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Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium.

OBJECTIVES: We previously presented nomograms combining preoperative serum prostate-specific antigen (PSA), clinical (TNM) stage, and biopsy Gleason score to provide the likelihood of various final pathologic stages at radical retropubic prostatectomy. The data for the original nomograms were collected from men treated between 1982 and 1996. During the past 10 years, the stage at presentation has shifted, with more men presenting with Stage T1c, Gleason score 5 to 6, and serum PSA levels less than 10.0 ng/mL. In this work, we update the "Partin Tables" with a more contemporary cohort of men treated since 1994 and with revised PSA and Gleason categories. METHODS: Multinomial log-linear regression analysis was used to estimate the likelihood of organ-confined disease, extraprostatic extension, seminal vesicle or lymph nodal status from the preoperative PSA stratified as 0 to 2.5, 2.6 to 4.0, 4.1 to 6.0, 6.1 to 10.0, and greater than 10 ng/mL, clinical (AJCC-TNM, 1992) stage (T1c, T2a, T2b, or T2c), and biopsy Gleason score stratified as 2 to 4, 5 to 6, 3 + 4 = 7, 4 + 3 = 7, or 8 to 10 among 5079 men treated with prostatectomy (without neoadjuvant therapy) between 1994 and 2000 at Johns Hopkins Hospital. The average age was 58 years. RESULTS: In this cohort, more than 60% had T1c, more than 75% had Gleason score of 6, more than 70% had PSA greater than 2.5 and less than 10.0 ng/mL, and more than 60% had organ-confined disease. Nomograms of the robust estimated likelihoods and 95% confidence intervals were developed from 1000 bootstrap analyses. The probability of organ-confined disease improved across the groups, and further stratification of the Gleason score and PSA level allowed better differentiation of individual patients. CONCLUSIONS: These updated "Partin Tables" were generated to reflect the trends in presentation and pathologic stage for men newly diagnosed with clinically localized prostate cancer at our institution. Clinicians can use these nomograms to counsel individual patients and help them make important decisions regarding their disease.

Adult↗

Motivation to change drinking behavior: comparison of alcohol-dependent individuals in a general hospital and a general population sample.

The general hospital would be especially suited to initiate interventions if hospitalized alcohol-dependent individuals were particularly motivated to change their drinking behavior. This study compares the readiness to change of alcohol-dependent persons in the general hospital and the general population. Stages of change according to the model of Prochaska and DiClemente [6] are assessed using the Readiness to Change Questionnaire (RCQ) in two representative samples: 118 alcohol-dependent subjects admitted to a general hospital (sample 1) and 50 alcohol-dependent individuals in the general population (sample 2). In sample 1, alcohol-dependent persons were identified in 1167 consecutive admissions using screening questionnaires and a diagnostic interview (SCAN). In sample 2, alcohol dependence was assessed in 4075 individuals using a German version of CIDI. The distribution of stages of change differed significantly (p < 0.0001) between the groups, revealing a shift towards higher stages in the hospital subjects. Logistic regression analysis revealed that the stages of readiness to change and age contributed in predicting whether subjects belonged to the general hospital or the general population sample. Findings suggest that the general hospital is a suitable site to initiate interventions for alcohol-dependent individuals.

Adult↗

The rationale for adjuvant chemotherapy for high-risk prostate cancer.

PURPOSE OF REVIEW: With the advent of prostate-specific antigen, stage migration has resulted in a shift towards early-stage prostate cancer at diagnosis. Although radical prostatectomy and radical radiotherapy can be curative in organ-confined disease, there remains a significant proportion of early-stage patients who go on to develop progressive, incurable disease. This review will highlight developments in the identification of high-risk patients, and summarize the results of investigations of adjuvant chemotherapy in this setting. RECENT FINDINGS: The ability to identify patients at high risk of developing progressive disease is improving. Both preoperative and postoperative variables, as well as newer radiographic and molecular tools, can identify at-risk patients who may benefit from adjuvant therapy. Coupled with developments in chemotherapeutic agents for prostate cancer, this provides the rationale for investigating chemotherapy in this setting. Unfortunately, to date, reported trials involving adjuvant chemotherapy in prostate cancer are few, and generally involve small numbers of patients. Some of the studies confirm that certain populations of patients, such as those with node-positive disease, may benefit from systemic therapy. Definitive data, however, will be derived from ongoing randomized trials investigating adjuvant chemotherapy. SUMMARY: Although definitive data regarding systemic chemotherapy in adjuvant therapy are scarce, the results of the available studies, and the increasing accuracy in delineating the population at risk, have laid the foundation for future and ongoing studies in this area.

Biomarkers, Tumor↗

Internal water balance of barley under soil moisture stress.

Leaf water potential, leaf relative water content, and relative transpiration of barley were determined daily under greenhouse conditions at 3 growth stages: tillering to boot, boot to heading, and heading to maturity. The leaf moisture characteristic curve (relative water content versus leaf water potential) was the same for leaves of the same age growing in the same environment for the first 2 stages of growth, but shifted at the heading to maturity stage to higher leaf relative water content for a given leaf water potential. Growth chamber experiments showed that the leaf moisture characteristic curve was not the same for plants growing in different environments.Relative transpiration data indicated that barley stomates closed at a water potential of about -22 bars at the 3 stages studied.The water potential was measured for all the leaves on barley to determine the variation of water potential with leaf position. Leaf water potential increased basipetally with plant leaf position. In soil with a moisture content near field capacity a difference of about 16.5 bars was observed between the top and bottom leaves on the same plant, while in soil with a moisture content near the permanent wilting point the difference was only 5.6 bars between the same leaf positions.

Journal Article↗

Role of angiotensin II in activation of the JAK/STAT pathway induced by acute pressure overload in the rat heart.

This study was designed to determine whether the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway is activated in cardiac hypertrophy induced in vivo by pressure overload in rats and to demonstrate whether angiotensin II is involved in the activation of the JAK/STAT pathway. Acute pressure overload was produced by constricting the abdominal aorta of Wistar rats. Immunoprecipitation-Western blot analysis revealed that pressure overload activated JAK1, JAK2, and Tyk2 as early as 5 minutes and that STAT1, STAT2, and STAT3 were tyrosine-phosphorylated rapidly after exposure to the pressure overload. Phosphorylation of STAT1 and STAT2 peaked in the early stage at 5 to 15 minutes, whereas that of STAT3 peaked in the late stage at 60 minutes. Gel mobility shift of the interferon gamma activation site/interferon alpha-stimulating response element was observed immediately after the aortic banding, whereas the band of sis-inducing element was shifted in the late stage at 60 minutes. Both cilazapril (angiotensin II-converting enzyme inhibitor) and E4177 (angiotensin II type 1 [AT1] receptor antagonist) significantly suppressed the phosphorylation of Tyk2 and partially inhibited the phosphorylation of JAK2, but neither affected JAK1. Coimmunoprecipitation of the AT1 receptor with JAK2 or Tyk2 was clearly observed at 5 minutes and peaked at 15 minutes (20-fold the control value). These results indicate that the JAK/STAT pathway is activated by acute pressure overload in rats and that angiotensin II is involved in activating Tyk2, and partially activating JAK2, via the AT1 receptor. Both angiotensin II-dependent and -independent pathways take part in activating the JAK/STAT pathway in the pressure-overloaded rat heart.

Acute Disease↗

Early detection of prostate cancer with low PSA cut-off values leads to significant stage migration in radical prostatectomy specimens.

BACKGROUND: The introduction of prostate-specific antigen (PSA) contributed to a shift in tumor stage at diagnosis in patients with prostate cancer. The aim of the present study was to evaluate the effects of PSA screening with low PSA cut-off values on mean total and percent-free PSA levels in patients with prostate cancers at the time of diagnosis as well as on pathologic stage and mean Gleason scores in positive biopsies and radical prostatectomy specimens. METHODS: Data of 875 patients who were diagnosed with prostate cancers between 1996 and 2001 were analyzed. Patients were stratified into six groups according to the year of biopsy. Annual changes in total and percent-free PSA values, in Gleason scores of biopsies and radical prostatectomy specimens, and in pathologic stages of radical prostatectomy specimens were assessed. RESULTS: Mean PSA of patients diagnosed with prostate cancer decreased from 13.11 ng/ml (percent-free PSA: 11.89%) in 1996 to 7.33 ng/ml (percent-free PSA: 12.58%) in 2001 (P < 0.05). The percentage of organ-confined prostatectomy specimens increased from 64.3% in 1996 to 81.5% in 2001 (P < 0.05). However, mean Gleason scores increased from 5.23 to 6.33 over the 6 years (P < 0.05). The percentage of patients with biopsy-proven prostate cancers and PSA values below 4 ng/ml increased from 14.0% in 1996 to 39.2% in 2001. In the group with PSA values below 4 ng/ml organ-confined cancers were found in 80.0-95.2% of patients. CONCLUSIONS: PSAg screening with low cut-off levels has led to a significant reduction of mean baseline PSA levels in prostate cancer patients and to a significant increase in the percentage of organ-confined radical prostatectomy specimens, whereas mean Gleason scores have remained relatively constant.

Adult↗

Identification of a novel cardiac lineage-associated protein(cCLP-1): A candidate regulator of cardiogenesis.

We describe the isolation and characterization of a cDNA clone, called cCLP-1, that is a candidate for the previously described early cardiac-specific transcription factor BBF-1. BBF-1 binds the MEF2 (or element B) binding site within the cardiac myosin light chain 2 (MLC2) gene promoter. We used the element B sequence as a probe to screen an expression library constructed from mRNA obtained from the presumptive heart-forming regions of stage 6 chicken embryos. This yielded the cCLP-1 cDNA clone. Gel-shift analysis of stage 6 embryonic chicken protein extracts suggests that a protein that is recognized by the anti-cCLP-1 antibody binds to the same element B binding site to which BBF-1 binds. cCLP-1 mRNA was detected early in chicken development, prior to cardiac fate assignment at stage 4. The expression pattern of cCLP-1, based on whole mount in situ hybridization, coincides remarkably well with the established morphogenetic field of early heart formation. The nuclear localization of cCLP-1 is phosphorylation-dependent, suggesting that cCLP-1 may be a member of that class of transcription factors whose activity is regulated by cytoplasm to nucleus transport. Taken together, these data suggest that cCLP-1 may encode a novel transcription factor whose expression pattern is in agreement with that of the cardiogenic precursor cells of the early chicken embryo.

Amino Acid Sequence↗

Further observations on the site of bone prospective areas in the chick embryo wing bud.

The portion of the pre-axial region of the wing bud anterior to the cranial boundary of the skeletogenous territory of the stylo-zeugopod, according to Stark and Searls' recent maps, was surgically isolated in chicken embryos of the stages 18-25, and autoplastically grafted to the dorsal surface of the hind-limb bud or to the trunk. In other embryos of the same stages the cranial half or the cranial two thirds of the pre-axial region mentioned were isolated and heterotopically implanted. The experimental results consistently showed that the isolate contained a variously large portion of the presumptive radius and a significant part of the proximal half of the prospective humerus. In fact, the skeletal parts mentioned did not develop in situ in the donor wing while they differentiated, in general, in the implantation site. In this regard, the present research confirms data from previous experiments showing that Stark and Searls' maps do not offer an accurate representation of the position and the cranio-caudal width of the presumptive areas of the skeletal pieces of the wing. Our findings seem also to indicate that the major (or longitudinal) axis of the future radius is arranged along the proximodistal axis of the wing bud throughout the developmental stages mentioned; instead, the major axis of the future humerus undergoes a gradual shift, being first (stages 18-20) arranged nearly parallel to the bud base and getting more and more parallel to the proximo-distal axis of the wing bud through stages 21-24. Besides, between stage 18 and 25 the cranio-caudal width of the presumptive skeletogenous territory of the zeugopod, and to a lesser extent of the stylopod, seems to undergo a slight relative reduction with respect to the cranio-caudal thickness of the whole wing bud; this might depend on a process of aggregation of the prospective skeletogenous cells into gradually denser and more defined precartilaginous blastemes.

Animals↗

Staging and IgA VCA titre in patients with nasopharyngeal carcinoma: changes over a 12-year period.

The distributions of 2093 patients with nasopharyngeal carcinoma (NPC), by stage, over a 12-year-period did not show any evidence of a shift towards early stages despite growing awareness of this prevalent malignancy. The IgA VCA titre was determined for 1880 of these patients. The median titre increased from 40 in stage I to 80 in stages II, III, and IV, before rising to 160 in stage V. The percentage of patients with a titre > or = 320 increased steadily with advancing stages. Within the same disease stage, the percentage of patients having a particular titre value and the median titre varied considerably from year to year. Better education of the general population and a better serological marker for screening are needed for the early detection of NPC.

Antibodies, Neoplasm↗

Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder.

Forty patients with obsessive-compulsive disorder (OCD) were compared to matched healthy controls on neuropsychological tests which are sensitive to frontal lobe dysfunction. On a computerized version of the Tower of London test of planning, the patients were no different from healthy controls in the accuracy of their solutions. However, when they made a mistake, they spent more time than the controls in generating alternative solutions or checking that the next move would be correct. The results suggest that OCD patients have a selective deficit in generating alternative strategies when they make a mistake. In a separate attentional set-shifting task, OCD patients were impaired in a simple discrimination learning task and showed a continuous cumulative increase in the number who failed at each stage of the task, including the crucial extradimensional set shifting stage. This suggests that OCD patients show deficits in both acquiring and maintaining cognitive sets. The cognitive deficits in OCD may be summarized as: (i) being easily distracted by other competing stimuli; (ii) excessive monitoring and checking of the response to ensure a mistake does not occur; and (iii) when a mistake does occur, being more rigid at setting aside the main goal and planning the necessary subgoals. Both studies support the evidence of fronto-striatal dysfunction in OCD and the results are discussed in terms of an impaired Supervisory Attentional System.

Adolescent↗

[The perforation complication in diverticulitis: the evolution of the surgical procedure].

The ideal treatment for perforative complication in diverticular disease of the colon is still now rather controversial. Fundamental remains the simple and practical classification of Hinchey for perforated diverticulitis, especially for a meaningful evaluation of different experience. Without a common reference classification the percentage differences in mortality are completely devoid of scientific value. From a "three-stage" procedure the preferences are shifted towards a "two-stage procedure", thanks to the improvement of anesthetic and surgical modern facilities. The Hartmann procedure, performed not earlier than 4-6 months is the experience of the authors, but the ultimate choice is conditioned by the degree of peritoneal contamination.

Adult↗

Monitoring the self-assembly of chitosan/glutaraldehyde/cysteamine/Au-colloid and the binding of human serum albumin with hesperidin.

A new method for monitoring, in real-time, the self-assembly of chitosan/glutaraldehyde/cysteamine (CGC) on the gold surface and the immobilization of Au-colloid on CGC membrane with piezoelectric quartz crystal impedance (PQCI) are firstly proposed. Cyclic voltammogram and electrochemical impedance spectroscopy were also use to investigate the formation of Au-colloid/CGC. The viscosity-average molecular weight of chitosan used was firstly estimated as 16.8 x 10(5) with piezoelectric quartz crystal (PQC) sensor. On the basis of the analysis of the multi-dimensional information provided by PQCI, two stages existed in chitosan drying course: the frequency shift of the first stage was controlled by viscoelastic of the liquid, while the total frequency shift was due to mass change. The cross-link ratio of glutaraldehyde with chitosan was about 0.13, while for glutaraldehyde with cysteamine was about 0.217. PQCI also showed that the Au-colloid immobilization is a first-order reaction, while the HSA immobilization is a sum of two exponential functions, e.g., adsorption and re-arrangement. The association of the immobilized HSA with the purified hesperidin was monitored, and the association constant was estimated as 3.42 ml mg(-1) by Scatchard analysis.

Biosensing Techniques↗

Major shifts in genomic activity accompany progression through different stages of the hair cycle.

Hair follicles display a unique pattern of cyclic growth and regression involving cell proliferation, differentiation and migration. The molecular details of these processes are largely unexplored. Global expression analyses on the basis of about 20,000 genes for each morphologically distinguishable stage of the hair cycle revealed unexpected complexities of and major temporal shifts in transcriptional programs involving about 13% of all genes. In particular, hundreds of genes characterise the pattern of genomic activity during regression and resting phases; selected genes can be used to monitor hair growth in mice. We demonstrate that temporal expression patterns predict gene expression domains within the hair follicle. Expression of insulin-like growth factor binding proteins and anti-angiogenic factors is associated with the regression phase of the hair cycle.

Angiogenesis Inducing Agents↗

Evidence for the existence of an unfolding intermediate of thyroglobulin during denaturation by guanidine hydrochloride.

The unfolding of bovine thyroglobulin (Tg) in guanidine hydrochloride (GuHCl) solution was studied by following the fluorescence and circular dichroism. With increasing GuHCl concentrations, the emission maximum of the intrinsic fluorescence clearly red-shifted in two stages. At concentrations of GuHCl less than 1.2 M or more than 1.6 M, the red shift showed a cooperative manner. At concentrations of GuHCl between 1.2 and 1.6 M, an unfolding intermediate was observed. It was further characterized by the increased binding of the fluorescence probe 1-anilinonaphthalene-8-sulfonic acid (ANS). No significant changes of the secondary structure were indicated by CD spectra at the concentrations of GuHCl between 1.2 and 1.6 M. The conformation of this state has properties similar to those of a molten globule state which may exist in the folding pathway of the protein. Further changes in fluorescence properties occurred at concentrations of denaturant higher than 1.6 M with a significant red shift of the emission maximum from 340 to 347 nm and a marked decrease in ANS binding. This in vitro study gave a clue to understand the biochemical mechanism for the occurrence of aggregation and molecular chaperone binding during Tg maturation in vivo.

Anilino Naphthalenesulfonates↗

LiCl inhibits the establishment of left-right asymmetry in larvae of the direct-developing echinoid Peronella japonica.

The effect of LiCl on the establishment of left-right (LR) asymmetry in larvae of the direct-developing echinoid Peronella japonica was investigated with special attention to the location of the amniotic opening and ciliary band pattern. The larvae of echinoids are LR symmetric, but shortly before metamorphosis the larval LR symmetry is lost as a result of the formation of an amniotic cavity (vestibule), part of the adult rudiment, on the left side of the body. P. japonica has been considered to be the only exception among the echinoids, because the amniotic cavity forms at the midline of the larval body. In the present study we discovered the following two different LR asymmetric traits in larvae of P. japonica: the opening of the amniotic cavity initially forms at the midline of the larval body but shifts to the left dorsal side, and a looped ciliary band that initially forms with LR symmetry becomes LR asymmetric as a result of the formation of a bulge on left dorsal side. The establishment of LR asymmetry in both the location of the amniotic opening and the change in the shape of the ciliary band was influenced by exposing embryos to LiCl. Quantitative analysis of the shift in amniotic opening showed that exposure of embryos to LiCl causes repression of leftward shifting of the amniotic opening in earlier stage larvae, and leftward or rightward shifting in later stage larvae. These findings suggest that LiCl is an effective means of impairing the establishment of LR asymmetry in sea urchin embryos.

Animals↗

Multidisciplinary treatment of colorectal cancer in New Zealand: survival rates from 1997-2002.

INTRODUCTION: The surgical and oncological treatment of colorectal cancer has undergone steady evolution over the last 20 years, however nationally derived survival figures have been disappointingly slow to improve. This study is an analysis of prospectively collected data (taken over a 6-year period) on the outcome of colorectal cancer management from a single university surgical unit in New Zealand. METHODS: A comprehensive dataset was prospectively collected on all patients seen with colorectal cancer by a single surgical team, and complete follow-up was obtained. Details of surgical and oncology treatment of the primary lesion and of any subsequent disease and treatment were recorded. Survival was analysed by clinical and pathological variables. RESULTS: Over 6 years, 244 new patients with a total of 263 primary colorectal cancers were seen.; 97% of these patients had an operation and 95% had the primary tumour resected. The mortality after elective operation was 0.5% (1/197) and 8% (3/39) after urgent or emergency surgery. After a median follow-up of 32 months, recurrence in the pelvis was apparent in 1 of 72 patients after curative resection of rectal cancer and 4 of 18 after palliative resection, thus giving a total pelvic recurrence rate of 6% at 30 months. The 5-year survival rate of all new patients seen with a rectal cancer was 58% and 56.5 % for patients with a colon cancer. CONCLUSIONS: A combination of low operative mortality rates, low local recurrence rates in rectal cancer, the increasing use of adjuvant therapies, and careful follow up to detect (and where possible resect) metastatic disease at an early stage is associated with good cancer-specific survival figures. However further improvement in survival will need a shift to earlier stage at diagnosis and more effective chemotherapy (both in the adjuvant setting and for advanced disease) if significant gains in survival are to be made.

Aged↗

Screening program for colorectal cancer: effect on stage distribution.

BACKGROUND: The prognosis of patients with colorectal cancer is related to stages of disease at the time of diagnosis. Ultimately, the goal of fecal occult blood test (FOBT) screening programs is to reduce colorectal cancer mortality. METHODS: We reviewed the medical records and pathology reports of all 60 Harvard Community Health Plan (HCHP) members who were diagnosed as having colorectal cancer during the 2 years after our FOBT screening program began. The stage distribution of these 60 cases were compared with that of 76 cases diagnosed at HCHP before the FOBT screening program was started. RESULTS: Eight of 60 colorectal cancers diagnosed after the FOBT screening program was begun (13%) were diagnosed as a result of a positive screening test (Group I). The remaining 52 cases (87%) were diagnosed as a result of symptoms, physical findings, and/or the presence of anemia (Group II). Three of 8 Group I colorectal cancers (38%) were stage A, as compared with 8 of 52 of Group II colorectal cancers (15%). None of the 8 Group I colorectal cancers was stage D (metastatic) at the time of diagnosis, as compared with 11 of 52 Group II colorectal cancers (21%). CONCLUSIONS: We observed a favorable shift in the stage distribution of colorectal cancers diagnosed at HCHP after the FOBT screening program began (p less than .05). The shift was not attributable only to FOBT screening. We believe that the educational components of the program were important to its effectiveness. Our results support continued use of FOBT at HCHP.

Boston↗