Mortality and cancer incidence following radiotherapy for seminoma of the testis

The model peptides glycylglycyltyrosylalanine (Gly-Gly-Tyr-Ala), glycylglycylthreonylalanine (Gly-Gly-Thr-Ala) and glycylglycylserylalanine (Gly-Gly-Ser-Ala) were phosphorylated at the hydroxyl groups of their tyrosyl, threonyl and seryl residues, respectively, and characterized by 31P and 1H NMR spectroscopy. The pKa-value of the phosphoryl group in the tyrosine-containing peptide determined from the pH dependence of chemical shifts is 5.9, the 31P chemical shifts at low pH (4.0) and high pH (8.0) are -3.8 and 0.2 ppm, respectively. Phosphorylation also leads to significant shifts of the 1H NMR resonances of the tyrosine residue; the amide resonance is shifted -0.02 ppm, the H alpha resonance 0.06 ppm, the H beta resonances 0.10 and -0.04 ppm, the H delta resonances 0.02 ppm and the H epsilon resonances 0.26 ppm. The pKa-value of the phosphoryl group in the threonine peptide determined from the pH dependence of chemical shifts is 6.1; the 31P chemical shifts at low pH (4.0) and high pH (8.0) are -0.1 and 4.8 ppm, respectively. The corresponding values for the serine peptide are 6.1 (pKa), 0.6 ppm and 4.9 ppm. Phosphorylation also leads to significant shifts of the 1H NMR resonances of the threonine and serine residues. In the threonine residue the amide resonance is shifted 0.25 ppm, the H alpha-resonance -0.43 ppm, the H beta-resonance 0.03 ppm and the H gamma-resonance 0.09 ppm. In the serine residue the amide resonance is shifted 0.21 ppm, the H alpha-resonance -0.17 ppm, and the H beta-resonances 0.17 ppm.     

The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: a randomized pilot study

OBJECTIVE: To assess the long term effects of weight loss with and without additional aerobic and weight training exercises on exercise tolerance and cardiorespiratory fitness in obese women. EXPERIMENTAL DESIGN: Randomized prospective study for an approximately one-year community setting. PATIENTS: 31 healthy obese women volunteers (age 42.8 yrs +/- 6 SD) recruited by community advertisement. INTERVENTION: All subjects underwent a weight loss program consisting of low calorie diet and behavior therapy for a minimum of 46 weeks. They were randomly assigned to one of the four groups. Group A: diet alone, Group B: diet plus aerobic exercise program in a supervised group setting, Group C: Diet plus weight training and Group D: diet plus weight training plus aerobic exercise program. MEASURES: Exercise time (Tex) peak sustained workload (Wp), peak oxygen consumption (VO2), oxygen pulse and the rate of change of VO2 on recovery (VO2rec) were measured at the beginning and after 47.5 weeks +/- 1.5 SD, of the program. RESULTS: All subjects lost weight and achieved increased Tex and lowered resting VO2. VO2 peak and VO2 peak kg-1 increase in Groups B and D only. O2 pulse and VO2rec improved in group D. Improvements in exercise time correlated significantly with initial exercise time and weight loss. CONCLUSIONS: Weight loss increase Tex irrespective of participation in an exercise program. However, evidence of improved aerobic fitness occurred only in groups performing aerobic exercise.     

Prophylactic use of tropisetron or metoclopramide during adjuvant abdominal radiotherapy of seminoma stage I: a randomised, open trial in 23 patients

Human chorionic gonadotropin (hCG) is a glycoprotein composed of two subunits, alpha and beta, linked together by a covalent bond. Ectopic production of hCG has been described in various histological types of cancer. Actually, these malignant tumors predominantly secrete the free beta subunit (hCG beta) and not hCG. Production of free hCG beta is especially found in patients with bladder, pancreas, uterine and lung tumors. In patients with neuroendocrine tumors, serum levels of free hCG beta are higher in gastrointestinal-pancreatic and lung tumors. The significance of ectopic production of hCG beta--epiphenomena or intrinsic biological role--remains unknown. Several reports on the similar structure of hCG beta and certain growth factors suggest that free hCG beta could have an effect on cell proliferation. Increased serum levels of the free alpha subunit are found mainly in patients with neuroendocrine tumors localized in the gut or lung. Serum levels may also be raised in patients with a pituitary tumor, but such production is often associated with a rise in other pituitary hormones. The free alpha subunit plays a role in embryon development and would stimulate production of prolactin by decidual cells. The free alpha subunit may also play a role in tumor growth.     

Stage I non-Hodgkin''s lymphoma treated with doxorubicin-containing chemotherapy with or without radiotherapy

Assess the feasibility of proton MR spectroscopic imaging (1H-MRSI) of the striatum (putamen and caudate nucleus) in patients with Parkinson's disease and evaluate striatal neuronal density. Proton MRSI of the striatum and thalamus with 2 cc spatial resolution was performed in 10 patients with Parkinson's disease, 1 patient with atypical parkinsonism, and 13 control subjects. Single voxel proton MR spectra with signals from choline metabolites (Cho), creatine metabolites (Cr), and the putative neuronal marker, N-acetyl-aspartate (NAA), were obtained from the putamen and thalamus, but not the caudate nucleus, of patients with parkinsonism and control subjects. Metabolite rations in controls and patients were: in putamen NAA/Cho 1.70 +/- 0.25 vrs 1.74 +/- 0.32, NAA/Cr 2.80 +/- 0.79 vrs 2.36 +/- 0.42, Cho/Cr 1.63 +/- 0.25 vrs 1.39 +/- 0.3; in thalamus, NAA/Cho 1.78 +/- 0.15 vrs 1.62 +/- 0.22, NAA/Cr 2.78 +/- 0.34 vrs 2.64 +/- 0.41, Cho/Cr 1.57 +/- 0.25 vrs 1.65 +/- 0.28. There were no statistically significant differences between patients and controls. The putaminal NAA/Cho ratio of the single subject with atypical parkinsonism was lower than that of 9 of the 10 patients with classic Parkinson's disease and 11 of the 13 control subjects. Likewise, the putaminal NAA/Cr ratio in the single subject with atypical parkinsonism was lower than that of 7of the patients with guided selection of spectra from very small brain volumes, is a technique that can be used to evaluate neuronal density in individual subcortical gray nuclei in the brains of patients with parkinsonism. Using this technique, we have shown that Parkinson's disease produces no change in relative levels of the neuronal marker, NAA, in the putamen.     

Histologic factors affecting prognosis of pure seminoma of the testis

The histologic features of 92 cases of pure seminoma of the testis were reviewed in relation to the presence and degree of fibrosis, necrosis, granulomatous and lymphocytic reactions, interstitial cell hyperplasia, and lymphatic and/or vascular invasion associated with the primary tumor. No relationship between any of the histologic factors studied and survival was established.     

Short and long term results of pulmonary balloon valvuloplasty in children

Percutaneous balloon valvuloplasty is an alternative to surgical valvotomy for congenital pulmonary valve stenosis. Between 1985 and 1997, 73 valvuloplasties were performed in 70 patients, age range 1 day to 24.7 years. We reviewed the short- and long-term results in regard to transvalvular gradient and pulmonary insufficiency. The gradient was measured pre- and immediately post-valvuloplasty at catheterization and by Doppler echocardiography, and by echocardiography only at follow-up. Valvuloplasty was successful in 61/70 patients whereas surgical valvotomy was necessary in 9/70 because of a very dysplastic valve. A second valvuloplasty was performed in 3 patients presenting with restenosis. A 60% decrease in the gradient was noted immediately after the procedure, from 78.3 +/- 24.5 to 33.7 +/- 19.7 mm Hg (p < 0.05). A follow-up of more than 2 years (4.2 +/- 2.2 years) was obtained in 35 patients. A further decrease in the gradient was noted, to 20 +/- 12 mm Hg, and the degree of pulmonary insufficiency was mild in all patients except 2 with a moderate leak. The mortality was 0% and only 1 patient had a complication (endocarditis). The short- and long-term results of pulmonary percutaneous balloon valvuloplasty are excellent. It can be considered the therapy of choice. The gradient shows a further decrease during follow-up due to regression of the infundibular muscular stenosis. Failure is attributed to very dysplastic valves and these patients may require, in a second stage, a surgical approach (patch enlargement and/or valvulectomy).     

Pilonidal sinus: long term results of excision and closure technic. Review of the literature

The Authors report their experience in the surgical management of pilonidal sinus with modified Leichtling technique. Long term results of various treatments proposed in the past are analyzed: it is not possible to identify a satisfactory procedure for the treatment of pilonidal sinus. Ideal treatment should avoid hospital admission and general anaesthesia, assure a short time of healing, a reduced number of complications, a low risk of recurrence and a minimal time off from work. Authors' variations to the original technique show good results for non recurrent pilonidal sinus and a lower number of failed primary healing. Recurrences are probably related to the patient anatomical status which may be modified only by flattening natal cleft or surgically changing follicles orientation of presacral skin, together with a meticulous hygiene and shaving of the presacral healing area as well as a dietary regimen for obese patients.     

Acute angiographic and clinical results of long balloon percutaneous transluminal coronary angioplasty and adjuvant stenting for long narrowings

Historically, long coronary artery stenoses undergoing percutaneous transluminal coronary angioplasty (PTCA) are reported to have reduced procedural and clinical success in comparison with shorter lesions. The efficacy of long balloons (30 or 40 mm) in long lesions was evaluated. Eighty-two patients had 84 PTCA procedures with a primary long balloon. In all, 86 lesions were available for analysis. Data were collected prospectively on standard PTCA procedure forms. Coronary angiograms were reviewed and measured with digital calipers. Hospital charts were examined for complications. PTCA was performed in the left anterior descending artery in 44 cases (51%), the right coronary artery in 29 (34%) and the circumflex artery in 13 (15%). With the use of a modified classification system, 47 lesions (55%) were class C, 24 (28%) were class B2 and 15 (17%) were class B1. Mean lesion length was 22 +/- 11 mm (range 10 to 72), and 38 lesions (44%) were > or = 20 mm. Twelve patients received an intracoronary stent. The long balloon alone produced angiographic success (< 50% residual stenosis) in 77 lesions (90%). Angiographic success was achieved ultimately in all stenoses, using a stent in 7 patients and a short balloon in 2. There were 2 deaths (2%) and 1 Q-wave myocardial infarction (1%). One patient needed coronary artery bypass surgery. Clinical success without death, Q-wave infarction or bypass surgery was achieved in 83 of 86 procedures (97%). In conclusion, the use of long PTCA balloons with adjuvant stenting produced excellent results in these long stenoses. Lesion length was not a precursor of poor angiographic or clinical outcome.     

Adjuvant preoperative radiotherapy in patients with rectal carcinoma. Adverse effects during long term follow-up of two randomized trials

BACKGROUND: Adjuvant preoperative radiotherapy of patients with primary rectal carcinoma improves local control and survival, but also may increase the risk of early postoperative morbidity and mortality. In addition, the possible late adverse effects of this treatment are largely unknown. METHODS: The present study was based on 1027 curatively operated patients included in 2 prospective randomized trials of preoperative radiotherapy for rectal carcinoma patients (Stockholm I and Stockholm II Trials). The goal was to assess whether long term intercurrent morbidity and mortality were increased in patients allocated to the preoperative treatment. A computerized linkage of the randomized patients to a population-based registry of the Stockholm County Council was used to study hospital admissions for six groups of a priori defined diseases, putatively related to late adverse effects of the radiation. RESULTS: Preoperative radiotherapy significantly increased the incidence of venous thromboembolism (P = 0.01), femoral neck and pelvic fractures (P = 0.03), intestinal obstruction (P = 0.02), and postoperative fistulas (P = 0.01). For arterial disease and genitourinary tract diseases, no difference in risk was found between irradiated and non irradiated patients. Radiotherapy significantly reduced rectal carcinoma deaths in both trials and also improved overall survival in the Stockholm II trial. The late intercurrent mortality was similar in irradiated and nonirradiated patients. CONCLUSIONS: Although high dose, short term, preoperative radiotherapy can improve outcome after surgery for rectal carcinoma, there also may be an increased risk for long term morbidity. Refinement of the radiotherapy technique and a more accurate selection of patients suitable for the treatment will probably further improve the results, at least in regard to treatment-related complications.     

Successful treatment of a bulky seminoma in an abdominal undescended testis: a case report

An undescended testis is a major risk factor for the development of testicular malignancy. Herein we report the case of a 40-year-old man with a bulky seminoma arising in an uncorrected abdominal undescended testis. The definitive diagnosis was established by results of sonoguided biopsy and tumor marker studies. The patient was successfully treated with initial cisplatin and etoposide combination chemotherapy followed by resection of the residual tumor. The optimal diagnosis and treatment of this rare disease is discussed.     

Perforated peptic ulcer: a comparison of long term results following partial gastric resection or simple closure

The results of simple closure were compared with those of partial resection in the treatment of perforated peptic ulcer. The investigation was carried out 7-13 years after the primary operation on 126 patients who had been allotted to one of the two treatment methods on the basis of an almost randomized schedule. Better late results were obtained with partial resection than with simple closure in patients in the age range 50-59 years at operation, with short duration of perforation and with a long history of symptoms before perforation. None of the patients treated with partial resection later underwent surgical treatment for recurrence of symptoms. In the simple closure group 27.3 per cent needed further surgery at 3 months to 10 years after perforation.     

Morphologic studies on rats with adjuvant disease of long duration

Morphological studies were performed on Wistar-AF/Han-EMD-SPF-rats with adjuvant disease of 3 tp 14 months duration. Synovitis was observed in the noninjected paw up to the 6th month. While in the central bones resorption and new bone formation had ceased about the 7th month, periostal bone resorption proceeded until the 14the month. Morphological end results of the longlasting disease were pannus formation and fibrous ankylosis of the joints and severe sclerosis of the affected bones. Amyloid deposits were never observed.     

Prognostic factors in endometrial carcinoma: risk groups and adjuvant radiotherapy

Prognostic factors for disease-free survival in patients with endometrial carcinoma have been retrospectively assessed in 611 cases diagnosed, treated and followed at our institution between 1971 and 1990. Age, symptoms, comorbidity, FIGO clinical stage, and hysterectomy, as well as size and location of the tumor, histologic type, FIGO grade, myometrial invasion, lympho-vascular invasion, and final surgical stage have all been evaluated by univariate and multivariate methods. A mathematical predictive model has been applied to define risk groups, and the applied adjuvant treatments have been evaluated according to these groups. One hundred and thirty-one patients were not treated primarily with surgery, and the actuarial 5 and 10-year disease-free survival was 51.6% and 34.7% respectively. Only clinical stage (FIGO 1971) and modality of radiotherapy were significant prognostic factors. For the 480 patients treated primarily by surgery, independent prognostic factors for 5 and 10-year disease-free survival in multivariate analysis were extrauterine spread, absence of diagnostic comorbidity, FIGO grades 2-3, lympho-vascular invasion, age > 65 years and cervical extension. Five and 10-year disease-free survival was 81.5% and 73.4% respectively. Three risk groups were obtained, whose survival was not affected by the adjuvant treatments applied.     

Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center

Transport of presecretory proteins into mammalian microsomes involves a microsomal protein which is sensitive to photoaffinity labeling with 8-azido-ATP. Typically, protein folding within the lumen of the endoplasmic reticulum of mammalian cells depends on ATP and the member of the Hsp70 protein family, BiP. Here we addressed the question of whether protein transport into and folding within microsomes are differentially affected by photoaffinity labeling of microsomes with 8-azido-ATP. Folding of heterodimeric luciferase to the native state was more azido-ATP-sensitive compared to transport of the precursors of the two subunits. Therefore, we conclude that the microsomal protein which is responsible for the ATP-dependence of protein folding in the endoplasmic reticulum is sensitive to photoaffinity labeling with 8-azido-ATP and that this microsomal protein is distinct from the microsomal ATP-binding protein which is involved in protein transport.     

Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term control

The c-Jun N terminal kinases (JNKs) are members of the mitogen activated protein kinases family, which have been shown to be preferentially activated either by cytokines or stress stimuli. In this study we identify a selective and potent antisense oligonucleotide to RhoA (ISIS 17131) and investigate its effect on JNK activation induced by IL-1beta and H2O2 in A549 cells. The RhoA antisense oligonucleotide was able to inhibit JNK activation when A549 cells were stimulated by H2O2, but did not have any effect on IL-1beta induced JNK activation. Consistent with the idea that the phosphatidylinositol 3-kinase (PI 3-kinase) activates the small G protein exchange factors, H2O2 activated the PI 3-kinase. Additionally, Wortmannin, a potent inhibitor of the PI 3-kinase and phospholipase A2 (PLA2), and AACOCF3, also a PLA2 inhibitor, were able to inhibit JNK activation induced by H2O2, but they had no effect on JNK activation when stimulated by IL-1beta. These results suggest that, in A549, IL-1beta and H2O2 induce JNK activation by two independent pathways.     

Intravenous long term infusions of the rat without anesthesia

The lumbar-spine radiographs of 67 patients with idiopathic chondrocalcinosis articularis were reviewed for disc calcification and other changes. Calcification was present in 21 (31%) of the patients, seen most frequently at the L 2-3 disc space. The 21 patients as a group were significantly older than the 46 patients without disc calcification, and also had a much higher incidence of chondrocalcinosis in peripheral joints. There was no association with back pain or spinal stiffness. The 21 patients with disc calcification included six patients with a destructive peripheral arthropathy, and three of them had destructive changes affecting the lumbar spine. Three patients with a destructive peripheral arthropathy were also included in the group without disc calcification, and one of these had a destructive arthritis of the lumbar spine. For comparison, there was a 55% incidence of spinal chondrocalcinosis in nine patients with primary hyperparathyroidism and peripheral joint chondrocalcinosis, and a 6% incidence in 100 anteroposterior lumbar spine radiograph 'controls', taken before intravenous urography, although in this latter group the changes were minimal and confined to the margin of a single disc in each case.     

Core decompression for avascular necrosis of the distal femur: long term followup

Seventy-nine knees (45 patients) with a diagnosis of avascular necrosis of the distal femur treated between 1978 and 1989 were evaluated. All patients had a corticosteroid association (had been treated with >30 mg of prednisone for >2 weeks predating by at least 6 months the onset of avascular necrosis). Thirty-two knees were managed with protected weightbearing and rest. Core decompression was performed at a minimum of 3 months after the onset of symptoms in another 47 knees. The knees treated with protected weightbearing had an average asymptomatic period of only 11 months and all but 6 (18%) proceeded to total knee replacement within 6 years. Core decompression yielded good or excellent results in 73% of the knees at an average followup of 11 years (range, 4-16 years). Of the 13 knees with failed core decompression, 7 were asymptomatic for greater than 5 years. A subset of 26 knees from each group was matched for age, gender, diagnosis, Ficat and Arlet Stage, and length of followup. The matched noncore group had 23% survival as compared with 74% survival in the core group. This long term followup suggests that core decompression may slow the rate of symptomatic progression of avascular necrosis of the knee. In addition, core decompression may extend the symptom free interval in certain patients and may delay the need for more extensive procedures such as total knee arthroplasty.     

The results of radiotherapy for ependymomas: the Mayo Clinic experience

It is known that exogenous 11-cis-retinol inhibits the recovery of photosensitivity of bleached rod outer segments (ROS) and 11-cis-retinol exists in the interphotorecepter matrix. We examined the conversion of 11-cis-retinol with bovine ROS. ROS was incubated with 11-cis-retinol under dim red light. Retinoids were extracted from the reaction mixture with hexane and analyzed by HPLC coupled with a fluorescence spectrophotometer. Isomerization of 11-cis-retinol to all-trans-retinol was observed in the presence of ROS. This isomerization was not suppressed by heat treatment and did not have stereospecificity. In addition, we incubated purified rhodopsin and phospholipids extracted from ROS with 11-cis-retinol. Rhodopsin was found to isomerize 11-cis-retinol to all-trans-retinol as well as ROS, but phospholipids did not. In contrast, the phospholipids inhibited the isomerization of 11-cis-retinol to all-trans-retinol by the purified rhodopsin. Commercially available phospholipids, especially phosphatidylserine, also inhibited the isomerization. Our results suggest that rhodopsin has activity for the isomerization of 11-cis-retinol to all-trans-retinol and may play an important role in the detoxification of 11-cis-retinol in the ROS.     

Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients

BACKGROUND: Long term results after liver resection for hepatocellular carcinoma (HCC) are disappointing because the disease tends to recur. In this study, the authors assessed prognostic factors affecting long term outcome, in the hope that these factors might be used in selecting HCC patients for surgery. METHODS: During the period 1977-1995, 100 consecutive patients underwent curative liver resection; 78 of 100 had HCC arising on preexisting cirrhosis (53 Child's Class A and 25 Child's Class B). Thirty-five prognostic factors were evaluated for their association with overall survival (OS) and disease free survival (DFS) in univariate and multivariate analysis (Cox proportional hazards model). RESULTS: There were four postoperative deaths. Seven patients died in hospital of hepatorenal failure: six had Child's Class B cirrhosis and had undergone preoperative chemoembolization. Of the remaining 89 patients, 50 developed recurrence. All surviving Child's Class B patients had recurrence. Five-year OS, postoperative deaths included, was 38% (median, 36 months). Five-year DFS, postoperative deaths excluded, was 26% (median, 21 months). Independent prognostic factors for DFS were Child's class, glutamic-oxaloacetic transaminase, gamma-glutamyltransferase, alpha-fetoprotein, number of tumor nodules, width of resection margins, preoperative chemoembolization, and experience of the team that performed the surgery. Factors with an independent effect on OS were Child's class and width of resection margins. CONCLUSIONS: Liver resection can provide long term DFS in HCC patients with normal liver function. In patients with liver function impairment or an inadequate resection margin, recurrences are almost certain to occur. Preoperative chemoembolization significantly prolongs DFS but may increase the risk of postoperative liver failure in patients with liver function impairment.