymphoma.
Authors: Paryani S B , Donaldson S S , Amylon M D , Link M P
Published: February 2017

Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.
Four-drug combination chemotherapy (methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU) for non-small cell bronchogenic carcinoma: a Cancer and Leukemia Group B study.
Authors: Green M , Horton C , Spaulding M , Silver R T , Berenberg J , Kennedy B J , Pajak T F , Comis R
Published: February 2017

Ninety-eight evaluable patients with nonresectable regional or metastatic non-small cell bronchogenic carcinoma were treated with a four-drug combination chemotherapy program of methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU (MCHC). Fifteen partial or complete responses (15%) were obtained, all but one of which occurred in good performance status (0-1) patients. While "responders lived longer than non-responders", this was due more to initial performance status among responding patients than to achievement of partial (greater than 50%) or complete disease regression. Evaluation of those patients with good performance status (PS 0-1), indicated no statistically significant differences in median survival time for complete response and partial response patients compared to patients with "improved" or "stable" disease status in this group. This combination of modestly active single agents produced disappointing results in our lung cancer population. A search for more active single agents in lung cancer is necessary.
The true predictive value of the human tumor stem cell assay: does a workable assay select for treatment responders?
Authors: Hug V , Thames H , Johnston D , Blumenschein G , Drewinko B , Spitzer G
Published: February 2017

In practice, the human tumor clonogenic assay is workable for less than half of the patient population to which it is applied, since the remainder of the specimens fail to produce sufficient numbers of colonies. Thereby a bias may be introduced which could result in a false predictive value positive of the test. It is therefore necessary to compare the responses to treatment of patients whose tumors could be assayed in vitro to those whose tumors failed to grow adequately, to assure that the prevalence of treatment responders has not changed within the group of patients for which the assay worked. From an analysis of the treatment response of 70 patients with stage III and IV ovarian carcinomas and 70 patients with stage IV breast cancer, no selection bias did occur and no preferential in vitro growth of tumor samples from patients with treatment response was found.
Continuous infusion high-dose cytosine arabinoside in refractory childhood leukemia.
Authors: Ochs J , Sinkule J A , Danks M K , Look A T , Bowman W P , Rivera G
Published: February 2017

Ten pediatric patients with refractory leukemia received continuous infusion high-dose cytosine arabinoside (ara-C) according to one of two escalating dosage schedules: (1) a 500-mg/m2 rapid infusion loading dose followed by 3.5 g/m2 per day continuous infusion daily for four consecutive days, or (2) a 600-mg/m2 rapid infusion loading dose followed by 5.0 g/m2 per day continuous infusion daily for four consecutive days. Major toxicity at the lower dosage level was grade IV hematopoietic aplasia of three weeks' duration. At the higher dosage level, there was a prohibitive toxicity in multiple organ systems including transient noncardiogenic pulmonary edema, fungal infections, peritonitis, severe diarrhea, transaminase elevations, and one treatment-related death due to acute renal failure. In contrast to other methods of administration of high-dose ara-C, no CNS toxicity occurred. Oncolytic responses were seen in all patients and two achieved brief, partial remissions. Steady-state plasma ara-C concentrations were 13 to 40 mumol/L at the 3.5-g/m2 dosage level and 10 to 225 mumol/L at the 5-g/m2 dosage level; CSF concentrations at both dosages ranged from 2 to 5 mumol/L. Intracellular levels and ratios of 1-beta-D-arabinofuranosylcytidine-5' triphosphate and endogenous deoxycytidine 5' triphosphate in marrow blasts varied widely at steady state during infusion. No positive correlation existed between steady-state plasma ara-C levels, toxicity, oncolytic effect, or intracellular nucleotide concentration.
Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.
Authors: Craig J B , Jackson D V , Moody D , Cruz J M , Pope E K , Powell B L , Spurr C L , Capizzi R L
Published: February 2017

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.
In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses.
Authors: Georgoulias V , Iskandar Y L , Amesland F , Ribaud P , Mathé G , Jasmin C
Published: February 2017

The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.
The role of computed tomography of the chest in the management of small-cell lung cancer.
Authors: Griffin C A , Lu C , Fishman E K , Khouri N , Markman M , Siegelman S S , Abeloff M D
Published: February 2017

Despite the wide application of computed tomography (CT) in the diagnosis and management of lung cancer, the role of this diagnostic modality in the management of small-cell lung cancer (SCC) has not yet been defined. We therefore compared information gained from routine chest radiography (CXR) and CT scans performed on 32 patients with SCC who were treated on an intensive chemotherapy-radiotherapy protocol. Seventy-nine pairs of CXRs and CT scans were retrospectively reviewed. We found that although CT delineates a greater extent of intrathoracic disease in each of nine anatomic areas evaluated than does CXR, agreement between CT and CXR was significant for all areas except the pericardium. Pericardial thickening was seen only on CT scan and is more frequent in SCC patients than has previously been appreciated, but both its etiology and prognostic significance are unclear at this time. CT also allowed interpretation of disease status in cases where radiation-induced fibrosis made interpretation of the CXR impossible. We do not recommend routine use of chest CT at time of diagnosis of SCC, but we recommend that its use be reserved for evaluation of new symptoms or suspected relapse, or when radiation fibrosis on CXR is severe.
Identification of early relapsing patients with adult acute nonlymphocytic leukemia by bone marrow biopsy after initial induction chemotherapy.
Authors: Cassileth P A , Gerson S L , Bonner H , Neiman R S , Lusk E J , Hurwitz S
Published: February 2017

Bone marrow biopsies obtained from 69 adult patients with acute nonlymphocytic leukemia (ANLL) six to 10 days after initial induction chemotherapy were reviewed blindly to detect the presence of residual leukemia. Discrimination between the presence or absence of leukemic cells was provided by assessment of the numbers, clustering, and nuclear morphology of blasts and promyelocytes. Twenty-six patients had frank leukemia, 25 had no apparent leukemic cells, and 18 had focal residual leukemia. Of 25 patients whose bone marrow contained no detectable residual leukemic cells, 21 gained complete remission without further chemotherapy. These patients had a median duration of remission of 278 days, with five patients still remaining in remission for 578-882 days. Similarly, all of the 18 patients who had focal residual leukemia achieved complete remission without additional chemotherapy; however, all have relapsed with a median duration of remission of 163 days. This study indicates that patients with foci of residual leukemia in their one-week posttreatment bone marrow samples readily achieve remission, but carry a substantial leukemic burden that increases the likelihood of early relapse.
Childhood Hodgkin's disease: patterns of relapse.
Authors: Russell K J , Donaldson S S , Cox R S , Kaplan H S
Published: February 2017

One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.
Brain metastases in patients with renal cell carcinoma: prognosis and treatment.
Authors: Decker D A , Decker V L , Herskovic A , Cummings G D
Published: February 2017

Thirty-four patients with renal cell carcinoma and brain metastases were reviewed to define important prognostic factors and treatment results. The following covariates were analyzed to determine their influence on survival: disease-free interval, serum calcium, number of central nervous system (CNS) metastases, weight loss, performance score, age, radiation therapy, surgery, and surgery plus radiation. The mean survival for all patients was 7.0 months (range, seven days to 32 months). The patients with a good performance score of 0-2 survived significantly longer (mean survival, 10.2 months) than those with a poor performance score of 3-4 (mean survival, 2.8 months; p = 0.0019). Surgery was associated with significantly improved survival (mean survival, 13.8 months versus mean survival, 4.2 months; p = 0.014). However, all the surgical patients were from the good performance score group, suggesting patient selection. Radiation was associated with an improved mean survival of 8.6 months versus 3.2 months. Performance score is a significant prognostic factor. Furthermore, the data support treatment with radiation therapy for patients with multiple CNS metastases and surgery followed by postoperative radiation therapy for patients with single CNS metastases.
Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study.
Authors: Quagliana J M , Stephens R L , Baker L H , Costanzi J J
Published: February 2017

A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.
A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.
Authors: Begg C B , McGlave P B , Bennett J M , Cassileth P A , Oken M M
Published: February 2017

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.
Malignant mesothelioma of the tunica vaginalis testis.
Authors: Antman K , Cohen S , Dimitrov N V , Green M , Muggia F
Published: February 2017

Eighteen patients with malignant mesothelioma of the tunica vaginalis testis have been previously reported. These and the six patients reported here are reviewed for natural history and response to treatment. This tumor should be considered in men of any age with scrotal masses that include a hydrocele. Staging procedures should include computerized tomography scanning of the chest and abdomen. Inguinal orchiectomy appears to be the optimal primary surgical approach. Intraabdominal disease found at diagnostic laparotomy may be effectively treated by surgery and/or abdominal radiotherapy. Clinical features such as a long asymptomatic interval from initial presentation to clinical recurrence were observed and are also worthy of emphasis. Thus, serial follow-up is advised. Upon recurrence, treatment remains unsatisfactory but some responsiveness to chemotherapy has been noted. Doxorubicin-containing regimens were administered to five patients with measurable pulmonary nodules resulting in two partial regressions by standard criteria.
Angiotensin-I-converting enzyme in cancer patients.
Authors: Mansfield C M , Kimler B F , Henderson S D , Vats T S , Svoboda D J
Published: February 2017

Serum levels of angiotensin-I-converting enzyme (ACE) were assayed before, during, and after radiation therapy in 209 patients receiving treatment for neoplastic disease. Daily fluctuations in the measured ACE levels were minimized by comparing all patient values to that of a simultaneously run sample from a standard source of serum obtained by pooling sera from young, healthy volunteers. Most of the patients tested presented with a normal to low ACE level, with the mean value for all patients being 70% of the standard value. More patients with primary lung cancer displayed values that were low (107 of 120) than did patients with disease outside the lung (44 of 78), this difference being statistically significant at p less than 0.001. In addition, more patients with lung cancer had values less than 70% of the standard than did patients with disease outside the lungs. These initial results suggest that monitoring of serum ACE levels may be useful in the management of patients with malignant disease in the lung.
The biology and treatment of superficial bladder cancer.
Authors: Torti F M , Lum B L
Published: February 2017

Management of the superficial bladder cancer patient consists of two complementary but separate therapeutic goals: treatment of the existing tumor(s) and prevention of tumor recurrence. At present, the stage, grade, and multicentricity are the major determinants in the natural and therapeutic history of the disease. Although intravesical instillation of chemotherapeutic agents has been used for greater than 20 years, neither its exact role nor the optimal dose or schedule of administration have been established. To date, no dramatic differences in efficacy between the agents commonly used for intravesical chemotherapy, either as definitive therapy or prophylaxis, have been appreciated. These agents do appear to lower the recurrence rate as well as extend the disease-free interval. Since the most thorough experience is with thiotepa, it is the drug against which other agents should be compared in terms of both efficacy and toxicologic evaluation. Different administration schedules and methodologies need further study, such as the utility of continuous bladder irrigation, the use of sequential chemotherapeutic agents to gain cell synchronization, and the use of multiple drug regimens. Because there are multiple factors that influence the occurrence and recurrence of bladder cancer, combined modality therapy deserves testing. Modes of therapy that could be used together because they act through different mechanisms are intravesical chemotherapy, radioactive needle implants, carcinogen modifiers such as pyridoxine, chemoprotective agents such as retinoic acid, and immune stimulants such as BCG. These studies should be performed in a randomized prospective controlled fashion, which may require cooperative multi-institutional involvement to accrue adequate numbers of patients. At this time there are a number of important questions that remain to be answered concerning the treatment of superficial bladder cancer: (1) does this mode of therapy affect overall survival, (2) does prophylactic intravesical chemotherapy alter the incidence of subsequent muscle invasive disease, (3) does intravesical chemotherapy alter the sites, incidence, or responsiveness to systemic chemotherapy of subsequent metastatic disease, and (4) and what is the optimal timing and duration of prophylactic therapy from a cost-effectiveness standpoint?