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Prognostic relevance of transforming growth factor alpha (TGF-alpha) and tumor necrosis factor alpha (TNF-alpha) detected in breast cancer tissues by immunohistochemistry.

The function of different growth factors in the development and progression of malignant tumors and the role of cytotoxic cytokines in the host response generated against neoplasms have been recently studied. Anti-TGF-alpha and anti-TNF-alpha monoclonal antibody families have been developed and characterized previously by our laboratory. Libraries of anti-TGF-alpha and anti-TNF-alpha monoclonal antibodies were selected for equal immunoreactivity both in native (frozen) and in formaldehyde fixed, paraffin embedded histological sections. No differences were found between native and fixed samples demonstrated in 10 cases in the present prospective study. Retrospective investigation was performed in 35 histopathological specimens of breast cancer patients detailed clinically and observed during 5 years after the surgical treatment. Correlation between TGF-alpha and/or TNF-alpha expression and clinical staging--TNM score, lymph node metastasis, tumor recurrence and survival time--was analyzed. According to our present study, the TGF-alpha positive patients had worse clinical prognosis than the TNF-alpha positive and double positive cases during long term observation.

Adult↗

Prognostic implications of p53 and bcl-2 expression in 108 women with stage two breast cancer.

BACKGROUND: The mortality and morbidity of patients with breast cancer can vary even between individuals with similar histological stage at diagnosis. Identification of those individuals with prognostically poorer tumours is an essential prerequisite in planning adjuvant therapies. Some prognostic indices of tumour size, grade, oestrogen receptor status and nodal status are well established. AIM: The aim of this study was to examine the prognostic role of information relating to proto-oncogene and tumour suppressor gene expression. METHODS: 108 women with stage II breast cancer were studied. Tumour expression of p53 and bcl-2 were scored and then correlated with recurrence and mortality. RESULTS: We have shown that individuals poorly expressing bcl-2 in their tumours have a poorer disease-free and overall survival than those who express bcl-2. When p53 was strongly expressed, it was associated with poorer disease-free and overall survival. CONCLUSION: The profiling of individual tumour genetic expression of proto-oncogenes may allow for more specific identification of patients at higher risk of recurrence in breast cancer.

Biomarkers, Tumor↗

Exercise and eating disorder symptoms among young females.

BACKGROUND: In various settings, eating disorder symptoms have been linked to physical activity. METHODS: A random sample of 726 females, aged 17-23 years, responded on a self-administered questionnaire. "High level exercisers" (HiEx) were defined as subjects exercising > or =6 sessions/week, > or =1 h/session. "Exercisers with obligatory attitudes" (ObEx) were those obtaining a result above the 95th percentile on a composite score of obligatory exercise items. These groups were compared to controls regarding composite scores of eating disorder symptoms and other symptoms. RESULTS: While HiEx did not, ObEx obtained a significant result at the p<0.001 level regarding the score for body image problems, recurrent weight-reducing attempts, bingeing and post-prandial impulses to vomit. ObEx was also associated with symptoms related to stress and in particular with a high level of general activity coupled with perfectionistic ambitions. CONCLUSIONS: Eating disorder symptoms in young females seem to be associated with obligatory attitudes to exercise rather than with exercise quantity.

Adolescent↗

The predictors of persistence of depression in primary care.

164 patients in primary care who were recognized as depressed by their physicians and started on antidepressants were interviewed at 1 and 4 months after initiation of treatment. Ten factors hypothesized to be related to persistence of depressive symptoms were entered into a multivariate analysis to determine predictors of persistence of affective symptoms. Patients with minor depression were significantly older, more likely to be married or cohabitating, more likely to have serious medical illness, and had significantly less comorbid panic disorder, recurrent depression and lower neuroticism scores compared to patients with major depression. Approximately half of the patients in this primary care sample with major depression and one-third of those with minor depression were still distressed at 4 months, although few met criteria for major depression. Severity of depression and high neuroticism scores were the best predictors of persistent depressive symptoms.

Adolescent↗

Molecular biomarker in prostate cancer: the role of CpG island hypermethylation.

CpG island hypermethylation may be one of the earliest somatic genome alterations to occur during the development of multiple cancers. Recently, aberrant methylation patterns for different tumors have been reported. We present a comprehensive review of the literature describing the role of CpG island hypermethylation of DNA from prostatic tissue and bodily fluids from men with prostate cancer. We reviewed the literature to evaluate CpG island hypermethylation in tissue and bodily fluids of men with primary and metastatic prostate cancer. Additionally, we reviewed the literature with respect to CpG island hypermethylation patterns in other urological malignancies. Using modern analytic methods, CpG island hypermethylation detection can be achieved. In men with prostate cancer, correlations between specific gene regulatory region hypermethylation analyses and Gleason score, pathologic stage and tumor recurrence have been demonstrated. CpG island hypermethylation may serve as a useful molecular biomarker for the detection and diagnosis of patients with prostate cancer.

CpG Islands↗

Dynamics of HER2 status in recurrent cervical cancer: Highlighting the clinical value of reassessment.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have emerged as a promising therapy, making accurate HER2 assessment important. We assessed HER2 expression in recurrent cervical cancer, examined clinicopathological factors associated with HER2 positivity at recurrence, and analyzed HER2 discordance between matched primary and recurrent tumors. METHODS: We retrospectively identified patients with recurrent cervical cancer treated at a single center between 2013 and 2024. HER2 immunohistochemistry was performed on recurrent and matched primary tumors and scored according to the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma. Tumors scoring 2+ or 3+ were classified as HER2-positive. Factors associated with HER2 positivity were analyzed by logistic regression. RESULTS: Among 118 patients, the HER2-positive rate in recurrent tumors was 15.3% (18/118). HER2 positivity was higher in endocervical adenocarcinoma than in squamous cell carcinoma (30.6% vs 8.6%, P&#xa0;=&#xa0;0.009). Adenocarcinoma (adjusted odds ratio [OR] 4.80; 95% confidence interval [CI], 1.60-15.66) and recurrence outside the prior radiotherapy field (adjusted OR 7.92; 95% CI, 1.68-77.86) were independently associated with HER2 positivity. Among the 72 matched pairs, HER2 discordance was observed in 7 (9.7%), including HER2 gain in 4 of 61 (6.6%) and HER2 loss in 3 of 11 (27.3%). Adenocarcinoma was the only factor associated with discordance (OR 10.33; 95% CI, 1.99-104.04). CONCLUSIONS: In recurrent cervical cancer, HER2 positivity was associated with endocervical adenocarcinoma and recurrence outside the prior radiotherapy field. Reassessing HER2 by re-biopsy at relapse may inform treatment selection in a subset of patients.

Humans↗

Anticonvulsant action and long-term effects of gabapentin in the immature brain.

The anticonvulsant action and the long-term effects on learning, memory and behavior of the new generation antiepileptic drug gabapentin (GBP) were investigated in immature animals. Kainic acid (KA) was administered to rats on postnatal day (P) 35. Animals were treated with GBP or saline from P36 to P75 and spontaneous seizure frequency was monitored. After tapering the drug, the rats were tested in the water maze and open field test. Brains were then analyzed for histological lesions. Animals treated with GBP following KA-induced status epilepticus had a reduced incidence of spontaneous recurrent seizures, a better pathology score, and less aggressiveness compared to saline-treated controls. Effectiveness of GBP on seizure threshold was tested using flurothyl inhalation in 10 separate age groups of animals ranging from the newborn period to adulthood. Furthermore, GBP plasma concentration peaks were determined in all age groups. At all ages, GBP pre-treated animals demonstrated a higher seizure threshold. Plasma GBP concentrations did not significantly change with age. These data suggest that acute administration of a single therapeutic dose of GBP increases the seizure threshold at all ages studied, while chronic treatment following the status reduces spontaneous seizure frequency and cell damage and has no long-term adverse consequences on cognitive processes during development.

Acetates↗

Effects of cognitive therapy, applied relaxation and nitrous oxide sedation. A five-year follow-up study of patients treated for dental fear.

Five years after completing a controlled, randomized treatment trial comparing the effect of nitrous oxide sedation (NO), cognitive therapy (CT), and applied relaxation (AR), all 62 patients who had participated were invited to a follow-up questionnaire study. Forty-three responded. All participants had been to the dentist during the follow-up period. Mean scores (s) on Corah's Dental Anxiety Scale (CDAS) and Symptom Checklist 90 Revised (SCL-90-R, a measure of general psychological distress) were 10.4 (4.1) and 0.35 (0.34), respectively. There were no between-group effects. Significant changes across the assessment phases (at enrollment, after treatment, and 5 years after) were found for both dental fear and general distress (CDAS: F = 137.8, P < 0.01; SCL-90-R: F = 12.5, P < 0.01). However, no significant changes between measures obtained after treatment and at follow-up emerged. Seven participants (3 from the NO group, 2 from the CT group, and 2 from the AR group) had CDAS scores above 14, indicating a recurrent or continual dental fear problem. The majority (81%) assessed the dental fear treatment received 5 years previously to have been useful for them. In conclusion, the favorable effects on dental fear and general psychological distress continued at 5-year follow-up for all treatment groups.

Adolescent↗

Incidence, location, and significance of periprostatic and periseminal vesicle lymph nodes in prostate cancer.

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.

Adenocarcinoma↗

Repair of pectus excavatum and carinatum deformities in 116 adults.

OBJECTIVE: To determine the feasibility of surgically correcting pectus excavatum and carinatum deformities in adult patients. SUMMARY BACKGROUND DATA: Although pectus chest deformities are common, many patients progress to adulthood without surgical repair and experience increasing symptoms. There are sparse published data regarding repair of pectus deformities in adults. METHODS: Since 1987, 116 patients over the age of 18 years with pectus excavatum (n = 104) or carinatum (n = 12) deformities underwent correction using a highly modified Ravitch repair, with a temporary internal support bar. The ages ranged from 19 to 53 years (mean 30.1). Eighty-six patients sought repair after reviewing information regarding pectus deformities available on the Internet. Each patient experienced dyspnea with mild exertion and decreased endurance; 84 had chest pain with activity; 75 had palpitations and/or tachycardia. Seven patients underwent repair for symptomatic recurrent deformities. The mean severity score (chest width divided by distance from sternum to spine) was 4.8. The sternal bar was removed from 101 patients 6 months after the repair without complications. RESULTS: Each of the patients with reduced endurance or dyspnea with mild exercise experienced marked improvement within 6 months. Chest discomfort was reduced in 82 of the 84 patients. Complications included pleural effusion (n = 7), pneumothorax (n = 2), pericarditis (n = 2), dislodged sternal bar (n = 3), and mildly hypertrophic scar (n = 12). Mean hospitalization was 2.9 days; mean blood loss was 122 mL. Pain was mild and of short duration (intravenous analgesics were used a mean of 2.1 days). There were no deaths. With a mean follow-up of 4.3 years, 109 of 113 respondents had a very good or excellent result. CONCLUSIONS: Although technically more difficult than in children, pectus deformities may be repaired in adults with low morbidity, short hospital stay, and very good physiologic and cosmetic results.

Adult↗

Successes and setbacks of the falls consultation: report on the first 150 patients.

OBJECTIVE: We report the results of a Falls Consultation. DESIGN: Data concerning the first 150 patients are reported. Each patient was assessed by a geriatrician, a neurologist, and a physiatrist, who visited him or her at home, and was reassessed by the same geriatrician 6 mo later. RESULTS: Of the 150 patients, 135 patients completed the initial evaluation. Most of them were frequent fallers. The population was very heterogeneous regarding the health status and the degree of disability. In most cases, falls were the result of several interacting factors. The most frequent recommendations from the staff were physical therapy, environmental changes, and medication changes. Over the following 6 mo, approximately one out of four patients had experienced new falls. However, the risk of falling was significantly reduced (5.3 +/- 7.3 falls in 6 mo before vs. 0.8 +/- 1.6 falls in 6 mo after the intervention). The Activities of Daily Living score was a predictor of recurrent falls, hospitalization, and institutionalization. CONCLUSION: Our results show that a multidisciplinary falls consultation can be efficient in reducing the risk of falls in nonselected elderly fallers but suggest that differential strategies are needed to manage adequately the more vigorous and the frail old person as well.

Accidental Falls↗

Long-term benzodiazepine use and cognitive decline in the elderly: the Epidemiology of Vascular Aging Study.

Several cross-sectional studies have found cognitive impairment in subjects taking benzodiazepines for long periods. However, it is not known whether long-term use of benzodiazepines accelerates cognitive decline in the elderly. The authors addressed this issue in a follow-up study of 1,389 people aged 60 to 70 years recruited from the electoral rolls of the city of Nantes (Epidemiology of Vascular Aging study). Data on cognitive functioning (five cognitive tests), depressive symptoms (Center for Epidemiologic Studies-Depression Scale), anxiety symptoms (Spielberger Inventory Scale), use of psychotropics and other drugs, and tobacco and alcohol consumption were collected at baseline, 2-year, and 4-year examinations. People reporting to take benzodiazepines at one, two and three examinations were classified as episodic, recurrent, and chronic users, respectively. Among the 1,176 subjects (85%) who participated in the three examinations, the proportions of episodic, recurrent, and chronic users were 10%, 6%, and 7%, respectively. Chronic users of benzodiazepines had a significantly higher risk of cognitive decline in the global cognitive test (Mini Mental State Examination) and the two attention tests than nonusers (Mini Mental State Examination: odds ratio [OR] [95% confidence interval (CI)] = 1.9 [1.0-3.5]; Digit Symbol Substitution test: OR [95% CI] = 2.7 [1.6-4.7]; Trail Making test, part B: OR [95% CI] = 2.1 [1.2-3.7]). Overall, episodic and recurrent users had lower cognitive scores than nonusers, but differences were not statistically significant. These results were independent of age, sex, education, alcohol and tobacco use, anxiety and depression scores, and use of psychotropic drugs other than benzodiazepines. The findings suggest that long-term use of benzodiazepines is risk factor of increased cognitive decline in the elderly.

Aged↗

Ligasure trademark vs conventional diathermy haemorrhoidectomy: long-term follow-up of a randomised clinical trial.

OBJECTIVE: Ligasure haemorrhoidectomy has short-term benefits over conventional diathermy haemorrhoidectomy. The current study aimed to determine the long-term efficacy of Ligasure haemorrhoidectomy. SUBJECTS AND METHODS: Forty patients, previously randomised to Ligasure or diathermy haemorrhoidectomy in 2002, were invited to participate in the study. Haemorrhoidal symptoms and patient satisfaction were recorded. Incontinence was quantified and sphincter anatomy and function assessed by endoanal ultrasound and anorectal manometry. RESULTS: Thirty (75%) patients participated in the study (14 Ligasure, 16 conventional). There was no difference in age, sex distribution, or length of follow-up (Ligasure : 37 months; conventional: 36 months) between the groups. Both techniques achieved good symptom control, but with a trend to less recurrent bleeding following Ligasure. Incontinence scores and patient satisfaction were similar. A significant difference was observed in internal sphincter thickness (Ligasure : 2.5 mm, 2.2-2.8 (mean, 95%CI) vs conventional: 1.88 mm, 1.7-2.1, P = 0.005) and rectal urge sensation (Ligasure : 284 mls, 211-378 vs conventional: 173 mls, 129-217, P = 0.08). CONCLUSION: Ligasure is as effective as conventional diathermy haemorrhoidectomy in achieving long-term symptom control. Less radical haemorrhoidal excision with the Ligasure could explain the differences in internal sphincter thickness and urge sensation, and might make it the preferred method for patients with compromised sphincter function.

Digestive System Surgical Procedures↗

Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas.

BACKGROUND: In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH) on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH) data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches. RESULTS: Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss. CONCLUSION: We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation of the PTEN gene in prostate carcinogenesis.

Chromosome Aberrations↗

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Adolescent↗

Atypical glandular cells of undetermined significance. Outcome predictions based on human papillomavirus testing.

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.

DNA, Viral↗

A comparison of rotation and nonrotation in tetracycline pleurodesis.

Previously, we have shown rapid and complete dispersion of tetracycline hydrochloride in the pleural space following chest tube instillation. To assess the clinical relevance of this observation, we randomized patients with symptomatic pleural effusions to rotation (R) (n = 19) and nonrotation (NR) (n = 21) groups following administration of tetracycline hydrochloride, 20 mg/kg (n = 30); 300 mg of minocycline hydrochloride (n = 6); and 500 mg of doxycycline hydrochloride (n = 4) through a chest tube. Patients in the R group were maneuvered through six positions for the 2 h that the chest tube remained clamped. The NR patients remained supine for 2 h. Rotation and nonrotation groups were similar in demographics, source of pleural effusion, symptoms, and serum and pleural fluid analyses (all p = NS). A chest radiograph was scored based on pleural fluid recurrence throughout survival or up to 12 months. Survival, duration of chest tube instillation, and success of pleurodesis assessed by radiographic pleural fluid reaccumulation (73.7 vs 61.9 percent; R vs NR) were similar (p = NS). Rotational maneuvers appear to offer no benefit to the success of pleural symphysis after intrapleural instillation of tetracycline class agents.

Aged↗

Postoperative nerve root displacement and scar tissue. A prospective cohort study with contrast-enhanced MR imaging one year after microdiscectomy.

PURPOSE: To investigate the association between postoperative nerve root displacement and epidural scar tissue. MATERIAL AND METHODS: One hundred patients who had undergone lumbar microdiscectomy were included in a prospective cohort study with a 1-year follow-up. The patients were classified as failures or successes at the 12-month follow-up according to a clinical score. Patients with signs of recurrent disc herniation on MR were excluded from the study. All the 13 patients classified as failures were investigated with MR at the 1-year follow-up, and 40 patients classified as successes were picked at random for MR imaging; thus MR was performed in 53 patients. The MR images were independently evaluated by two neuroradiologists. The images were rated according to the presence or absence of nerve root displacement at the surgically treated disc interspace. Scar formation was rated according to two different classification systems. RESULTS: Nerve root displacement was observed in 13 patients. No evidence of scar formation was found in 4 patients, a small amount in 11, intermediate in 37 and extensive scar formation in 1 patient. No association between nerve root displacement and the amount of scar tissue was found. CONCLUSION: Postoperative nerve root displacement seems to be an independent clinical entity not associated to postoperative scar tissue.

Adult↗