Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum

BACKGROUND: Colorectal cancer is the third most common cancer in the world, arising mostly from pre-existing adenomatous polyps (adenomas) of the large bowel. Patients with colorectal adenomas are at increased risk of colorectal cancer because of a high recurrence rate for adenomas. We followed a cohort of 1490 patients with rectal adenomas to determine whether recurrence might be related to pathologic characteristics of the initial adenomas. METHODS: The patients were identified in Haining County, China, from 1977 through 1978 by means of examination with a 15-cm rigid sigmoidoscope. They were followed by endoscopic examination at years 2, 4, 6, 11, and 16 after their initial polypectomy. New adenomas in the rectum were identified in 280 patients in these follow-up examinations. RESULTS: Statistically significant twofold to threefold elevated risks of metachronous (recurrent) adenomas were observed for patients who had more than two initial adenomas or whose most advanced initial adenoma was more than 1.0 cm in size, was of villous/tubulovillous type, or showed moderate to severe dysplasia. Much stronger associations were observed for advanced metachronous neoplasms, which are defined as cancers or adenomas with severe dysplasia, with multivariate adjusted relative risks (95% confidence interval) of 4.2 (1.8-9.9) for a large initial adenoma (>1.0 cm), 8.1 (4.2-15.6) for villous/tubulovillous architecture, and 14.4 (5.0-41.3) for severe dysplasia. In particular, patients who had a large (>1.0 cm) adenoma with severe dysplasia at baseline had a relative risk of 37 (7.8-174.7) of developing advanced metachronous neoplasms compared with patients who had small adenoma(s) with mild dysplasia. CONCLUSIONS: The risk of metachronous adenomas is closely related to the pathology of initial adenomas, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.     

K-RAS-2 gene mutations as predictors of metachronous colorectal adenomas

BACKGROUND: Mutations of K-RAS-2 gene and tumour suppressor genes have been found in both colorectal adenomas and carcinomas. The aim of this study was to investigate the prognostic value of K-RAS-2 gene mutations found in initial colorectal adenomas for predicting the risk of metachronous adenomas. METHODS: Genomic DNA was extracted from formalin-fixed and paraffin-embedded adenomas larger than 5 mm in diameter removed at the initial total colonoscopy between 1980 and 1982. All patients underwent colonoscopic follow-up for at least 10 years. The sequence of exon 1 of the K-RAS-2 oncogene was amplified with the polymerase chain reaction technique and screened for mutation by single-strand conformation polymorphism analysis. All suspected mutations were confirmed by direct DNA sequencing. The predictive value of K-RAS-2 gene mutations for the risk of metachronous adenomas was assessed by chi-square testing and logistic regression analysis. RESULTS: Of 54 patients 39 (72%) were male and 15 (28%) female. At the time the initial adenoma was removed, 31 (57%) patients were younger than 60, whereas 23 (43%) were 60 years or older. Point mutations of the K-RAS-2 oncogene were found in the index adenomas of 15 (27.7%) patients. Mutations were found more frequently in large (> or = 20 mm) adenomas and in adenomas with severe dysplasia (P = 0.0011 and P = 0.0310, respectively). There were no significant associations between K-RAS-2 mutations and anatomic location, histologic type, or number of synchronous initial lesions. Mutations were found predominantly at codon 12 with transversions from GGT to GTT (57%), from GGT to GAT (36%), and from GGT to TTT (one patient). The single mutation found at codon 13 showed a transversion from GGC to GAC. There were significant associations between size (> or = 20 mm) and K-RAS-2 mutation of the initial adenomas and the size (> 5 mm) of metachronous adenomas (P = 0.0259 and P = 0.0265, respectively). However, multivariate analysis showed that K-RAS-2 mutations did not provide a significant additional contribution to the prognostic value of the size of the initial adenoma (odds ratio, 7.62; 95% confidence interval (CI), 1.68-34.48) and the amount of villous structure (odds ratio, 0.22; 95% CI, 0.05-0.90) it contained. CONCLUSIONS: Patients with large (> or = 20 mm) adenomas and adenomas with K-RAS-2 mutations found at the initial examination have a significantly higher risk of developing large (> 5 mm) metachronous adenomas during surveillance. Multivariate analysis of initial adenoma characteristics showed that the risk of metachronous colorectal adenomas can be adequately estimated by the size and the histologic type of the largest initial adenoma and that K-RAS-2 mutations are of secondary importance only. Further studies based on a larger series will have to identify the adenoma characteristics that will help to improve follow-up strategies.     

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.     

Predictors and consequences of early gains in child psychotherapy.

This study examined the predictors and consequences of early gains among children (n = 130) receiving psychotherapeutic treatment as usual for a variety of disorders. Classification tree analysis showed that not receiving Medicaid, plus receiving a medication consult, were associated with any early gain (i.e., reliable change on one or more clinical scales, with the early gain either remaining in the clinical range or moving to a subclinical level) within the first eight treatment sessions, but only Medicaid status predicted subclinical gains. Overall, patients showing a subclinical early gain showed better long-term improvement in treatment than those with no subclinical gain; patterns of change for those with and without any early gain were similar but with smaller differences between groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of early failure of fixation in the treatment of displaced subcapital hip fractures

Malignant hyperthermia is a rare complication in clinical anesthesia, especially associated with the administration of succinylcholine or inhalation anesthetics. A 19-year-old patient, suffering from traumatic mandible fracture, underwent open reduction under general anesthesia. Unfortunately, following administration of succinylcholine, he also suffered severe facial twitch and the first episode of hypercapnia. After adequate management, the symptoms subsided. However, two hours later, the hypercapnia recurred, combined with progressive elevation of body temperature. After administration of intravenous dantrolene 120 mg, the patient's condition became stable and the procedure was completed without sequelae. As the muscle contracture test is not available in Taiwan, the clinical grading scale is presented as an alternative diagnostic method for malignant hyperthermia.     

Sequential peritoneal lavage and early diagnosis of colon perforation

In order to determine the usefulness of the lavage white blood cell count as a diagnostic indicator of occult colon perforation, we subjected 20 mongrel dogs to sham laparotomy, isolated liver stab wound, or closed colon perforation and then performed sequential peritoneal lavage. The lavage white cell count rose steadily in those animals with colon perforations, and 100% of these animals had a positive lavage at six hours post-injury. After correction for the white cells shed intraperitoneally secondary to hemorrhage, the lavage white count of animals with liver wounds and of those with sham laparotomy failed to rise significantly during the period of observation. Gram stain of the lavage effluent as well as lavage amylase determination were not of diagnostic value. For solid viscus injury, lavage white cell count rises in proportion to organ hemorrhage; in hollow viscus perforation, lavage white cell count rises disproportionately and is higher than one would expect on the basis of the red cell count. We believe sequential peritoneal lavage white cell counts are of value in the diagnosis of occult colon perforation.     

Activating SRC mutation in a subset of advanced human colon cancers

The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.     

Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas

The transforming growth factor-beta (TGF-beta) type II receptor (RII) is a colon cancer suppressor gene that is inactivated by mutation in 90% of human colon cancers arising via the microsatellite instability (MSI) pathway of carcinogenesis. To determine the pathophysiological consequence of RII mutations, we have determined the timing of their onset among 22 MSI human colon adenomas of varying stages. No RII mutations were detected in any early MSI adenoma, including all those with simple tubular or villous histology. The earliest RII mutation detected was in a region of high-grade dysplasia but was absent from the surrounding simple adenoma. Six additional RII mutations were all found in highly progressed adenomas that contained regions of frankly invasive adenocarcinoma. These RII mutations were detected in both the advanced adenomas and their adjacent regions of carcinoma. RII mutation is a late event in MSI adenomas and correlates tightly with progression of these adenomas to cancer.     

Thyrotropin-secreting adenomas of the hypophysis

A 28-year-old married female developed histoid papules and nodules de novo over her face, extremities, back, buttocks and thighs. She had developed erythema nodosum leprosum lesions without any antileprosy treatment. Histopathology from a histoid nodule showed well defined nodular collections of plump, spindle-shaped histiocytes. A few globi were also seen with Ziehl Neelson staining. Leucocytoclastic vasculitis was present in the ENL lesion. The CD4:CD8 ratio was 1.5:1.     

Morphogenesis and development of superficial spreading tumor of the colon and rectum

The aim of this study was to clarify the morphogenesis and mechanism of a wide intramucosal extension of a superficial spreading (epithelial) tumor (SST; defined as an epithelial tumor with wide intramucosal spreading involving a diameter of 30 mm or more) in the colon and rectum. For this purpose favorable sites, histological components, and histological growth patterns were compared between 95 cases of SST (16 adenomas and 79 carcinomas) and 2356 non-SST cases, which served as controls. The frequency of SST was significantly higher in the cecum and rectum, and lower in the sigmoid colon when compared to the locations of the control. Among the SST cases, 82.3% of superficial spreading carcinoma (SSC) had an adenomatous component and 96.2% had a cytologically low-grade carcinoma (CAL). In intramucosal SSC, the adenomatous and/or CAL component was predominant, and the proportion of high-grade carcinoma (CAH) was significantly smaller in intramucosal SSC in comparison with the control group. In the mucosal spreading area of SST, 78.9% were tubulovillous in histological type and 86.3% showed a replacing growth pattern. These results indicate that an SST initially develops as an adenoma in at least 85.3% of cases and CAL in 14.7% cases at most; spreads superficially in the mucosa by a replacing growth mechanism that forms a tubulovillous and villous structure; and is affected by intestinal peristalsis less than non-SST.     

Predictors of early high school dropout: A test of five theories.

This study compared the adequacy of 5 theories to predict dropping out of high school before the 10th grade. These theories include full mediation by academic achievement and direct effects related to general deviance, deviant affiliation, family socialization, and structural strains. Nested latent variable models were used to test these theories on prospective data from an ethnically diverse urban sample. Poor academic achievement mediated the effect of all independent factors on school dropout, although general deviance, bonding to antisocial peers, and socioeconomic status also retained direct effects on dropping out. Therefore, none of the theories tested was fully adequate to explain the data, although partial support was obtained for each theory. Implications for prevention of early high school dropout are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultrastructural study of the early development of the sheep embryo

An ultrastructural study of the different stages of pre-implantation in sheep was carried out, analysing the changes brought about mainly in the morula and blastocyst stages. The analysis of the embryos obtained showed a series of common characteristics in all stages, most noticeable being the presence of a high number of vesicles distributed in a uniform way in the cytoplasm, and also the presence of numerous electron-dense mitochondria in many varied forms. The most important ultrastructural modifications took place at the 16-cell stage and affected, principally, the nucleus, which presented numerous condensations of chromatin distributed along the nucleoplasm. The nucleoli adopted a reticular morphology, abandoning the compact aspects presented in the previous stage. These changes might be involved in the synthesis of embryonic RNA, and, accordingly, in the activation of the genome of this species. These data indicate that this stage is critical to the embryonic development and might be related to the blockage produced in the development of cultivated sheep embryos at the point of transition from 8 to 16 cells. Nevertheless, it should be pointed out that the first signs of modifications in the aspect of the nucleus are observed at the four-cell stage, being characterized by the appearance of vacuolated areas in the nucleolus, indicating the first signs of embryonic nucleic activity, which would anticipate the main change in the control of the protein synthesis.     

Genetic alterations are frequent in APC but rare in the TGF-beta type II receptor gene in cancer in adenomas of the colon

Measurements of stable chromosomal aberrations by fluorescence in situ hybridisation (FISH)-chromosome painting has the potential to be used for dose reconstruction, years after exposure to ionising radiation. The method is, however, not yet fully standardised and validated. In particular, with respect to the limited lifespan of circulating T-lymphocytes, a level of uncertainty exists on the long-term persistence of stable aberrations. The main principles of the technique will be demonstrated. Based on results from the literature, the reliability and limitations are discussed.     

Spatial transpositions and the early development of search.

Examined early developments toward mastering spatial-transposition problems in 60 20-, 30-, and 42-mo-old children. Ss received 2 kinds of transpositions: (a) relevant transpositions, involving switching a cup containing an object with 1 of 2 other empty cups, and (b) irrelevant transpositions, involving switching 2 empty cups while leaving in place a 3rd cup containing the object. Ss performed well on irrelevant transpositions but had more trouble with relevant transpositions: Although they localized their searches to the transposed cups on those problems, they did not select the correct cup until 42 mo. The youngest Ss searched primarily at the initial hiding location. They also showed some sensitivity to movement information but did not coordinate that with the initial hiding information as the problems required. By 30 mo, Ss did coordinate the 2 kinds of information but still showed a strong tendency to go to the initial location. By 42 mo, that tendency had been brought sufficiently under control to permit correct responding. The general picture of the early development of search is one in which children initially acquire search patterns on an experimental basis and only gradually come to a more principled understanding of their logical significance. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Caring for the community: development of the advanced practice nurse role

The historical and contemporary impetus for research in nursing is presented in brief. The factors affecting research use in practice are numerous and complicated and include political, financial, ideological and professional spheres. Various strategies that may enhance research use in practice have been suggested and evaluated and these are discussed.     

Immunoreactive parathyroid hormone in early and advanced renal failure

Immunoreactive parathyroid hormone (iPTH) was measured in the serum of 20 patients with early renal failure (ERF) using three assays with different specificity. Half of these patients had elevated iPTH in one or more assays, up to twice the upper limit of normal. In contrast, 36 patients with a creatinine clearance below less than 20 ml/min had an 80% elevated iPTH, up to 5 times the upper limit of normal. The patients with ERF and elevated iPTH had a lower serum calcium but no higher serum phosphate than those with normal iPTH. The differences in iPTH in early and end-stage renal failure can be explained by known differences in metabolism of different PTH forms in uremia.     

Epilepsy in early development: the lesson from surgery for early intractable seizures

This report examines the impact on development and the problems involved in assessing development in very young children with early-onset intractable seizures, particularly infantile spasms. A review of studies on medically and surgically treated children with infantile spasms underscores the relationship between seizure control and developmental outcome. About 50% of children with markedly intractable infantile spasms attained seizure control and significant improvement in the use of nonverbal communication, a developmental measure that has been used in other populations of developmentally delayed children. With the exception of duration of illness, clinical measures of age of onset of infantile spasms, type of surgery, and side of surgery did not appear to be related to the postoperative change in nonverbal communication. The neuropathology findings of surgically treated children with infantile spasms suggest that the underlying pathology occurs early in brain development. In conclusion, the cumulative effect of uncontrolled seizures and the underlying pathology might impact the early development of children with intractable infantile spasms.