Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment.

BACKGROUND: A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM. METHODS: This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival. RESULTS: A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009). CONCLUSION: A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.

Cytomegalovirus colitis in a critically ill patient following elective repair of an abdominal aortic aneurysm.

We describe a case of cytomegalovirus colitis in a critically ill but otherwise immunocompetent 61-year-old male. Infection was demonstrated by histology and confirmed by plasma polymerase chain reaction and detection of cytomegalovirus IgM antibody. The patient was treated with ganciclovir with resolution of the cytomegalovirus viraemia. Cytomegalovirus colitis may be an under-recognised problem in immunocompetent patients who are critically ill. Quantification of plasma cytomegalovirus DNA by polymerase chain reaction is a non-invasive method of supporting the diagnosis and can be used to monitor the treatment of cytomegalovirus infection in the immunocompetent.

Level of agreement and biopsy correlation using two- and three-tier systems to grade cervical dyskaryosis.

At present, a three-tier system is used to grade cervical dyskaryosis in the UK, although the two-tier Bethesda system is used in the United States, and the British Society for Clinical Cytology has recommended that a two-tier system be implemented here. In this study, we have retrospectively re-graded 117 conventional cervical smears using both systems to determine the intra- and interobserver variation and compare the cytology grading in both systems with the final histology. The intra and interobserver agreement was moderate using both grading systems, but the agreement between cytology grade and final histology was poor in both the two- and three-tier systems, and slightly worse using two-tier grading. However, when each of the three histological categories is considered separately the two-tier system appears to work better. Therefore, changing the way in which cervical dyskaryosis is graded in the UK may result in poorer agreement between the cervical smear result and the final histological diagnosis if introduced without proper training, monitoring and assessment.

Metastatic granulosa cell tumour of the diaphragm 15 years after the primary neoplasm.

We present the case of a female patient who complained of dyspnoea and was found to have a pleural effusion. A tumour involving the right diaphragm was seen on CT and after excision this was shown to be a recurrent granulosa cell tumour, 15 years after the original ovarian lesion had been treated by oophrectomy and radiotherapy. The case and literature relating to such a rare intra-thoracic metastatic tumour is discussed.

Early effects on the morphology of mouse small intestine of single or combined modality treatment with hyperthermia and X-irradiation.

This study describes the effects of hyperthermia and X-irradiation on the morphological appearance of normal, at risk tissues in the ileum of the mouse. The early morphological effects 1 day after a combined modality treatment are compared with those due to either hyperthermia or X-irradiation given alone. The response was assessed qualitatively and semiquantitatively using scanning electron microscopy and a villous scoring technique. Early post-irradiation effects on topography did not differ significantly from those observed after small intestine exteriorisation without treatment. The villous scores for the combined modality treatments reflected greater damage than would be expected from the sum of villous scores for each modality treatment on its own. This suggests that the combined modality treatment had a synergistic or enhancing effect. A 4 hour time interval between the two treatments did not seem to reduce the enhancing effect. Further studies are required to investigate the effects of fractionated combined treatment.

The use of electron microscopy and immunocytochemistry to characterise spontaneously-arising, transplantable rat tumors.

When examined by light microscopy, transplanted animal tumors frequently bear little resemblance to the original neoplasm. If such tumors are to be used as models of human cancer they should be characterised as regards extant rather than historical features. Consequently, we have examined, by electron microscopy and immunocytochemistry, five spontaneously arising tumors transplantable in the WAB/Not rat that are currently diagnosed on the basis of historical features only. A typical sarcoma was used for comparison. Of four spontaneously arising tumors previously classified as carcinoma, Sp4 possessed epithelial features on both ultrastructural and immunocytochemical analysis, Sp107 on ultrastructural analysis only and Sp15 and Sp22 by neither technique. Expression of vimentin was most marked with Sp15 and Sp107. The putative sarcoma, Sp24, showed clear evidence of epithelial differentiation but no evidence of vimentin expression. This study (a) records the phenotypic drift of experimental tumors on transplantation (most clearly with Sp107) and the co-expression of cytokeratins and vimentin in putative carcinomas, (b) confirms the inadequacy of routine histology for accurate characterisation of such tumors and (c) details techniques for a more thorough assessment of state of differentiation that should guide the choice of experimental model.

Mechanism of actinomycin D-induced resistance in Ridgway osteogenic sarcoma: an ultrastructural study.

The ultrastructural appearances of actinomycin D treated sensitive and resistant sublines of Ridgway osteogenic sarcoma (ROS) have been correlated with the suggested mechanism of drug-induced resistance. The resistant subline (designated ROS/ADX/G2) was developed by repeated suboptimal treatment of tumor bearing animals and passage of the fastest growing tumors. In the present experiments, animals bearing sensitive and resistant tumors were given a single intraperitoneal injection of actinomycin D (0.3 microgram/g) and examined at 1, 6 and 24 h after injection. The principal effect of actinomycin D treatment in both cell lines was the development of nucleolar segregation. This change, however, followed a different time-scale in each case, appearing more prominently at an early stage and returning more quickly to normal in the actinomycin D resistant cell line. These findings can be interpreted as being in agreement with the suggestion that reduced drug retention or an increased rate of detoxification provides the mechanism of acquired resistance.

Development of villous damage in mouse small intestine after local hyperthermia or irradiation.

Damage to mouse small intestine has been assessed in the period up to twenty-four hours after heating a portion of the gut for 20 min at 43 degrees C and also in the period up to nine days after 10 Gy/whole body X-irradiation. The surface changes and the light microscopic appearances after the two types of treatment were described. The damage was evaluated using scores produced by assessing villous collapse as seen with a scanning electron microscope (SEM). Maximum damage was seen two hours after hyperthermia and was more pronounced in antimesenteric portions of the same specimen. Maximum damage was observed three days after X-irradiation. Despite the difference in the time scale and severity of development of surface changes after the two types of treatment, the structure of the damaged and recovering villi looked similar, except for the apical extrusion of the enterocytes immediately following the heat treatment.

Structural changes in mouse small intestinal villi following lower body hyperthermia.

Heating an exteriorised loop of mouse small intestine resulted in marked changes in the shape of the villi as reported earlier. However, the exteriorisation techniques resulted in non-uniformity in both temperature and effect around circumference of intestine and, in addition, the extent to which handling contributed to the observed damage was not known. The work has therefore been extended using lower-body heating in the temperature range 37.5 degrees - 43.0 degrees C. Heating in the temperature range 37.5 degrees C to 41.0 degrees C produced minimal to moderate structural changes, manifested as scattered, vertically collapsed villi amongst predominantly "normal" villi. No villi showed conical or rudimentary forms of collapse. Such villi were, however, seen after heating at 41.5 degrees C and were greatly increased in number after heating at 42.0 degrees C. The most severe damage was observed after heating at 43.0 degrees C. Although the lower body heating method gave information which was less complicated by technical considerations, the hyperthermic damage observed was qualitatively similar to that previously seen following local administration of hyperthermia to an exteriorised loop of intestine. Direct quantitative comparisons between the two methods of heating are difficult because of differences in equilibration time and temperature. However, using a comparable heating time, less damage was scored following the exteriorisation technique compared with in situ heating.

Etched surfaces of plastic embedded and frozen hydrated gastrointestinal tissue.

Scanning electron microscopy (SEM) is most often used to describe the structure of natural surfaces, but it can also be used to examine surfaces created artificially by sectioning or cryofracture. When plasma etched resin sections are studied, the SEM combines some of the functions of a light microscope and a transmission electron microscope. When etched frozen hydrated tissue is examined the groundwork is laid for the use of X-ray microanalysis for the study of elemental concentrations in tissue unexposed to chemical agents of any kind. Examples are given of the study of jejunum and stomach with these two techniques. The results are integrated with data from conventional SEM images to produce composite diagrams which assist with the interpretation of function and topographical morphology.

Correlative scanning electron microscopy in gastrointestinal pathology.

Some applications of SEM to the study of gastrointestinal pathology are illustrated and discussed, along with a review of recent literature in this field. Particular emphasis is placed on correlative microscopy, involving, for example, the reprocessing of SEM specimens for LM and TEM, and of LM paraffin blocks for SEM. In terms of diagnosis and prognosis, the relevance of SEM data at present remains quite limited, calling for the further exploration of clinical and diagnostic problems through correlative techniques.