Investigation of the relationship between ionised and total calcium in dogs with ionised hypercalcaemia.

OBJECTIVES: To investigate the relationship between total and ionised calcium concentrations in dogs with ionised hypercalcaemia and to evaluate how albumin influences this relationship. METHODS: Initially, a reference interval for ionised and total calcium was established using a large population of healthy adult dogs. Our teaching hospital clinical database was searched to identify adult dogs with ionised hypercalcaemia between 2012 and 2017, a time frame when the same sample handling and analysis protocols were in place as for the healthy reference interval population. The relationship between ionised and total calcium concentrations was then examined in the ionised hypercalcaemia population. RESULTS: Based on biochemical analysis of 351 healthy adult dogs, a reference interval of 1.18 to 1.53 mmol/L for ionised calcium and 2.24 to 2.85 mmol/L for total calcium was established. Using these reference intervals, 63 dogs with ionised hypercalcaemia were identified, of which 23 did not have total hypercalcaemia. Only seven of the 23 dogs with ionised hypercalcaemia and total calcium below the upper limit of the reference interval had hypoalbuminemia. The majority of dogs with ionised hypercalcemia and normal total calcium had a modest increase in ionised calcium. CLINICAL SIGNIFICANCE: If relying on total calcium alone, more than one third of dogs with ionised hypercalcaemia will be classified as normocalcaemic and the majority of these dogs had normal serum albumin.

Long-term effects on the intelligence of children treated for acute lymphoblastic leukemia.

The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.

William Osler Abbott: his double lumen tube.

Miller as head of the GI Section, Abbott's Chief and the individual who actually constructed the original double lumen tube was logically lead author of their first paper describing a technique for intubation of the human intestine. Nonetheless, originally most people associated only Abbott's name with the tube since he arranged for its manufacture, perfected the technique by which it was used, described its use in the diagnosis and treatment of intestinal obstruction and personally carried out over 500 intubations. Three months after his death Shields Warren wrote "Not a day goes by here in the Hospital that a life is not saved by the Abbott tube" (16). Were it not for Abbott's correction of the Pilling company's first brochure the Miller Abbott tube might have been called the Abbott tube or at the very least the Abbott Miller Tube. Such a designation would not have been inappropriate when one also considers that Pete Abbott's use of the double lumen tube in studies of the gastrointestinal tract and the diagnosis and treatment of intestinal obstruction was undoubtedly a major factor in his untimely death.

Successful primary radiation therapy of adenoid cystic carcinoma of the lung.

Adenoid cystic carcinoma is a distinctive malignant neoplasm generally arising from minor salivary glands, that arises infrequently as a primary tumor in the lung. Surgery has been considered the primary treatment, with radiotherapy generally utilized as adjuvant or palliative treatment. We report a patient in whom primary radiotherapy was sucessfully applied to treat adenoid cystic carcinoma involving the distal trachea, carina, and both main stem bronchi. A total dose of 66 Gy was delivered in 2-Gy fractions over a 7-week period. Clinically and histologically complete remission was achieved without evidence of disease during a 27-month follow up.

[Preoperative irradiation and interstitial radiotherapy-hyperthermia boost in breast tumors > or = 3 cm. The Düsseldorf experience]. / Präoperative Bestrahlung mit interstitiellem Radio-hyperthermie-Boost bei Mammatumoren > or = 3 cm. Düsseldorfer Ergebnisse.

AIM: The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia. PATIENTS AND METHODS: One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy 192Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 x 2 Gy/week. Local hyperthermia with 43.5-44.5 degrees C over 60 minutes was delivered immediately before interstitial radiotherapy. RESULTS: One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases. CONCLUSION: In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.

[An absent correlation between antioxidant blood concentrations and the remission response of preoperatively treated breast carcinomas]. / Fehlende Korrelation zwischen Antioxidanzienkonzentrationen im Blut und Remissionsverhalten präoperativ behandelter Mammakarzinome.

PURPOSE: Deleterious effects of ionizing radiation and some chemotherapeutic agents are predominantly caused by reactive oxygen agents which are detoxified by antioxidants. This study was designed to evaluate the modifying effects of vitamin A-, vitamin E- and selenium serum concentrations and glutathione peroxidase activity on preoperative radio- and chemotherapy of breast cancer. PATIENTS AND METHODS: Tumor volume, vitamin A-, vitamin E-, selenium serum concentrations and glutathione peroxidase activity in circulating erythrocytes were determined in 40 patients with breast cancer before treatment. Interstitial radiohyperthermia was given initially using a single dose of 10 Gy (HDR) combined with hyperthermia between 43.5 to 44.5 degrees C over 60 minutes followed by external beam radiotherapy with 50 Gy in 5 weeks. All patients received anthracyline or anthrachinone containing chemotherapy. Tumor response was determined by histopathological examination. Patients with complete and incomplete remissions were compared using the Wilcoxon test. Pre- and posttreatment tumor-volume differences were correlated with antioxidant concentrations (Spearman correlation coefficient). RESULTS: Twenty patients (50%) achieved a complete histopathologic tumor regression. This high complete remission rate was not related to the antioxidants under investigation (vitamin A: p = 0.32, vitamin E: p = 0.44, selenium: p = 0.68, glutathione peroxidase: p = 0.3). There was no correlation to pre- and posttreatment tumor-volume-differences either (vitamin A: p = 0.89, vitamin E: p = 0.67, selenium: p = 0.41, glutathione peroxidase: p = 0.87). CONCLUSIONS: In this study serum concentrations of antioxidants had no modifying influence on tumor response in breast cancer patients following induction radio-chemotherapy and subsequent surgery. Further studies measuring tissue levels could clarify if there is any modifying influence of antioxidants on tumor remission.

Effect of recombinant human granulocyte colony stimulating factor (R-metHuG-CSF) as an adjunct to large-field radiotherapy: a phase I study.

PURPOSE: To test the feasibility of recombinant human granulocyte colony stimulating factor application during large-field radiotherapy. METHODS AND MATERIALS: Fifteen patients with clinically and histologically proven malignancy who received large-field radiotherapy entered this study. Administration of recombinant granulocyte colony stimulating factor (G-CSF) at a dose of 300 microgram subcutaneously was started on Friday and was continued on Saturday and Sunday after the first radiotherapy treatment, which began on the Monday before. In this way four courses of G-CSF were applied every Friday, Saturday, and Sunday during the radiotherapy period. Absolute neutrophil cell (ANC) and blood counts were monitored twice a week and compared to a second group of 15 patients who received large-field radiotherapy without G-CSF. Before and at the end of every cycle of G-CSF, ANC, blood counts, and biochemistry were measured. We compared the myelotoxicity of the patients treated with G-CSF with 15 patients without G-CSF treated at the same period with large-field radiotherapy, in match pair technique. RESULTS: G-CSF increased the ANC throughout the period of irradiation, and the treatment time needed for competing radiotherapy was shorter in the group who received G-CSF. Fourteen of 15 patients who received G-CSF treatment completed large-field radiotherapy without pause. Only 1 of 15 patients not receiving G-CSF was able to receive radiation treatment on schedule. Patients receiving G-CSF completed treatment with the mantle-field technique in 24 days and those with the abdominal bath technique in 26.5 days. Conversely, patients treated without G-CSF completed treatment with the mantle-field technique in 30.5 days and those with the abdominal bath technique in 36 days. The most frequent side effect was musculoskeletal pain. CONCLUSION: The prophylactic application of G-CSF during large-field radiotherapy before the onset of neutropenia was feasible in this schedule. Whether or not this shortening of treatment duration will translate into an improvement in efficacy is not clear.

The accuracy of CT-based inhomogeneity corrections and in vivo dosimetry for the treatment of lung cancer.

PURPOSE: To determine the accuracy of dose calculations based on CT-densities for lung cancer patients irradiated with an anterio posterior parallel-opposed treatment technique and to evaluate, for this technique, the use of diodes and an Electronic Portal Imaging Device (EPID) for absolute exit dose and relative transmission dose verification, respectively. MATERIALS AND METHODS: Dose calculations were performed using a 3-dimensional treatment planning system, using CT-densities or assuming the patient to be water-equivalent. A simple inhomogeneity correction model was used to take CT-densities into account. For 22 patients, entrance and exit dose calculations at the central beam axis and at several off-axis positions were compared with diode measurements. For 12 patients, diode exit dose measurements and exit dose calculations were compared with EPID transmission dose values. RESULTS: Using water-equivalent calculations, the actual exit dose value under lung was, on average, underestimated by 30%, with an overall spread of 10% (1 SD) in the ratio of measurement and calculation. Using inhomogeneity corrections, the exit dose was, on average, overestimated by 4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due to the inhomogeneity correction model. The other 2% resulted from a small inaccuracy in beam fit parameters and the fact that lack of backscatter is not taken into account by the calculation model. Organ motion, resulting from the ventilatory or cardiac cycle, caused an estimated uncertainty in calculated exit dose of 2.5% (1 SD). The most important reason for the large overall spread was, however, the inaccuracy involved in point measurements, of about 4% (1 SD), which resulted from the systematic and random deviation in patient set-up and therefore in the diode position with respect to patient anatomy. Transmission and exit dose values agreed with an average difference of 1.1%. Transmission dose profiles also showed good agreement with calculated exit dose profiles. CONCLUSIONS: The study shows that, for this treatment technique, the dose in the thorax region is quite accurately predicted using CT-based dose calculations and a simple heterogeneity correction model. Point detectors such as diodes are not suitable for exit dose verification in regions with inhomogeneities. The EPID has the advantage that the dose can be measured in the entire irradiation field, thus allowing an accurate verification of the dose delivered to regions with large dose gradients.

Carboplatin and radiotherapy in the treatment of head and neck cancer: six years' experience.

Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1- and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed.

[The significance of clinical prodromes for dosage estimation after whole-body radiation exposure]. / Die Bedeutung klinischer Prodromi zur Dosisabschätzung nach Ganzkörperstrahlenexposition.

BACKGROUND: The triage of victims after radiation injury is complicated by missing dose values and the fact that most tissues react after a latency period. PATIENTS AND METHODS: We evaluated 63 patients undergoing total body irradiation as conditioning regime before bone marrow transplantation in order to find a relation between prodromal symptoms and dose. RESULTS: Emesis after radiation exposure hints to doses greater than 1.5 Gy. A rise of body temperature above 37 degrees C up to five hours after exposure is related to doses exceeding 2.5 Gy, while an acute onset of diarrhoea is an indicator of a severe accident with more than 9 Gy. CONCLUSION: Besides blood counts and chromosome analyses a careful evaluation of prodromal symptoms can help to classify the severity of radiation accidents.

Combined radiochemotherapy with carboplatin in the treatment of advanced head and neck carcinomas.

From 1987 to 1991, 100 evaluable patients with advanced head and neck carcinomas (T2-4, N0-3) were treated with radiotherapy and simultaneous carboplatin. Tumors were located in the oral cavity in 33 patients, oropharynx in 8 patients, and hypopharynx in 7 patients. Four patients had a tumor of the epipharynx, 3 of the larynx, and 45 had involvement of two or more compartments. Radiotherapy was performed in a fractionation of 5 x 2 Gy/week up to a dose of 50 Gy. Carboplatin was administered in a dose of 60 or 70 mg/m2 from days 1-5 and 29-33. After a 2-week interval, tumor involution was evaluated and a decision was made on the patients' operability. In cases of inoperability, radiotherapy was continued up to a dose of 70-74 Gy. Thirty patients underwent surgery after 50 Gy. Eight patients showed a histologically complete remission (CR), 7 showed microscopic residual tumor, and 15 showed macroscopic tumor. Seventy patients were treated with radiotherapy and concomitant carboplatin only. Thirty-nine of them achieved a CR and 30 a partial remission (PR). The residual tumor was operable in 8 of the latter patients. Only a minor response was achieved in the remaining patient. At the end of the treatment 77 patients achieved a CR with this combined modality. From 1990 to 1992, 20 patients with locally advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, 5 days per week: total dose, 64-67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1-5 and 29-33) in a pilot study. Fifteen patients had T4 and 5 had T3 tumors. Six weeks after the end of treatment, 16 patients (80%) had CR, and PR was seen in the other 4 patients (20%). Overall and disease-free survival at 1 year was 82 and 81%, respectively. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial CR rate of 80% is encouraging. Because of the results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy with carboplatin or hyerfractionated accelerated irradiation with carboplatin. Results will be forthcoming.

The role of radiotherapy in the management of small cell lung cancer (SCLC).

In the past decade the management of small cell lung cancer (SCLC) has undergone substantial changes with respect to surgery, chemo- und radiotherapy. Due to combined chemotherapy regimens survival rates increased and the role of radiotherapy has been reevaluated. Despite this, the majority of patients treated with chemotherapy alone failed at the primary site. Several randomized studies have shown that irradiation (35 to 40 Gy) following chemotherapy has increased locoregional control rates. There is no uniform opinion about the treatment volume, fractionation schedule or optimal dose of radiotherapy. Recent reports have demonstrated better local control rates with radiation doses in excess of 45 Gy. Prophylactic cranial irradiation with 20 to 40 Gy is widely used in patients with SCLC and generally accepted in patients with complete remission after chemotherapy. Randomized studies have proven that prophylactic cranial irradiation reduces central nervous system relapses, however, no author has reported so far a significant improvement in survival.

[Radiotherapy following a breast-preserving operation in breast carcinoma]. / Strahlentherapie nach brusterhaltender Operation beim Mammakarzinom.

Between 1980 and 1988, 116 patients with invasive breast cancer were treated by limited surgery with axillary node dissection followed by radiation therapy. Radiotherapy was performed by individually computerized treatment planning. The target volume dose was 50 Gy to the whole breast followed by an electron boost of 10 Gy to the tumor bed. The median follow-up period was 59 months. The actuarial overall survival rate is 93%, and the disease-free survival 75.2%. Ten (8.6%) breast recurrences occurred. Analysis of clinical and pathological prognostic factors revealed that local control was impaired by young age, negative hormone receptors, G3-4 tumors and intraductal growth. The recurrence rate for T3- and T4-tumors was 12.5%.

Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.

[Radiochemotherapy concepts in advanced carcinomas of the mouth, oro- and hypopharynx]. / Konzepte der Radio-Chemotherapie bei fortgeschrittenen Karzinomen der Mundhöhle, des Oro- und Hypopharynx.

Among combined radiochemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radiochemotherapy, 3. adjuvant chemotherapy, 4. accelerated hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radiochemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cisplatin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy.

Phase I study of hyperfractionated accelerated radiation and simultaneous Carboplatin therapy for advanced head and neck carcinomas.

From 1990 to 1991 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/day, five days/week, total dose 64.0 to 67.2 Gy) and simultaneous intravenous application of Carboplatin (60 mg/m2, days 1 to 5 and 29 to 33) in a pilot study. Eleven patients had T4 and four had T3 tumours. At the end of treatment twelve patients had a complete tumour remission and in the others a partial tumour involution was seen. Although acute side-effects were more pronounced compared to conventional irradiation this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging.