bluuebunny/crossref_metadata_2025 huggingface dataset:
Tertiary and Salvage Rhinoplasties Using the Open Rhinoplasty Approach
Authors: Neu Bernd R
Published: February 2017

This paper reviews the results of 26 tertiary and salvage rhinoplasties, all managed by the open technique. Typically, the endonasal approach has been recommended for these difficult cases because of concerns with skin viability, and the belief that scarred nasal skin will not redrape satisfactorily. Minimal undermining has also been promoted to reduce the risk of graft shifting. Each deformity presented in this review was managed with an open exposure. There were no problems with skin viability or redraping. Cartilage grafts were required less often, and when needed, were sewn precisely into place. Tissue swelling could take 12 to 18 months to settle. This paper reinforces the need for careful preoperative planning. Potential surgical pitfalls are examined.
Tetanus: A Case Report
Authors: Mian Rizwan A , Lacey Martin S
Published: February 2017

A seven-year-old unimmunized girl presented to the emergency department with dramatic findings of tetanus eight days after puncturing herself with a wooden stick. The clinical course and treatment of generalized tetanus are reviewed. The immunization recommendations for traumatic wounds are presented.
Juvenile Hyaline Fibromatosis: A 47-Year Follow-UP
Authors: Kaddoura Imad L , Mufarrij Amjad A
Published: February 2017

Approximately 40 cases of juvenile hyaline fibromatosis have been reported to date. This condition has not previously been described in the plastic surgery literature. This report describes a case where the disease led to a complete nasal obstruction due to progressive involvement of the nose, necessitating surgical intervention. The clinical and pathological aspects of the disease, and the differential diagnosis (ie, congenital generalized fibromatosis, Von Recklinghausen disease, Winchester syndrome) are discussed.
Treatment of the Ischemic Hand in Frostbite By Revascularization with Interpositional Vein Graft and Digital Palmar Sympathectomy: A Case Report
Authors: Thoma Achilleas , Rao Jaggi , Heggtveit H Alexander
Published: February 2017

In severely ischemic hands where the microcirculation is not amenable to reconstruction, there is evidence that palmar digital sympathectomy has salutary effects. This report describes the case of a patient with a painful, ulcerated, ischemic hand secondary to ulnar artery stenosis, generalized vasospasm and intimal hypertrophy that resulted from cold injury. Surgical treatment involved an interpositional vein graft replacing a thrombotic segment of the ulnar artery and concomitant palmar digital sympathectomy. The coupling of these two microvascular procedures completely relieved the patient's symptoms, increased total blood flow and improved the vascular function of the hand. The combination of reconstruction of an occluded vessel with peripheral sympathectomy in treating difficult cases of ischemic hand injury is recommended.
Equation-based precise prediction of length of hamstring tendons and quadrupled graft diameter by various anthropometric variables for knee ligament reconstruction in Indian population
Authors: Gupta Ravi , Malhotra Anubhav , Masih Gladson David , Khanna Tanu
Published: February 2017

Preoperative prediction of hamstring tendon lengths and graft diameter for anterior cruciate ligament (ACL) reconstruction enables better preoperative planning. Presently, no study exists for Indian population where both derivation and verification of a mathematical equation for accurate prediction of hamstring graft dimensions have been done. This study was conducted in two phases: First phase ( derivation cohort): devoted to the study of correlation of length of hamstring tendons and graft diameter with various anthropometric measurements in 123 patients undergoing ACL reconstruction. Length of semitendinosus (ST) was observed to have a strong correlation with leg length ( r = 0.719), whereas that of gracilis (G) had a strong correlation with patient height ( r = 0.768). Quadrupled diameter (QD) had a strong correlation with patient height and thigh length ( r = 0.685 and 0.680, respectively). Using Pearson correlation coefficient, multiple stepwise linear regressions, and analysis of variance test, predictive equations were developed to predict the length of ST and G and QD. Second phase ( verification cohort): This was a blinded prospective study done on 300 patients to further authenticate and test the accuracy of equations developed. Here, a steady correlation was found between the observed and predicted values of length of ST, G and QD, with correlation coefficients being 0.838, 0.847, and 0.767, respectively. Thus, we can safely conclude that clinically measurable anthropometric variables can reliably predict hamstring graft dimensions. This is likely to prove useful in better preoperative planning of ligament reconstructions.
The Assessment of Learning Outcomes in Australia
Authors: Martin Linley , Mahat Marian
Published: February 2017

Since 2009 there has been increased interest in Australian universities’ ability to demonstrate that their students have acquired knowledge and skills as specified by them in the form of graduate attributes or institutional learning outcomes. This paper describes research undertaken in Australia to identify a comprehensive set of generalized learning outcomes for undergraduate study and a set of criterion-based standards to assist in grading of achievement of those outcomes. It was discovered that although Australian universities document institutional- and course-based learning outcomes for their programs, they generally do not assess students at this level. Instead, the majority of assessment of learning outcomes is at the subject level, and frequently these outcomes do not align well with the course- or institutional-based outcomes that have also been specified. In spite of this, it appears possible to identify generalized assessment tasks for subjects and use constructive alignment between subjects, course curriculum, and chosen course-based learning outcomes, which could be used to reliably measure course outcomes and compare results between universities. These developments are framed in terms of the assessment transparency framework, which provides insight into the current “as-is” situation as well as an indication of what is needed to move learning outcomes assessment toward a fully implemented “ideal” across the higher education sector.
Anchoring the innovation impacts of public procurement to place: The role of conversations
Authors: Uyarra Elvira , Flanagan Kieron , Magro Edurne , Zabala-Iturriagagoitia Jon Mikel
Published: February 2017

Public procurement is frequently touted as a means of promoting innovation at the sub-national level, but the underlying mechanisms through which this is supposed to work are seldom articulated. In particular, while the relevance of social interaction for innovation is offered as a key rationale for the use of public procurement for innovation, there is little discussion of its corresponding spatial dimensions. This paper contributes to this debate by advancing our understanding of the spatial aspects of public procurement for innovation and thus of the scope for using public procurement to achieve regional innovation policy goals. We connect the public procurement for innovation literature with the literatures on innovation-driven regional development around the notion of ‘conversations’ to capture the spatial and social aspects of interactions relevant for public procurement for innovation. Different forms of spatial anchoring of procurement are explored, presenting different challenges and opportunities for regions. We provide illustrative examples for each type, from which suggestions are derived for promoting place-based ‘innovation-friendly’ procurement.
The determination of the Sb/As content in natural tetrahedrite–tennantite and bournonite–seligmannite solid solution series by Raman spectroscopy
Authors: Apopei A. I. , Damian G. , Buzgar N. , Buzatu A. , Andráš P. , Milovska S.
Published: February 2017

Natural samples containing tetrahedrite–tennantite, bournonite–seligmannite and geocronite–jordanite from the Coranda-Hondol ore deposit, Romania, were investigated by Raman spectroscopy to determine its capability to provide estimates of solid solutions in three common and widespread sulfosalt mineral series. Raman measurements were performed on extended solid solution series (Td1 to Td97, Bnn25 to Bnn93 and Gcn24 to Gcn67, apfu). The tetrahedrite–tennantite and bournonite–seligmannite solid solution series show strong correlations between spectroscopic parameters ( position, relative intensity and shape of the Raman bands) and the Sb/(Sb+As) content ratio, while Raman spectra of geocronite–jordanite shows no evolution of Raman bands. In order to simplify the method used to estimate the Sb/(Sb+As) content ratio in tetrahedrite–tennantite and bournonite–seligmannite series, several linear equations of the first-order polynomial fit were obtained. The results are in good agreement with electron microprobe data. Moreover, a computer program was developed as an analytical tool for a fast and accurate determination of Sb/(Sb+As) content ratio by at least one spectroscopic parameter. These results indicate that Raman spectroscopy can provide direct information on the composition and structure of the tetrahedrite–tennantite and bournonite– seligmannite series.
Structural, chemical and spectroscopic re-examination of type uklonskovite leads to its redefinition
Authors: Menchetti S. , Bindi L. , Belakovskiy D. , Zaccarini F.
Published: February 2017

The crystal structure and the chemical composition of uklonskovite from the holotype material was reinvestigated to shed light on its correct chemical formula. On the basis of information gained from this characterization, we revised the formula from NaMg(SO4)OH·2H2O to NaMg(SO4)F·2H2O (F instead of OH). A careful analysis of the structural details together with a critical review of all the chemical data listed in the scientific literature for uklonskovite support our redefinition. We also present Raman data for the mineral for the first time. Our proposal was approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (voting proposal 16-J).
αIIbβ3 binding to a fibrinogen fragment lacking the γ-chain dodecapeptide is activation dependent and EDTA inducible
Authors: Zafar Hina , Shang Yi , Li Jihong , David George A. , Fernandez Joseph P. , Molina Henrik , Filizola Marta , Coller Barry S.
Published: February 2017

Key Points

Activation of αIIbβ3 is required for its ancillary site interactions with fibrinogen fragment D lacking the γ-chain dodecapeptide (‘D98’). EDTA can paradoxically induce normal αIIbβ3 to interact with fibrinogen fragment ‘D98.’
Effectiveness of preoperative chemotherapy in Wilms' tumor: results of an International Society of Paediatric Oncology (SIOP) clinical trial.
Authors: Lemerle J , Voute P A , Tournade M F , Rodary C , Delemarre J F , Sarrazin D , Burgers J M , Sandstedt B , Mildenberger H , Carli M
Published: February 2017

The results of a controlled clinical trial of preoperative radiotherapy compared to chemotherapy in patients with nephroblastoma are presented. Of 397 histologically proven cases of Wilms' tumor registered at 34 centers between January 1977 and July 1979, 164 were eligible for the trial and were randomized to receive preoperative radiotherapy and chemotherapy (group R, 76 patients) or preoperative chemotherapy (group C, 88 patients). The results were evaluated in terms of the number of surgical tumor ruptures and of local tumor extent at pathologic examination, reflecting the effectiveness of the preoperative treatment. Survival and recurrence-free survival in the two treatment groups were also taken into account. The stage distribution was comparable in the two groups, with 52% stage I tumors in group R, and 43% in group C. Significant changes in the pathologic pattern were more frequent in group R than in group C (53% versus 17%). From these data it is concluded that preoperative chemotherapy is as good as preoperative radiotherapy in terms of prevention of tumor rupture. In addition, it was shown that 43% of an unselected population of patients with Wilms' tumor could be treated without any radiotherapy when chemotherapy had been given preoperatively.
A dose and time response analysis of the treatment of Hodgkin's disease with MOPP chemotherapy.
Authors: Carde P , MacKintosh F R , Rosenberg S A
Published: February 2017

A dose-response analysis of the results of MOPP chemotherapy in 132 patients with Hodgkin's disease was carried out. Complex statistical methods were utilized including 40 different dose-time variables and multivariate logistic analyses of 21 clinical variables, both simply and in stepwise regression. These covariates were not independent, and in stepwise regression analysis only B-symptoms and the mean three-cycle rate of drug delivery significantly influenced complete remission attainment. Two parameters, bone marrow involvement (negative) and lung involvement (positive), significantly influenced the duration of complete remission. Survival was influenced adversely by pleural involvement (effusion), advanced age, and B-symptoms. Analyses indicate that the dose of all three drugs (mustard, vincristine, and procarbazine), and the rate of drug delivery during the first three cycles are important in achieving maximal complete response rates, especially for patients with B-symptoms.
Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD).
Authors: Skarin A T , Canellos G P , Rosenthal D S , Case D C , MacIntyre J M , Pinkus G S , Moloney W C , Frei E
Published: February 2017

A new combination chemotherapy program (M-BACOD) was administered to 101 patients with advanced diffuse histiocytic and diffuse undifferentiated lymphoma (DHL and DUL). High dose methotrexate (M) 3 g/m2 with leucovorin factor rescue was given on day 14 between cycles of bleomycin (B), adriamycin (A), cyclophosphamide (C), oncovin (O), and dexamethasone (D) administered every 3 weeks for 10 cycles. The complete remission rate (CR) was 72% in all 101 patients or 77% in 95 evaluable patients. The median follow-up is 3 yr 2 mo with one-third of CR patients followed beyond 4 yr. Twenty-six percent of CR patients have relapsed with a projected 5-yr survival rate of 80% (5-yr disease-free rate 65%). The overall survival of all 101 study patients reaches a plateau at 59% projected out to 5 yr. Patients with prior therapy had a significantly lower CR rate than those without prior treatment (p = 0.001); however, no other unfavorable prognostic characteristics could be identified. Relapse in the central nervous system CNS occurred in only 5.4% of CR patients. M-BACOD results in prolonged survival and possible cure in a high proportion of all patients with DHL and DUL.
Stage II nonseminomatous testicular cancer: a 10-year experience.
Authors: Vogelzang N J , Fraley E E , Lange P H , Torkelson J , Levitt S , Kennedy B J
Published: February 2017

Between 1970 and 1980, 82 patients with pathologic stage II nonseminomatous germ cell testicular carcinoma were treated at the University of Minnesota. Of the 30 patients treated with a retroperitoneal lymph node dissection, 22 (77%) relapsed. Of the 18 patients treated with retroperitoneal lymph node dissection and adjuvant radiotherapy, 12 (63%) relapsed. Sixteen patients received adjuvant chemotherapy before 1976, and 14 (87.5%) relapsed. After 1976, 18 patients received adjuvant chemotherapy (11 with cisplatin) and 2 (11%) have relapsed. No patient treated with cisplatin-based adjuvant chemotherapy has relapsed. The toxicity has been modest. Cisplatin-based chemotherapy is an effective and a safe adjuvant therapy for stage II nonseminomatous germ cell testicular carcinoma.
Fertility after chemotherapy for testicular cancer.
Authors: Drasga R E , Einhorn L H , Williams S D , Patel D N , Stevens E E
Published: February 2017

Sixty-nine patients with disseminated testicular cancer and no prior retroperitoneal lymphadenectomy treated with cisplatin, vinblastine, and bleomycin with or without doxorubicin were evaluated for semen analysis, serum gonadotropins, and testosterone. Since 1979, 41 men have been prospectively studied. Before treatment 77% were oligospermic, 17% were azoospermic, and only 6.6% could meet requirements for sperm banking. After 2 mo of therapy, 96% were azoospermic. A group of 28 patients treated between 1975 and 1979 were retrospectively evaluated. Normal sperm counts were found in 46% of those studied. Only 17% were azoospermic. Thirty-two percent have impregnated their wives, resulting in 5 healthy babies, 1 spontaneous abortion, and 3 ongoing pregnancies. These results show that (1) significant impairment of spermatogenesis exists before therapy, precluding the possibility of sperm banking in most patients, (2) combination chemotherapy in testicular cancer has substantial effects on gonadal function, rendering almost all patients azoospermic, and (3) a high degree of recovery of spermatogenesis occurs sometime after 2-3 yr from the initiation of treatment.
Clinical-pathologic study of early breast cancer treated by primary radiation therapy.
Authors: Harris J R , Connolly J L , Schnitt S J , Cohen R B , Hellman S
Published: February 2017

We performed a clinical-pathologic review of 231 patients with early breast cancer treated by primary radiation therapy. There were 27 patients with infiltrating ductal carcinoma treated with excisional biopsy whose tumors showed a constellation of histologic features: moderate or marked intraductal carcinoma in the tumor, intraductal carcinoma in the adjacent tissue, and high nuclear grade. These patients had a 5-yr local tumor control rate of 61% compared to 96% for similar patients whose tumors did not show all three features. Radiation dose to the primary tumor area influenced the likelihood of local recurrence in these 27 patients: 15 of these patients received 6000 rads or more to the primary tumor area and had a 5-yr local tumor control rate of 84%, compared to 48% for the 12 patients who received less than 6000 rads. These results indicate that a subgroup of breast cancer patients can be identified that has a high risk of local recurrence when an insufficient radiation dose (i.e., less than 6000 rads) is delivered to the primary tumor area.
Clinical trial of the effect of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) (NSC 296961) on the toxicity of cyclophosphamide.
Authors: Woolley P V , Ayoob M J , Smith F P , Dritschilo A
Published: February 2017

S-2-(3-Aminopropylamino)-ethylphosphorothioic acid (WR-2721) is reported to protect normal tissues from the effects of ionizing radiation and possibly alkylating agents as well. The present trial assessed the ability of this compound to modify the clinical toxicity of cyclophosphamide. Patients with advanced cancer first received a dose of 1000 mg/m2 cyclophosphamide intravenously and were observed for toxicity, principally myelosuppression. After the nadir in white blood cell counts and/or platelets had been documented and adequate recovery had occurred, a second course of cyclophosphamide was given, this time preceded by WR-2721 30 min earlier. In this fashion, each patient served as his own control. Doses of WR-2721 ranging from 250 to 1000 mg/m2 were tested. A total of 13 evaluable courses of WR-2721 were given with cyclophosphamide. In no instance did the prior administration of WR-2721 diminish the bone marrow toxicity of cyclophosphamide alone. At the end of the trial two additional patients received the WR-2721 in a split dose, one-half prior to the cyclophosphamide and one-half 6 hr later; again there was no protection. The side effects of WR-2721 included nausea, vomiting, hypotension, sneezing, and swelling of the tongue. We conclude that WR-2721 is a potentially toxic compound that produces no amelioration of cyclophosphamide toxicity in the doses used. Because of the severity of the side effects of WR-2721, principally hypotension, the trial was terminated after 1000 mg/m2 WR-2721 failed to protect against the toxicity of 1000 mg/m2 cyclophosphamide.
Mycosis fungoides: subcutaneous and visceral tumors, orbital involvement, and ophthalmoplegia.
Authors: Whitbeck E G , Spiers A S , Hussain M
Published: February 2017

A patient with advanced severe mycosis fungoides presented several unusual features, including prominent lesions of the palate and tongue and an orbital tumor with exophthalmos and ophthalmoplegia. A hitherto undescribed feature was the development of multiple, massive subcutaneous tumors unrelated to the dermis or to lymph nodes, and large tumors in the connective tissues of the buttock, flank, and retroperitoneum. The usual sites of extracutaneous dissemination of mycosis fungoides--lymph nodes, spleen, liver, lungs, and blood--were not demonstrably involved. This may be a new pattern of dissemination for this disease. Of practical importance is the immediate and complete relief of exophthalmos and ophthalmoplegia that was obtained with emergency radiotherapy.
Randomized study of 3 years versus 5 years of chemotherapy in childhood acute lymphoblastic leukemia.
Authors: Nesbit M E , Sather H N , Robison L L , Ortega J A , Hammond G D
Published: February 2017

Between 1972 and 1975 the Children's Cancer Study Group conducted two clinical trials for the treatment of newly diagnosed patients with acute lymphoblastic leukemia. Upon achieving 3 yr of continuous complete remission, 316 children and young adults were randomly allocated either to discontinue chemotherapy or to continue chemotherapy for an additional 24 mo. With a median follow-up from the time of randomization of 50 mo, those patients who received 3 yr of therapy have demonstrated a statistically non-significant yet higher incidence of bone marrow relapse as compared to those patients treated for 5 yr (p = 0.09). However, the proportion of patients surviving 5 yr from randomization is 93% for the 3-yr treatment group and 89% for the 5-yr treatment group (p = 0.27). No significant difference was observed between the randomized groups for the occurrence of testicular relapse (p = 0.12), central nervous system relapse (p = 0.17), or first occurrence of relapse or death (p = 0.24). The relapse-free survival of patients treated for 5 yr as compared to those treated for 3 yr was not significantly higher in males (81% versus 75%, p = 0.14) or females (89% versus 89%, p = 0.95). This randomized study did not demonstrate a significant difference between treatment for either 3 or 5 yr.
Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin.
Authors: Cohen R J , Cuneo R A , Cruciger M P , Jackman A E
Published: February 2017

A 36-year-old man being treated with cisplatinum, vinblastine, and bleomycin for testicular carcinoma developed a dense left homonymous hemianopsia, encephalopathy, and a partial nondominant parietal lobe syndrome. He subsequently had a resolution of all signs and symptoms, suggesting that these alarming events were a toxic but reversible side effect of the chemotherapy.
Long-term results of the APO protocol (vincristine, doxorubicin [adriamycin], and prednisone) for treatment of mediastinal lymphoblastic lymphoma.
Authors: Weinstein H J , Cassady J R , Levey R
Published: February 2017

Twenty-one patients with biopsy-proven mediastinal lymphoblastic lymphoma were treated with the APO protocol (vincristine, doxorubicin, and prednisone). Treatment consisted of two years of therapy with a modified doxorubicin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and intrathecal methotrexate. The median age in the group was 13 years (range, 2.5-22 years). Complete remission was obtained in 20 of 21 patients. Three patients required mediastinal irradiation for successful remission induction. Six patients have subsequently relapsed: two in the central nervous system, one in the central nervous system and testicle, one in the testicle, one in the pleura, and one in the abdomen. The median follow-up is six years (range, 16 months to 9.5 years) and a Kaplan-Meier estimate of disease-free survival at three years is 58% +/- 23% (2 SE).
Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid.
Authors: Slevin M L , Piall E M , Aherne G W , Harvey V J , Johnston A , Lister T A
Published: February 2017

The pharmacokinetics of high-dose cytosine arabinoside (ara-C) were studied in 18 patients with acute leukemia and high-grade non-Hodgkin's lymphoma. The plasma concentrations of ara-C increased in proportion to the dose over a range of 1-3 g/m2. The initial and terminal half-lives were not influenced by the dose or schedule of administration and no accumulation of ara-C occurred with repeated dosage in the same patients. These data suggest that cytidine deaminase is not saturated within this dose range. The cerebrospinal fluid (CSF) concentrations of ara-C also rose linearly with the increase in dose and varied from 347 ng/mL (1 g/m2) to 1,070 ng/mL (3 g/m2). The mean CSF concentrations of ara-C following high-dose infusions over three hours were 6%-22% of simultaneous plasma concentrations. Three hours after completion of the intravenous infusion the CSF concentrations were greater than the corresponding plasma concentrations owing to the long half-life of ara-C in CSF compared to that in plasma. These data demonstrate that therapy with intravenous high-dose ara-C given twice daily provides continuous levels in the CSF at concentrations that are likely to be of value in the treatment of central nervous system leukemia.
Resistance to methotrexate due to gene amplification in a patient with acute leukemia.
Authors: Carman M D , Schornagel J H , Rivest R S , Srimatkandada S , Portlock C S , Duffy T , Bertino J R
Published: February 2017

A patient is described with acute myelocytic leukemia refractory to conventional therapy, who also became highly resistant to methotrexate (MTX) after repeated courses of this drug. Leukemia cells from this patient were found to contain an elevated level of dihydrofolate reductase (DHFR) activity, with no change in the affinity of the enzyme for MTX. A sensitive "dot blot" assay revealed a fourfold increase in the gene copy number of DHFR. Southern blot analysis with a human DHFR cDNA probe confirmed this increase in the gene copy number, and demonstrated a similar restriction pattern with Eco R1, Hind III, and Pst 1 as seen with a highly amplified human leukemia cell line, K562. Additional DHFR fragments were detected, not seen in the K562 blot, suggesting the presence of pseudogenes, or a result of gene rearrangements occurring as part of the amplification process. Resistance to MTX in this patient was therefore ascribed to gene amplification and overproduction of DHFR.
Cytologic evidence for gene amplification in methotrexate-resistant cells obtained from a patient with ovarian adenocarcinoma.
Authors: Trent J M , Buick R N , Olson S , Horns R C , Schimke R T
Published: February 2017

To analyze if methotrexate (MTX) resistance arises from gene amplification in a patient treated clinically with MTX, the cytogenetic and drug sensitivity profile of the tumor colony forming units (TCFUs) from a 58-year-old woman with stage III well-differentiated ovarian serous adenocarcinoma was studied. This patient had not received treatment directed against her tumor for nine months before this study, but had received oral-dose MTX (2.5 mg, twice weekly) for three years for the treatment of psoriasis. Analysis of TCFUs grown in nucleoside-free media demonstrated MTX resistance at concentrations of up to 100 micrograms/mL (2.2 X 10(-4)M). Cytologic evidence for dihydrofolate reductase (DHFR) gene amplification in TCFUs was determined by in situ hybridization, using radiolabeled cDNA to DHFR mRNA. Results localized the DHFR sequences to an abnormally staining region present on chromosome 4q. This study supports the notion that alterations in gene dosage (that is, gene amplification) play a role in the development of drug resistance in spontaneous human cancers.
Clinical characteristics associated with the development of anticipatory nausea and vomiting in cancer patients undergoing chemotherapy treatment.
Authors: Morrow G R
Published: February 2017

Approximately one in four patients experiences nausea and/or vomiting in anticipation of a chemotherapy treatment by the time of their fourth treatment cycle. Anticipatory nausea and vomiting is a prevalent problem of clinical significance in the total management of chemotherapy side effects. While refractory to standard antiemetic treatment, anticipatory nausea and vomiting has been successfully treated with behavioral approaches such as systemic desensitization. The present study was designed to identify the characteristics of patients at high risk for developing anticipatory side effects. Early identification of cancer patients prone to developing anticipatory side effects could lead to preventive measures. One hundred seventy-six consecutive ambulatory patients with histologically confirmed cancer who were being treated at three geographically separate hospitals of the University of Rochester Cancer Center were studied at the time of their fourth chemotherapy treatment. Patients found to experience anticipatory nausea and vomiting were significantly more likely (P less than .001) to have four or more of the following characteristics than patients who did not report anticipatory side effects: (1) less than 50 years of age; (2) the experience of nausea and/or vomiting after their last chemotherapy treatment; (3) a description of nausea after the last treatment as "moderate, severe, or intolerable"; (4) a description of vomiting after the last treatment as "moderate, severe, or intolerable"; (5) the reporting of the side effect "warm or hot all over" after their last treatment; (6) a susceptibility to motion sickness; (7) the experience of "sweating after their last treatment"; (8) and the experience of "generalized weakness after their last chemotherapy treatment." Results support a view that anticipatory side effects are conditioned and point to practical interventions for their clinical control.
Chemotherapy of small-cell carcinoma of lung: a randomized comparison of alternating and sequential combination chemotherapy programs.
Authors: Daniels J R , Chak L Y , Sikic B I , Lockbaum P , Kohler M , Carter S K , Reynolds R , Bohnen R , Gandara D , Yu J
Published: February 2017

One hundred forty-seven eligible patients with small-cell carcinoma of the lung (SCCL) have been randomized to receive alternating (A) or sequential (S) combination chemotherapy. Initial treatment was with three cycles of VAM (A) or two cycles of POCC (S). VAM consists of VP16-213 200 mg/m2 intravenously (IV) day 1, Adriamycin (Adria Laboratories, Columbus, Ohio) 50 mg/m2 IV day 1, and methotrexate 30 mg/m2 IV day 1 repeated at 21-day intervals. POCC consists of cyclophosphamide 600 mg/m2 IV days 1 and 8, vincristine 1.5 mg/m2 (maximum, 2 mg) IV days 1 and 8, CCNU 60 mg/m2 po day 1, and procarbazine 100 mg/m2 po days 2 through 15. After initial treatment, all patients received whole brain radiation therapy (3,000 rad/10 fractions/2 wk). Patients with limited disease in addition received irradiation encompassing the tumor, hilar, mediastinal, and supraclavicular regions (5,000 rad/25 fractions/5 wk). After radiation, patients on arm A received POCC alternating with VAM; patients on arm S received POCC until progression when they were to be treated with VAM. The alternating arm was superior with respect to rate of complete remission (CR), median disease-free survival (MDFS), and median survival (MS). The advantage of alternating therapy was not as clearly demonstrated in the limited disease groups when interposition of involved field radiation delayed the initiation of the alternating schedule. In limited disease alone, comparing arm A with arm S, no statistically significant differences were noted. The CR rate was 42% v 54%, MDFS was 14 v 10 months, and MS was 16 v 10 months. In extensive disease, the CR rate was 44% v 20% (P = .03), MDFS was 6 v 4 months (P = .003), and MS was 10 v 7 months (P = .001). Improved treatment outcome in SCCL is achieved when combination chemotherapy regimens of similar effectiveness are administered in an alternating rather than sequential schedule.
A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.
Authors: Creagan E T , Green S J , Ahmann D L , Ingle J N , Edmonson J H , Marschke R F
Published: February 2017

We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.
Sudden death in cancer patients receiving lithium.
Authors: Lyman G H , Williams C C , Dinwoodie W R , Schocken D D
Published: February 2017

Lithium carbonate may attenuate the incidence and severity of infection associated with cancer chemotherapy but does not appear to improve patient survival. Of 100 patients with small-cell lung cancer receiving an identical regimen of cyclophosphamide, doxorubicin, and vincristine, 40 were assigned to treatment with lithium concurrently. To date, 60 patients have died, including 14 who died suddenly of apparent cardiovascular causes without evident progression of neoplastic disease or concurrent illness. Thirteen of the 14 sudden deaths were among 50 patients with clinical or electrocardiographic evidence of cardiovascular abnormalities before study entry. Among patients with pretreatment cardiovascular abnormalities, lithium administration was associated with a greater risk of sudden death and shorter survival. A strong interaction for risk of death was evident between lithium treatment and the use of bronchodilators. In multivariate analysis, the major predictors of patient survival were the quality of tumor response and treatment with lithium with or without bronchodilators. Lithium treatment is a major risk factor for sudden death in cancer patients with pretreatment cardiovascular changes receiving combination chemotherapy including an anthracycline antibiotic.
Continuous infusion chemotherapy: a critical review.
Authors: Vogelzang N J
Published: February 2017

With the development of reliable drug pumps and safe long-term venous access catheters, the continuous infusion of chemotherapeutic agents has become clinically feasible. The available studies on infusion therapy with 37 antineoplastic drugs are analyzed. With the majority of agents, infusion studies have either not been performed or the completed studies have failed to demonstrate improved effectiveness over bolus therapy. In some continuous infusion studies, effectiveness has been retained but with no apparent improvement in the therapeutic index. Several other drugs such as bleomycin, cytosine arabinoside, and doxorubicin have apparent improvement in the therapeutic index when given as a continuous infusion. The improved therapeutic index of the fluorinated pyrimidines when given via continuous infusion must be explored in randomized controlled studies using malignancies other than colorectal cancer. The cost effectiveness of such studies must be carefully assessed. Since this method of administration of chemotherapeutic agents offers the potential for less toxicity and retained antineoplastic effect, such investigations are highly desirable for improved patient care.
Effects of different forms of central nervous system prophylaxis on neuropsychologic function in childhood leukemia.
Authors: Rowland J H , Glidewell O J , Sibley R F , Holland J C , Tull R , Berman A , Brecher M L , Harris M , Glicksman A S , Forman E
Published: February 2017

A comparison of the late effects on intellectual and neuropsychologic function of three different CNS "prophylaxis" regimens was conducted in 104 patients treated for childhood acute lymphocytic leukemia. Of the children studied, 33 were randomized to treatment with intrathecal (IT) methotrexate alone, 36 to IT methotrexate plus 2,400 rad cranial irradiation, and 35 to IT methotrexate plus intravenous intermediate dose methotrexate. All patients were in their first (complete) continuous remission, were a minimum of one year post-CNS prophylaxis and had no evidence of CNS disease at the time of evaluation. In contrast to the other two treatment groups, children whose CNS prophylaxis included cranial irradiation attained significantly lower mean Full Scale IQs (P less than .001), performed more poorly on the Wide Range Achievement Test, a measure of school abilities, and exhibited a greater number of difficulties on a variety of other neuropsychologic measures. The poorer performance of the irradiated group was independent of sex of the patient, time since treatment and age at diagnosis. These data suggest that the addition of 2,400 rad cranial irradiation to CNS prophylaxis in ALL puts these children at greater risk for mild global loss in intellectual and neuropsychologic ability.
Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies.
Authors: Feld R , Rubinstein L V , Weisenberger T H
Published: February 2017

The Lung Cancer Study Group recently completed a double-blind adjuvant immunotherapy study, in which 473 patients with resected stage I non-small-cell lung cancer were randomized to either intrapleural BCG or placebo. The study showed no significant difference in time to first recurrence for the two treatment arms. The present report analyzes the distribution of the anatomic site of first relapse and relates this to TN staging, histology, and other appropriate risk factors. The overall rate of recurrence is significantly higher for increasing TN status and for nonsquamous as compared to squamous-cell type. However, the distribution of site of recurrence does not, in general, change with increasing TN status or with histology. Approximately 65% to 75% of the first recurrences involve distant sites, with the brain being by far the most common, regardless of TN staging or histology. The implications of this for planning future studies is discussed.
Cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer: the elimination of age trends in toxicity by using doses based on creatinine clearance.
Authors: Gelman R S , Taylor S G
Published: February 2017

Ninety-two patients with advanced breast carcinoma and no prior chemotherapy from 65 to 90 years old were treated with the combination cyclophosphamide (C), methotrexate (M), and 5-fluorouracil (F) (CMF). Because of the primary renal excretion of the first two drugs, their initial doses were calculated using a linear function of creatinine clearance. 5-Fluorouracil was given at 2/3 of the usual dose. These doses resulted in no significant age trends in almost all toxicity, response, time to failure, or cycle by cycle percentages of calculated dose actually received. There was significantly less nausea and vomiting as age increased (P less than .001) and patients greater than 80 years had a significantly shorter survival (P = .01) than patients aged 65 to 79 years. The toxicity results are in marked contrast to the experience of 126 patients aged 24 to 65 years treated with usual doses of CMF on earlier protocols. Among these younger patients there was a significant upward trend with age in diarrhea (P less than .001) and noticeable upward trends with age in hematologic toxicity (P = .06), infection (P = .06), and severe mucositis (P = .09). Patients greater than 65 years had their doses decreased less quickly than did patients less than 65 years; hence by the sixth cycle, the young and elderly patients were receiving almost the same amount of M and F.
Is it an E lesion or stage IV? An unsettled issue in Hodgkin's disease staging.
Authors: Connors J M , Klimo P
Published: February 2017

To determine whether recognized experts in the area of Hodgkin's disease would agree on the determination of stage when various types of extranodal disease are present, we asked senior investigators at 15 major centers to assign a stage to four different patients. In general, these experts agreed in cases representing the extremes of difference between localized and distant extranodal disease. However, when presented with patients with nearby but not contiguous extranodal disease of lung or bone, one half of the experts classified this as an E lesion and one half as stage IV. This disagreement in stage assignment has implications not only for individual patient treatment, but also for reporting of clinical trials. Over-assignment of stage IV has the practical result of "improving" the results of treatment of both low stage (by removing higher risk patients) and advanced stage patients (by including better risk patients). Papers reporting the results of treatment of Hodgkin's disease should include information concerning how patients with extranodal disease were separated into those with E lesions and those with stage IV disease.
Phase I trial and pharmacokinetic studies of alpha-difluoromethylornithine--an inhibitor of polyamine biosynthesis.
Authors: Abeloff M D , Slavik M , Luk G D , Griffin C A , Hermann J , Blanc O , Sjoerdsma A , Baylin S B
Published: February 2017

alpha-Difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, blocks polyamine biosynthesis and has antitumor effects in animal tumor models as well as in athymic mice implanted with human small cell carcinoma. This study was designed to determine the maximally tolerated dose of oral DFMO administered every six hours for 28 days to patients with advanced solid tumors or lymphomas. DFMO levels were measured using an ion exchange chromatographic assay and pharmacokinetic studies were performed in patients treated at each dose level. Twenty-two patients received 24 courses of DFMO. The drug was generally well tolerated. Thrombocytopenia was the dose-limiting toxicity and gastrointestinal side effects were also seen. Thrombocytopenia developed in 11 of 16 patients who had received prior chemotherapy but the four patients who had no prior chemotherapy had no decrease in the platelet count. The steady state level of DFMO achieved at the highest dose (3 g/m2) were found to be within the range needed for inhibition of ornithine decarboxylase in cell-culture systems as well as for the inhibitory activity against various human tumors in vitro. A DFMO dose of 2.25 g/m2 every six hours is recommended for phase II studies in patients previously treated with cytotoxic drugs.
A rational clinical staging system for childhood rhabdomyosarcoma.
Authors: Donaldson S S , Belli J A
Published: February 2017

There is a need for a rational and useful staging system for childhood rhabdomyosarcoma that predicts prognosis based on the biology and natural history of the disease. Important factors to consider are age, histology, tumor volume, extent of invasion, and lymphatic involvement. A clinical staging system based on a classical tumor/node/metastasis status, and which accounts for natural history as a function of site of primary, local invasion, and lymphatic or hematogenous metastases is presented. This staging system eliminates the requirement that stage is assigned following an initial therapeutic strategy and removing the implication that prognosis is determined by that strategy.
Preoperative chemotherapy and radiation therapy for patients with cancer of the esophagus: a potentially curative approach.
Authors: Leichman L , Steiger Z , Seydel H G , Dindogru A , Kinzie J , Toben S , MacKenzie G , Shell J
Published: February 2017

Twenty-one patients with squamous cell cancer of the esophagus were entered into a pilot clinical trial using preoperative chemotherapy (5-fluorouracil and cis-platinum) and radiation with the intent of improving cure rate and survival. After the preoperative treatment was complete, 15 patients (71%) were resected for cure. Seven (47%) of 15 had no histologic evidence of cancer in the resected esophagus, but two of these had microscopic cancer in resected lymph nodes. The median survival for all patients entered in the trial was 18 months, whereas for those with no cancer in the resected esophagus the median survival was 24 months. The six patients who either refused surgery (two patients) or were unresectable at surgery (four patients) died within nine months. Our conclusion in this trial is that survival and potential cure are clearly linked to successfully clearing the esophagus and nodes of histologic evidence of tumor through preoperative treatment.
Aggressive combined modality therapy for advanced local-regional breast carcinoma.
Authors: Loprinzi C L , Carbone P P , Tormey D C , Rosenbaum P R , Caldwell W , Kline J C , Steeves R A , Ramirez G
Published: February 2017

Thirty-two women with advanced local regional breast carcinoma, including nine patients with histologically diagnosed inflammatory cancer, were entered on a prospective pilot study. They were treated aggressively with initial surgery, two courses of induction chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, +/- prednisone, +/- tamoxifen (CMF [P] [T]), local-regional radiotherapy, and then maintenance chemotherapy with CMF(P) (T) alternating with doxorubicin, vincristine, +/- tamoxifen (AV[T]). The patients have been followed for 19-70 months from the time of mastectomy and their actuarial three-year survival is 65% with a median survival that has not yet been reached. Median disease-free survival (time to progression) is currently 29.5 months. Women whose gross disease could not be totally resected surgically had shorter disease-free survivals than those rendered surgically free of disease (p = 0.01). Clinically evident cardiotoxicity was seen in 25% of the patients and was felt to be primarily due to the combination of doxorubicin and radiation therapy. It was significantly more common (Plt less than 0.05) in patients with left chest irradiation (seven of 18 women) as opposed to those with right-sided irradiation (one of 14).