Nodal staging of colorectal carcinomas and sentinel nodes

This review surveys the staging systems used for the classification of colorectal carcinomas, including the TNM system, and focuses on the assessment of the nodal stage of the disease. It reviews the quantitative requirements for a regional metastatic work up, and some qualitative features of lymph nodes that may help in the selection of positive and negative lymph nodes. Identification of the sentinel lymph nodes (those lymph nodes that have direct drainage from the primary tumour site) is one such qualitative feature that is claimed to allow the upstaging of colorectal carcinomas via an oriented, enhanced pathological work up. Current evidence in favour of a change in the requisite of assessing as may lymph nodes as is possible, and concentrating the efforts on only a selected number of lymph nodes, is weak.     

Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging

To establish an optimal categorization of cancer deposits without lymph node structure (extranodal cancer deposits [EX]) in a prognostic staging system, we analyzed 1,027 cases in which patients underwent potentially curative surgery for advanced colorectal adenocarcinoma. EX was classified as vascular invasion-type (VAS) or non-VAS.A total of 512 foci of EX were identified in 205 patients (20.0%), with VAS and non-VAS found in 68 and 182 patients, respectively. The hazard ratio for patients with nodal involvement was 3.6 and for patients with VAS and non-VAS, 2.5 and 4.7, respectively. Based on multivariate analysis of these 3 parameters, only nodal involvement and non-VAS were significant prognosticators. By using the Akaike information criterion, N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and non-VAS were treated together as an N factor and VAS was treated as a T factor ("new categorization"). The clinical significance of the TNM grading system for colorectal cancer would be enhanced if we treat EX as a new categorization.     

大肠癌增殖细胞核抗原的表达与淋巴结转移关系

目的：探讨在在癌增殖细胞核抗原（ＰＣＮＡ）表达与淋巴结转移关系。方法：用免疫组织化学ＡＢＣ法研究１１９例大肠癌肿瘤组织内ＰＣＮＡ的表达。结果：肿瘤细胞ＰＣＮＡ阳性率较高的病例淋巴结转移率了较高，说明ＰＣＮＡ阳性率较高的肿瘤细胞生长速度较快，易发生淋巴结转移，预后较差。结论：肿瘤细胞ＰＣＮＡ的表达可以作为判断肿瘤预后的一个客观标志。     

The influence of body size on the ventilatory response to hypercapnia

The slope of ventilatory response to hypercapnia at rest was determined in 77 healthy male students by means of the CO2 rebreathing method. It was found that the hypercapnic ventilatory response slope (S) was significantly lower in the lean group with BMI (body mass index) below 19 than that in the normal group, while there were no significant correlation between S and body weight or height. These results indicate that sensitivity of hypercapnia in the lean subjects differed from that of normal and overweight subjects.     

One Step Nucleic Acid Amplification (OSNA) - a new method for lymph node staging in colorectal carcinomas

Background  

Accurate histopathological evaluation of resected lymph nodes (LN) is essential for the reliable staging of colorectal carcinomas (CRC). With conventional sectioning and staining techniques usually only parts of the LN are examined which might lead to incorrect tumor staging. A molecular method called OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the metastatic status of the complete LN and therefore improve staging.     

Problematic issues in the staging of endometrial,cervical and vulval carcinomas

The International Federation of Gynecology and Obstetrics (FIGO) staging of tumours of the uterine corpus, cervix and vulva was revised in 2009. The greatest impact of the revised staging was on carcinomas of the uterine corpus. Uterine sarcomas are now staged separately. Changes to the staging system for vulvar carcinomas largely reflect the significance of lymph node status. Only minor amendments have been introduced for cervical carcinomas, which remain the only gynaecological tumours to be staged clinically. These revisions, based on recent evidence, require careful, more detailed assessment of several histological parameters at each anatomical site. The present review deals with the evidence and rationale underpinning the revisions, and includes practical guidance on tumour staging. This covers the assessment and measurement of myoinvasion and evaluation of cervical, parametrial, serosal and vaginal involvement in carcinomas of the uterine corpus; the identification and accurate measurement of stromal invasion in cervical and vulvar carcinomas; the assessment of unusual variants of carcinoma at each of these sites; and the assessment of lymph node involvement.     

The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas.

AIM: To investigate the effect of different interventions on the inclusion of data items in the histopathology reports of resected colorectal carcinomas. STUDY POPULATION: 272 routine histopathology reports on colorectal carcinomas from the department of histopathology, Royal Hallamshire Hospital, Sheffield. METHODS: The presence or absence of 10 specific data items was recorded for each report. The reports were divided into five audit periods. In the initial period reports were generated using free text with no agreed guidelines. In period 2, text guidelines had been issued; in period 3, flow diagram guidelines had been issued; and in periods 4 and 5, template proformas were attached to each specimen request form. RESULTS: All interventions produced some increase in inclusion rate for some features, but only with the introduction of template proformas did these rates approach 100% for all data items. Inclusion rates were 100% for all items in all cases reported using a proforma. In the final audit period 96% of specimens were reported using proformas. CONCLUSIONS: Template proformas produce a high rate of inclusion of data items in reports of colorectal carcinoma resection specimens.     

Chromosomal imbalances in the colorectal carcinomas with microsatellite instability

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability, exist in the colorectal carcinomas. To clarify the relationship between chromosomal abnormalities and mismatch repair gene defects in colorectal carcinomas, we performed a chromosomal analysis on 39 colorectal carcinomas with high-microsatellite instability (MSI-H) and compared the results obtained with those of 20 right-sided microsatellite-stable (MSS) colorectal carcinomas. Chromosomal imbalances (CIs) in MSS colorectal carcinomas were more frequent than in MSI-H colon carcinomas by comparative genomic hybridization analysis (70% versus 31%, P = 0.004). The CI patterns of MSI-H and MSS carcinomas were different. Frequent CIs in MSI-H colon carcinomas were gains of 4q (15%) and 8q (8%), and losses of 9q (21%), 1p (18%), and 11q (18%). In contrast, frequent CIs in right-sided MSS colon carcinomas were gains of 8q (50%), 13q (35%), and 20q (25%), and losses of 18q (55%), 15q (35%), and 17p (30%). We compared the mutation status of 45 target genes and CIs in our MSI-H tumors. Among these 45 target genes, mutation of hRAD50, a member of the DNA repair genes, and FLJ11383 were significantly related to MSI-H colorectal carcinomas with CIs (P = 0.01 and P = 0.02, respectively). Our findings indicate that unique CIs were present in a subset of MSI-H colorectal carcinomas and that these CIs are related to the mutation of several target genes, especially of hRAD50.     

The influence of spleen size on the distribution of red cells and plasma

The red cell mass, splenic red cell pool, and plasma volume have been measured in a series of 64 patients with splenomegaly due to haematological disorders. In 45 patients the total blood volume was increased, this being due to expansion of the plasma volume which was closely correlated with spleen size. There was no significant relationship between the red cell mass and spleen size but the splenic red cell pool increased with increasing spleen size. In 12 patients serial estimations were made whilst changes in spleen size occurred as a result of therapy or progression of the disease. The red cell mass did not alter but the splenic red cell pool showed a significant change from 8·9 ± 6·1% of the red cell mass at minimum spleen size to 17·5 ± 10·5% at maximum spleen size. There was progressive expansion of the plasma volume from 42·9 ± 5·0 ml/kg at minimum spleen size to 57·4 ± 15·3 ml/kg at maximum spleen size.     

Pathological features of colorectal carcinomas in MYH-associated polyposis

Aims:  MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics.
Methods and results:  Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status ( P  = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls ( P  = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls ( P  = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups.
Conclusions:  Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.     

The influence of activity on muscle size and protein turnover.

1. The effects of the loss of normal activity can be studied in muscles held in a shortened position by immobilizing the ankle in a plaster cast. Since the innervation remains intact with this procedure, removal of the restraining case allows normal activity to be restored. The soleus and plantaris muscles grew as a function of time after the return of normal activity and these changes in tissue size are explained by changes in the average rates of protein synthesis and protein break-down as measured by sensitive in vitro techniques. Activity stimulates protein synthesis and inhibits protein break-down of the soleus muscle, thus enabling the tissue to accumulate protein. Blockage of de novo synthesis of RNA, but not DNA, severely restricted the normal, rapid enhancement of protein synthesis after thr return of activity. 2. The return of isotonic activity to the extensor digitorum longus muscle after immobilization in a lengthened position failed to fully compensate for the loss of the growth-promoting influence of stretch and the tissue gradually returned to the size of the control muscle. During the recovery process the higher rate of protein turnover and RNA concentrations of the immobilized muscle returned to the lower values of the control.     

The influence of grid size on accuracy in radiotherapy dose plotting

The recent article by Niemierko and Goitein [Med. Phys. 16, 239-247 (1989)] illustrates well the errors which are occurring in plotting isodose lines. We wish to augment their analysis with similar work done at Cardiff a few years ago; to indicate some practical treatment outcomes they have omitted; to propose even more stringent requirements of the grid size used; and thus to further alert users and software manufacturers to this problem.     

The influence of spherulitic size on the environmental stress cracking of low density polyethylene

The influence of morphology in a low density, high melt index polyethylene was studied with particular reference to environmental stress cracking (ESC). Test samples of the polyethylene were molded under constant conditions, only the subsequent rate of cooling to room temperature being changed. Several techniques were used to study the resultant polymer including ESC tests, X-ray diffraction, optical microscopy and constant strain rate stress/strain tests. It was found that the faster the polymer was cooled after molding, the smaller was the typical diameter of the spherulites and the greater the resistance to stress cracking. A hypothesis is proposed to explain the differences in terms of the ease with which a crack can propagate, assuming that propagation is easier in amorphous material than within spherulites.     

The influence of selenium and selenoprotein gene variants on colorectal cancer risk

Colorectal cancer (CRC) is a major cause of mortality throughout the world and risk of CRC is known to be modulated by nutritional factors. Low intake of the micronutrient selenium (Se) has been implicated as a risk factor in CRC, and in this article we describe the biochemical functions of selenium in selenoproteins, review the evidence for an association of selenium status with CRC and adenoma risk and describe the genetic epidemiological data on selenoprotein genes and CRC risk. Epidemiological evidence linking Se intake to CRC risk is limited but there is strong evidence for a link to adenoma risk. Two studies show an association between a genetic variant in the selenoprotein S gene and CRC risk. Selenium intake modulates selenoprotein expression in the colon, especially selenoproteins W, H, M, 15 kDa selenoprotein and glutathione peroxidase 1, and downstream targets such as endoplasmic reticulum stress response, oxidative stress and inflammatory pathways. We hypothesis that Se, through the selenoproteins, plays a key role in the ability of colonic epithelial cells to respond to microbial and oxidative challenges and that a combination of low Se intake and SNP in selenoprotein genes can impair that role and so lead to increased risk of pre-neoplastic lesions. There is a need for both further studies of selenoprotein function in the colon and major genetic epidemiological and intervention studies.     

Morphologic and molecular events at the invading edge of colorectal carcinomas

The mechanisms whereby colorectal carcinomas invade the extracellular matrix remain elusive. In a series of studies on the growing edge of colorectal carcinomas, we found dilated neoplastic glands, some with a layer of flat tumor cells, and some lacking one or more groups of consecutive lining tumor cells (called glandular pores). Through the glandular pores, the retained glandular material was siphoned off directly into the juxtaposed extracellular matrix. The substances secreted by the tumor cells, rich in proteolytic enzymes, disrupted the anatomy of the extracellular matrix. To remodel the defective glands, the malignant cells, proliferating from the tip of the free borders of the pores, invade the enzymatically disrupted matrix to achieve glandular continuity. Sealing of these glandular flaws permits intraglandular accumulation of new proteolytic material, a mechanism that replicates a new wave of host invasion at the invading edge, thus ensuring stepwise but everlasting tumor progression in untreated patients. More recent findings indicated that the flat tumor cells at the advancing edge failed to express the proliferation marker Ki67 but overexpressed the mutated p53 protein. This paradoxic biologic behavior of tumor cells may be connected with the subsequent formation of glandular pores and strongly suggests that the arrested cell proliferation at the advancing tumor edge occurs independently of p53 mutation. Possibly, two independent molecular systems exist at the advancing edge of colonic carcinomas, one supervising cell proliferation and the other actively transferring the mutated p53 protein to daughter cells.