Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial.

BACKGROUND: Human Papillomavirus oropharyngeal carcinoma (HPVOPC) has better progression free (PFS) and overall survival (OS) than non-HPVOPC. Standard-dose chemoradiotherapy (sdCRT) results in significant acute toxicity and late morbidity. We hypothesized that after induction chemotherapy (IC), reduced dose chemoradiation (rdCRT) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity. METHODS: Patients with p16+, previously untreated, locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles of IC with docetaxel, cisplatin and fluorouracil (TPF). Clinical responders who were HPV positive by type-specific PCR were randomized 1:2 to sdCRT (7000 cGy) or rdCRT (5600 cGy) with weekly carboplatin. The endpoints of the study were 3 year PFS and OS. RESULTS: 23 patients were enrolled, 22 were evaluable for TPF toxicity and 20 were randomized, 8 to sdCRT and 12 to rdCRT. Sixteen (80%) were HPV 16+ and 4 (20%) were other high risk (HR) variants. Fourteen (70%) had high risk features: T4, N2c, or N3. Median follow up was 56 months (range 42-70). Three-year PFS/OS for sdCRT and rdCRT are 87.5% vs 83.3% (log-rank test p = 0.85), respectively. All 3 failures are locoregional within 4 months of completion of CRT; 2 were in HR variants (50%). CONCLUSIONS: rdCRT after IC resulted in similar PFS/OS compared sdCRT. These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC. Molecular HPV with variant testing and smoking history are necessary for de-escalation trials.

[Solid and papillary epithelial neoplasm of the pancreas. Report of 2 cases]. / Neoplasia epitelial sólida y papilar del páncreas. Descripción de dos casos.

Solid and papillary epithelial tumor of the pancreas occurs mainly in young women and its main characteristic is the appearance of an abdominal mass which progressively increases in size. The radiologic, surgical and pathological correlation shows that it is a tumor of low grade malignancy with a favorable prognosis, after therapy and according to the location of the tumor. The authors report the clinical history of the first two confirmed cases of this entity in Panama, which occurred in 1985 and 1992, respectively, in women less than 25 years of age.

Neoplasia epitelial sólida y papilar del páncreas: descripción de dos casos / Solid and papillary epithelial neoplasm of the pancreas: report of 2 cases

Solid and papillary epithelial tumor of the pancreas occurs mainly in young women and its main characteristic is the appearance of an abdominal mass which progressively increases in size. The radiologic, surgical and pathological correlation shows that it is a tumor of low grade malignancy with a favorable prognosis, after therapy and according to the location of the tumor. The authors report the clinical history of the first two confirmed cases of this entity in Panama, which occurred in 1985 and 1992, respectively, in women less than 25 years of age

Comparative sensitivity of different methods to detect and quantify circulating fibrinogen/fibrin split products.

This study compared the sensitivity of three methods: staphyloccocal clumping test, SCT (Sigma and Calbiochem-Behring, CBC, reagents); Thrombo-Wellcotest (TWT); and Dade fibrinogen degradation products detection set, to quantify fibrinogen/fibrin split products (FSP) in blood samples from 696 patients and 124 normal donors using fibrinogen as the reference value. The Dade method gave quantitative results closely approaching the stated amount of fibrinogen. The SCT using Sigma reagents gave higher "fibrinogen" values, while the CBC reagents gave markedly lower "fibrinogen" values. The TWT detected only 25% of the fibrinogen standard. Detection of FSP following plasmin digestion of fibrinogen varied considerably for each test. The TWT, insensitive to most of the native fibrinogen, detected most of the FSP following only 15 minutes of plasmin digestion. In contrast, both assays relying on the SCT were completely negative after 24 hours of plasmin digestion. All four methods yielded FSP titers of less than 10 micrograms/mL in 97 (78.2%) of 124 blood samples from normal donors. The SCT Sigma reagents consistently gave results of less than 10 micrograms/mL in all normal donors. No instance of an FSP value greater than 40 micrograms/mL was noted for the 124 normal donors. Of the 696 patient blood samples tested, the Dade assay gave the highest or equally highest (with respect to another FSP method) value in 604 (87%) cases; the Sigma SCT did so in 360 (52%); the TWT in 316 (45%); and the CBC assay in 184 (26%) cases. The Dade test classified the largest number of blood samples, 328 (47.1%), in the greater than 10 less than 40 micrograms/mL titer category; however, the proportion of cases (32.2%) in which this test yielded values greater than 40 micrograms/mL was about the same as those produced by the Sigma SCT (29.9%) and TWT products (25.8%). Thus, with the exception of the normal (less than 10 micrograms/mL) and the suspicious (10-40 micrograms/mL) range, all three methods (Dade, Sigma, and TWT) are comparable in their abilities to detect abnormal levels of FSP. In the normal range, the Dade method will yield results that are frequently in the suspicious range. The CBC was noticeably inferior in detecting both suspicious and frankly abnormal values of FSP. Eight patients with acute leukemia were monitored sequentially with FSP and fibrinopeptide A (FpA) assays during their first course of chemotherapy. In all instances, elevated FpA levels correlated with elevated FSP values, as determined by the Dade, Sigma, or TWT assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Rh-incompatible platelet transfusion therapy in cancer patients. A study of 30 cases.

The clinical histories of 30 consecutive Rh0D-negative oncology patients transfused with Rh0D-incompatible platelet concentrates were analyzed. No evidence of sensitization to the Rh0D antigen was found whatsoever, in spite of the large numbers of Rh0D-incompatible platelet transfusions given to these patients. The results of this work seem to indicate that patients with malignant diseases, who are undergoing various forms of antineoplastic therapy, are immunomyelosuppressed, and have severe thrombocytopenia, can safely receive platelets from Rh0D-positive donors without developing evidence of immunization to Rh0D antigens.

Subacute toxicity of intravenous dimethyl sulfoxide in rhesus monkeys.

Daily iv doses of 3 g/kg dimethyl sulfoxide in a 40% solution were given to rhesus monkeys for 9 consecutive days. The monkeys were monitored before and after treatment for 4 mo for changes in blood chemistry, hematology, urine, and ocular, neurological, and cardiovascular systems. At the end of the study all animals were sacrificed and gross and microscopic pathological examinations were performed. No significant or long-lasting changes were recorded in any of the parameters studied when these data were compared to those for saline controls.

Histochemical fluorescence of tissue and brain monoamines: results in 18 minutes using the sucrose-phosphate-glyoxylic acid (SPG) method.

A rapid and sensitive modification of the glyoxylic acid method for the histofluorescent visualization of catecholamines and serotonin in mammalian brain, and other tissues, from cryostat sections is described. The procedure uses a phosphate-sucrose buffer solution combined with 1% glyoxylic acid. Tissues are reacted for 3 s at room temperature. Catecholaminergic cell bodies, pre-terminal, and terminal varicosities, well-localized and brightly fluorescent, are seen throughout cortical and subcortical structures. Serotoninergic cells show a weak fluorescence in rat and mouse brain but a strong fluorescence in dog and monkey brain.

Dexamethasone and DMSO in experimental transorbital cerebral infarction.

Twenty rhesus monkeys were used to evaluate the effects of dexamethasone and dimethyl sulfoxide (DMSO) following experimental occlusion of the middle cerebral artery (MCA) for 17 hours. Animals were initially treated after four hours while the MCA remained occluded and a series of tests was used to evaluate the neurological and cerebral status of each monkey for seven days. The results show that the gross, microscopic and angiographical picture of dexamethasone and no-treatment controls was practically identical. In contrast, DMSO-treated monkeys showed significant protection from the severe neurological deficits seen in the other groups. It is concluded that DMSO has a positive effect in reducing the neurological deficits seen in this model and may be potentially useful in clinical emoblic stroke.

A methodological approach to rapid and sensitive monoamine histofluorescence using a modified glyoxylic acid technique: the SPG method.

A modified approach of the glyoxylic acid (GA) condensation reaction for the visualization of biogenic amines in tissue is described. Cryostat sections are used from brain or extracerebral tissue in dog, monkey, rat and mouse and exposed for 3 s to a room temperature solution containing sucrose-potassium phosphate-glyoxylic acid (SPG). The tissues are air dried and heated in an oven for 5 min. The complete precessing time from fresh tissue to microscopic examineation takes 18 min. Morphologically sharp and brightly fluorescent monoamine-containing neurons, pre- and terminal axons are seen against a dark parenchymal background without drug pre-treatment. The SPG method retains the high specific sensitivity for monoamines previously described in the original technique but is, in addition, more rapid and simple and is easily accissible as a research tool to investigators inexperienced in histofluoresecence techniques.