Biomedical subjects

Robert Rosenberg

Publications and source records attributed to Robert Rosenberg.

At least 19 recordsLinked to original sources

PubMed2026

NTRK-positive collision tumor of the gastrointestinal tract: a rare entity case report.

Neurotrophic receptor tyrosine kinase (NTRK) fusion-positive colorectal cancer (CRC) represents a rare molecular subset of CRC. We report an exceptional case of a collision tumor composed of two anatomically adjacent but histologically and genomically distinct primary colorectal carcinomas, each giving rise to a corresponding metastasis. Comprehensive histopathologic and molecular analyses demonstrated that one primary tumor and its matched metastasis consisted predominantly (> 90%) of a solid carcinoma harboring a TPR::NTRK fusion, high microsatellite instability (MSI-H), elevated tumor mutational burden (TMB), and loss of MLH1 and PMS2 expression by immunohistochemistry. In contrast, the second primary tumor and its corresponding metastasis exhibited conventional adenocarcinoma morphology with mucinous differentiation, lacked an NTRK fusion, and carried canonical driver mutations in KRAS, APC, SMAD4, and TP53. This case underscores the importance of integrated histopathologic and molecular evaluation in CRCs with heterogeneous morphology, as the identification of multiple, genomically distinct tumor components may have significant diagnostic, prognostic, and therapeutic implications.

NTRK gene fusion↗

PubMed2024

Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.

BACKGROUND: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery. METHODS: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored. DISCUSSION: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.

Genetic Association Studies↗

PubMed2007

Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer.

Aneuploidy and genetic instability are a hallmark of colorectal cancer and other solid tumors, and they are thought to enhance tumor progression. The gene MAD2L2 (mitotic arrest deficient 2-like 2) encodes the spindle checkpoint protein MAD2L2 (or MAD2B), a key component of a surveillance system that delays anaphase until all chromosomes are correctly oriented. Defects in this mitotic checkpoint are known to contribute to genetic instability, i.e., numerical and structural aberrations of chromosomes. We have previously identified MAD2L2 as significantly upregulated in locally restricted colorectal tumors by gene expression profiling. So far, MAD2L2 has not been reported to play a major role in human cancer in contrast to its homologue MAD2. To address this question, 118 histologically confirmed colorectal lesions were analyzed by quantitative real-time PCR for expression of MAD2L2, and compared to normal colon tissue from 11 patients. Twenty-five out of 118 tumor samples (21%) showed MAD2L2 overexpression of 3-fold or more compared to normal colon, and the fraction of overexpressing tumors increased with tumor stage. Correspondingly, protein levels of MAD2L2 were found to be significantly upregulated in tumors as compared to matched normal tissue. Tumors with upregulated MAD2L2 expression had significantly higher numbers of aberrant mitotic figures (anaphase bridges), an indication of chromosomal instability. Elevated expression of MAD2L2 was significantly correlated with reduced patient survival. By multivariate analysis, MAD2L2 expression was retained as an independent prognostic parameter for patient survival. Thus, our results demonstrate that overexpression of MAD2L2 correlates with bad prognosis in colorectal cancer.

Colon↗

PubMed2007

Trends in time to completion of mammographic screening and follow-up services.

OBJECTIVE: The popular press has raised questions about mammographic capacity in the United States, but mammographic utilization data have not been used to inform these concerns. We used data for the period 1995-2002 from the New Mexico Mammography Project to assess trends in time to completion of mammographic screening and follow-up services. CONCLUSION: The median time to return mammographic screening changed little over time, but trends in the time required to complete recommended follow-up services varied by type of service and urban or rural residence. Further monitoring of time required to complete screening and follow-up services in other regions can inform debates on mammographic capacity.

Breast Neoplasms↗

PubMed2006

PET imaging with [18F]3'-deoxy-3'-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer.

PURPOSE: Positron emission tomography (PET) using 18F-labelled 3'-deoxy-3'-fluorothymidine (FLT) was assessed for therapy monitoring in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. METHODS: Ten patients with locally advanced rectal cancer were included and underwent long-course preoperative chemoradiotherapy (total dose 45 Gy, 1.8 Gy/day, concomitant 250 mg/m2 5-fluorouracil) followed by surgery. FLT-PET was performed prior to chemoradiotherapy, 2 weeks after initiation of chemoradiotherapy and preoperatively (3-4 weeks post chemoradiotherapy). FLT uptake was correlated with histopathological tumour regression and changes in T stage. RESULTS: Mean tumour FLT uptake was 4.2+/-1.0 SUV before therapy and decreased significantly to 2.9+/-0.6 SUV 14 days after initiation of chemoradiotherapy (-28.6%+/-10.7%, p=0.005). The preoperative scan showed a further decrease to 1.9+/-0.4 SUV (-54.7%+/-7.6%, p=0.005). However, the degree of change in FLT uptake 2 weeks after initiation and after completion of neoadjuvant therapy did not correlate with histopathological tumour regression. CONCLUSION: FLT-PET did not seem to be a promising method for assessment of tumour response in the studied chemoradiotherapy regimen in patients with rectal cancer.

Adult↗

PubMed2006

Prospective breast cancer risk prediction model for women undergoing screening mammography.

BACKGROUND: Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors, including breast density and use of hormone therapy. We used prospective risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography. METHODS: There were 2,392,998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the preceding 5 years. Within 1 year of the screening mammogram, 11,638 women were diagnosed with breast cancer. Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent (P<.0001) criterion for the inclusion of risk factors. Risk models were constructed with 75% of the data and validated with the remaining 25%. Concordance of the predicted with the observed outcomes was assessed by a concordance (c) statistic after logistic regression model fit. All statistical tests were two-sided. RESULTS: Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age, breast density, family history of breast cancer, and a prior breast procedure. For postmenopausal women, the statistically significant factors included age, breast density, race, ethnicity, family history of breast cancer, a prior breast procedure, body mass index, natural menopause, hormone therapy, and a prior false-positive mammogram. The model may identify high-risk women better than the Gail model, although predictive accuracy was only moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to 0.644) for premenopausal women and 0.624 (95% CI = 0.619 to 0.630) for postmenopausal women. CONCLUSION: Breast density is a strong additional risk factor for breast cancer, although it is unknown whether reduction in breast density would reduce risk. Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance.

Adult↗

PubMed2006

Can Medicare billing claims data be used to assess mammography utilization among women ages 65 and older?

BACKGROUND: Medicare data may be a useful source for determining the utilization of mammography among elderly women, but the accuracy of these data has not been established. OBJECTIVE: We determined whether Medicare physician billing claims are an accurate reflection of mammography utilization among women ages 65 and older and whether they can be used to assess the use of screening as compared with diagnostic mammography. DATA SOURCES: Mammography use was assessed using Medicare billing claims and radiology reports from 2 mammography registries; the San Francisco Mammography Registry and the New Mexico Mammography Registry. METHODS: Completeness of the Medicare data was assessed by comparing mammography use based on Medicare, with radiology reports from the mammography registries, which served as the referent standard. Capture rates for Medicare claims for individual mammograms were examined, and women were characterized as having undergone at least 1 mammogram within each 2-year period based on the Medicare data, and these rates were compared with the referent standard. To determine whether Medicare data can distinguish between screening and diagnostic mammography, we performed a classification analysis using the mammography registries screening/diagnostic designation as the referent standard (dependent variable) and Medicare claim information as the independent/predictor variable. On the basis of the mammogram level classification analysis, women were categorized as having been frequently screened (at least 2 screening mammograms spaced by 12 to 36 months), screened (at least 1 screening mammogram), or not screened. SUBJECTS: Women ages 65 and older, diagnosed with breast cancer between 1992-1999, who had at least 1 mammogram between 1992-1999 were examined. RESULTS: A total of 3340 mammograms were obtained in 1371 women between 1992 and 1999. Overall, 83% of mammograms obtained by these women had a corresponding billing claim in Medicare. This increased from 65% in 1992 to 90% in 1999. Of women who underwent at least 1 mammogram during each 2-year period per the referent standard, 94% of women were accurately classified by Medicare claims as also having undergone mammography during the same 2-year period. In multivariable analysis, a mammogram was more likely to be associated with a billing claim over time, for women 80 years or older, and for white and Asian as compared with Hispanic women. Neither socioeconomic status nor screening/diagnostic designation affected the likelihood that a mammogram would be associated with a billing claim. The Medicare data accurately categorized a given mammogram as screening or diagnostic for 87.5% of mammograms. Lastly, there was moderate to substantial agreement in the categorization of women as frequently screened, screened or not screened between the 2 data sets (weighted kappa 0.74, 95% confidence interval 0.70-0.78). CONCLUSION: Medicare administrative claims are reliable for assessment of mammography utilization and have become more accurate over time. Medicare claims data also provide a mechanism for designating mammography as screening or diagnostic, which subsequently may allow accurate description of a woman's screening history.

Age Distribution↗

PubMed2006

Optimization of 3-dimensional imaging of the breast region with 3-dimensional laser scanners.

The anatomic conditions of the female breast require imaging the breast region 3-dimensionally in a normal standing position for quality assurance and for surgery planning or surgery simulation. The goal of this work was to optimize the imaging technology for the mammary region with a 3-dimensional (3D) laser scanner, to evaluate the precision and accuracy of the method, and to allow optimum data reproducibility. Avoiding the influence of biotic factors, such as mobility, we tested the most favorable imaging technology on dummy models for scanner-related factors such as the scanner position in comparison with the torso and the number of scanners and single shots. The influence of different factors of the breast region, such as different breast shapes or premarking of anatomic landmarks, was also first investigated on dummies. The findings from the dummy models were then compared with investigations on test persons, and the accuracy of measurements on the virtual models was compared with a coincidence analysis of the manually measured values. The best precision and accuracy of breast region measurements were achieved when landmarks were marked before taking the shots and when shots at 30 degrees left and 30 degrees right, relative to the sagittal line, were taken with 2 connected scanners mounted with a +10-degree upward angle. However, the precision of the measurements on test persons was significantly lower than those measured on dummies. Our findings show that the correct settings for 3D imaging of the breast region with a laser scanner can achieve an acceptable degree of accuracy and reproducibility.

Breast↗

PubMed2006

Impact of disseminated tumor cells in gastrointestinal cancer.

The detection of epithelial cells by sensitive immunological and molecular methods in blood, lymph nodes or bone marrow of gastrointestinal cancer patients may open a new approach to clinical metastasis research. The phenotypic and genomic characterization of these cells is of great value in the prediction of the further course of the disease and the monitoring of response to treatment. In addition, the role of ultrastaging in blood, lymph nodes and bone marrow of cancer patients for the indication of multimodal therapy is discussed in this review. The impact of prognostic or predictive factors for new treatment protocols in patients with gastrointestinal cancer was evaluated as well as the correlation with clinical factors.

Epithelial Cells↗

PubMed2005

Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors-correlation to tumor histopathology and clinical follow-up.

AIM: Evaluation of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) mRNA levels in formalin-fixed, and paraffin-embedded tissues of patients with colorectal cancer and their prognostic and/or predictive value. MATERIALS AND METHODS: Total RNA was isolated from microdissected, formalin-fixed, and paraffin-embedded tissues (controls and tumor) and subjected to quantitative RT-PCR (QRT-PCR) in the LightCycler system. Resulting mRNA levels correlated to tumor histology (n=102) and the clinical follow-up in patients treated by resection alone (n=40) and by resection plus adjuvant 5-FU-based chemotherapy (n=52). RESULTS: Correlation to histopathological parameters revealed a significant association between tumor stage and the TP mRNA level (T and N category and UICC) as well as the TP:DPD (T and N category and UICC) and TS:DPD (T category) ratio. In addition, tumor differentiation was correlated to the TS mRNA level and the TS:DPD ratio. Finally, the TS:DPD ratio was a prognostic marker for overall survival in patients receiving resection alone (p=0.032). Moreover, a high TP:DPD ratio (>8.1; p=0.002) and, marginally, low DPD (<8.2; p=0.05) mRNA levels significantly correlated to disease-free survival. CONCLUSION: We present a novel, standardized approach for TP, DPD, and TS mRNA quantification in archival tissue specimens and applied this to a large series of primary colorectal tumors. Correlations to histopathological parameters and clinical follow-up revealed an association of TP, DPD and TS mRNA expression patterns with tumor stage and suggested new prognostic and predictive markers for patients with colorectal cancer.

Aged↗

PubMed2005

Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression.

BACKGROUND AND AIMS: Colorectal cancer is one of the leading causes of cancer deaths in the Western world. A better understanding of the development and progression of colorectal carcinoma is needed to define novel targets and strategies for treatment. PATIENTS/METHODS: Gene expression profiles were determined for primary tumors of 10 locally restricted (T3N0M0), 8 lymphatically metastasized (T3N+M0), 7 systemically metastasized (T3N+M1) colorectal carcinomas, and 6 specimens of normal colorectal tissue by histology-guided oligonucleotide microarray analysis. RESULTS: A total of 1,995 genes were differently regulated in primary tumors of colorectal carcinoma compared with normal colorectal tissue. Besides common features of dedifferentiation and different expression of genes involved in cell division, cell adhesion, angiogenesis, signal transduction and metabolism we observed a deregulation of genes with an as yet unclear function. We identified 126 genes that were subsequently up- and 204 genes down-regulated during tumor progression. Furthermore, we found a cluster of five genes exclusively up-regulated in primary tumors of systemically metastasized colorectal carcinomas. A comparison of locally restricted (T3N0M0) and systemically metastasized (T3N+M1) primary tumors showed 50 deregulated genes with a massive down-regulation of immune-modulatory genes in primary tumors of systemically metastasized carcinomas. Primary tumors of lymphatically (T3N+M0) and systemically metastasized (T3N+M1) carcinomas differed in the expression of 19 genes. CONCLUSION: These results provide an additional step toward the identification of crucial genes for the progression of colorectal cancer and the identification of novel treatment targets or strategies.

Adult↗

PubMed2005

Prognostic impact of CK-20-positive cells in peripheral venous blood of patients with gastrointestinal carcinoma.

Despite curative tumor resection, about 30%-50% of patients with locally advanced gastrointestinal (GI) carcinoma develop tumor recurrence which may be caused by pre- or intraoperative tumor cell dissemination. We examined the combination of optimized density gradient centrifugation with a CK-20 reverse transcriptase-polymerase chain reaction to detect and quantify circulating tumor cells in peripheral blood. Peripheral venous blood (20 ml) of patients with GI carcinomas was collected during primary tumor staging before and after the endoscopy procedure. CK-20 expression in peripheral venous blood was found in 22 of 82 patients (26.8%) with a nonsignificant difference between the upper GI tract (23.9%) and the lower GI tract (30.5%). The correlation with clinical outcome (24-month-survival) revealed a significantly worse prognosis (p < 0.05) of CK-20-positive patients with carcinoma of the upper GI tract and a trend toward a worse prognosis for patients with carcinoma of the lower GI tract. Quantification of CK-20 expression in peripheral blood showed a significantly higher circulating CK-20 copy number (median: 2816) in patients with metastatic tumors than in those with non-metastatic tumors (median: 983) (p < 0.05). For a subset of 42 primarily operated patients, we correlated the detection rate with UICC (International Union Against Cancer) staging categories. In contrast to the upper GI tract, the detection rate of patients with carcinoma of the lower GI tract showed a trend toward tumor size (pT) and a significant correlation with the presence of distant metastases (pM) (p < 0.01) and the postoperative residual tumor status (R) (p < 0.01). The endoscopy procedure did not lead to an increased detection of CK-20 expression.

Adult↗

PubMed2005

Low vision standards.

Explore the source record for details and available documents.

Eyeglasses↗

PubMed2004

Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma.

PURPOSE: Maintenance of telomeres through reactivation of telomerase is a prerequisite for tumors to preserve their ability to proliferate. The purpose of this study was to evaluate telomere length and human telomerase reverse transcriptase (hTERT) expression as markers for progression and prognosis of colorectal carcinoma. PATIENTS AND METHODS: Telomere length and hTERT expression were analyzed in matched cancer and adjacent noncancer mucosa samples from 57 patients with R0-resected colorectal carcinoma. The median follow-up time was 76 months. RESULTS: Telomere length and hTERT expression correlated significantly in cancer tissues and adjacent mucosa samples (r = 0.52, P <.001; and r = 0.54, P <.001, respectively). Overall, cancer tissue had shorter telomeres than adjacent mucosa (P <.001). Only in noncancer tissue did telomere length decrease with age (r = 0.36; P <.01). Telomere length in cancer tissue was significantly correlated with tumor stage (P <.01), with longer telomeres in advanced tumors. Patients with ratios of telomere length in cancer to noncancer tissue greater than 0.90 had a significantly poorer overall survival compared with patients with smaller telomere length ratios (P <.002). In multivariate analysis, the telomere length ratio proved to be of independent prognostic value (P <.03). CONCLUSION: Telomeres in colorectal carcinoma tissue were significantly shorter compared with adjacent normal mucosa as an indication for extensive cell proliferation. The correlation with tumor stage and patient survival suggest that hTERT-mediated telomere stabilization may be critical for progression and prognosis of colorectal carcinoma.

Adult↗

PubMed2004

Effect of breast augmentation on the accuracy of mammography and cancer characteristics.

CONTEXT: Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. OBJECTIVE: To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. MAIN OUTCOME MEASURES: Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. RESULTS: Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval [CI], 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P =.008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P =.052) for women with breast augmentation vs without. CONCLUSIONS: Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.

Adult↗

PubMed2004

Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer.

BACKGROUND: The value of immunohistochemical detection of disseminated tumor cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer is still of uncertain prognostic value. We therefore evaluated the immunohistochemical detection rates and their prognostic value comparing three different monoclonal antibodies. METHODS: A total of 170 lymph nodes of 85 patients with curatively resected colorectal carcinoma at UICC stage I or II were evaluated for disseminated tumor cells. Frozen sections of each lymph node were immunohistochemically stained using three antibodies directed against CEA, CK20, and Ber-EP4. The detection rates were compared with histopathological tumor parameters and with the patient's survival. The median follow-up time was 86 months. RESULTS: CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were identified microscopically in lymph nodes of 23 patients (27%), 24 patients (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated tumor cells were found in consecutive sections and stained positive for all three monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with CEA-positive disseminated tumor cells was 72% compared to 91% of the patients without immunohistochemical evidence of tumor cells (p<0.01). While the identification of CK20-positive tumor cells was also correlated significantly with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed to reach significance (p=0.057). Multivariate analysis identified the tumor site (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive disseminated tumor cells (p<0.03) as independent prognostic factors. CONCLUSION: In colorectal carcinoma, the immunohistochemical detection of disseminated tumor cells in histopathologically pN0 peritumoral lymph nodes allows the identification of a subgroup with a significantly worse prognosis. Nevertheless, the prognostic value of immunohistochemically detected disseminated tumor cells remains controversial due to the nonuniform data in the literature.

Adult↗

PubMed2004

[Diagnostics and conservative treatment of anal incontinence].

Anal incontinence is diagnosed primarily by clinical and proctologic examination. Etiological factors of the disease are found in 85% of the patients by additional examinations. Motility dysfunction of colon and rectum has to be excluded (stenosis, dyschezia, internal hernias). Because anal incontinence is a multifactorial disease as a rule, the single compounds have to be diagnosed and have to undergo therapy. Accordingly, useful investigations are: endorectal ultrasound (defect of muscle, inflammatory or tumour infiltration), manometry (alteration of either anal resting pressure and/or anal squeezing pressure) and surface electromyography (ability of contraction, duration of contraction, strength). Neurophysiological examinations are: needle electromyography, pudendal nerve latency time measurement (PNLT). The occurrence of nerve damage determines the outcome of operative intervention! Conservative treatment is indicated in 80 to 90% of all patients, even higher when one includes all patients in the perioperative period. Possible therapy modalities are: nutrition consultation, physiotherapy, pelvic floor training, biofeedback training of pelvic floor and sphincter muscles, electrostimulation and the combination of both (EMG-triggered electrostimulation). Short-term results are satisfying in up to 85% of patients, but later, successful results depend on the patient's willingness or ability to continue training, and on his/her age.

Anal Canal↗

PubMed2003

Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography.

BACKGROUND: The relationships among breast density, age, and use of hormone replacement therapy (HRT) in breast cancer detection have not been fully evaluated. OBJECTIVE: To determine how breast density, age, and use of HRT individually and in combination affect the accuracy of screening mammography. DESIGN: Prospective cohort study. SETTING: 7 population-based mammography registries in North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California. PARTICIPANTS: 329 495 women 40 to 89 years of age who had 463 372 screening mammograms from 1996 to 1998; 2223 women received a diagnosis of breast cancer. MEASUREMENTS: Breast density, age, HRT use, rate of breast cancer occurrence, and sensitivity and specificity of screening mammography. RESULTS: Adjusted sensitivity ranged from 62.9% in women with extremely dense breasts to 87.0% in women with almost entirely fatty breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44 years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity increased from 89.1% in women with extremely dense breasts to 96.9% in women with almost entirely fatty breasts. In women who did not use HRT, adjusted specificity increased from 91.4% in women 40 to 44 years of age to 94.4% in women 80 to 89 years of age. In women who used HRT, adjusted specificity was about 91.7% for all ages. CONCLUSIONS: Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density.

Adipose Tissue↗