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Biomedical subjects

N J Carr

Publications and source records attributed to N J Carr.

At least 19 recordsLinked to original sources

Hyperplastic polyps of the duodenum: an unusual histological finding.

A 58-year-old man underwent upper gastrointestinal surveillance endoscopy for Barrett's oesophagus. This showed a possible gastric ulcer, although histological examination was normal. Follow-up endoscopy showed white ridges in the distal duodenum and these were subjected to biopsy. Histological examination of the biopsy specimens showed polypoid duodenal mucosa showing features similar to those of a hyperplastic polyp of the colon. In addition, the mucosal surface was focally of gastric surface type. The features were interpreted overall as most likely to represent an unusual form of regenerative change in the setting of previous chronic inflammatory mucosal damage. The case is presented as an unusual histological phenomenon at this site; it would be important not to overdiagnose neoplasia in this situation.

Barrett Esophagus↗

The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?

BACKGROUND: Mesorectal margin tumour involvement is a predictor of local recurrence in rectal carcinoma and an indication for postoperative radiotherapy in suitable patients. However, the prevalence of non-peritonealised surgical margin involvement in ascending colon carcinoma is unknown. AIMS: To test the hypothesis that retroperitoneal surgical margin (RSM) tumour involvement occurs in distal caecal and proximal ascending colon carcinoma. METHODS/RESULTS: One hundred right hemicolectomy specimens, removed for adenocarcinoma of the caecum or proximal ascending colon, were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The tumour distance from the RSM was recorded. RSM tumour involvement was present in seven cases (7%). Direct (non-nodal) RSM tumour involvement (five cases) only occurred in posterior or circumferential tumours. CONCLUSIONS: RSM tumour involvement occurs within a considerable number of distal caecal and proximal ascending colon carcinomas. The rate of RSM tumour involvement identified here is similar to a previously published local recurrence rate of 10% in caecal carcinoma, suggesting that RSM tumour involvement may be a predictor of recurrence in these tumours. Therefore, patients with distal caecal or proximal ascending colon carcinoma and RSM tumour involvement may benefit from postoperative radiotherapy.

Adenocarcinoma↗

Deficient alpha smooth muscle actin expression as a cause of intestinal pseudo-obstruction: fact or fiction?

AIMS: To test the hypothesis that deficient alpha smooth muscle actin (ASMA) expression in intestinal smooth muscle, as assessed by immunohistochemistry, is specifically associated with clinical evidence of intestinal pseudo-obstruction. METHODS: Seventeen archival, formalin fixed, paraffin wax embedded samples of small intestine and 12 samples of large intestine were studied. Two of the small bowel samples and one large bowel sample were from patients with symptoms of intestinal pseudo-obstruction. The controls were longitudinal surgical margins from hemicolectomies performed for carcinoma. Immunohistochemistry was performed using primary antibodies to ASMA, smooth muscle myosin heavy chain (SMMHC), and desmin. The relative intensities of immunohistochemical expression in the circular and longitudinal muscle layers of the muscularis propria were assessed in each sample, for all three markers. RESULTS: All samples showed strong SMMHC and desmin expression in the inner circular and outer longitudinal layers of the muscularis propria. Both small intestinal samples from the cases and 11 of 15 controls showed no or minimal ASMA expression in the inner circular layer, with the remaining four controls also showing ASMA labelling in this layer that was weaker than within the longitudinal muscle. In contrast, intense ASMA expression was seen in both muscle layers within the large intestine in the remaining case, and in the controls. CONCLUSIONS: There is insufficient evidence from this study to support the hypothesis that ASMA deficiency in intestinal smooth muscle, as determined by immunohistochemistry on archival tissues, is specifically associated with intestinal pseudo-obstruction.

Actins↗

Histopathological assessment of lymph nodes in colorectal carcinoma: does triple levelling detect significantly more metastases?

AIMS: Standard practice is to take one section from every lymph node found in colorectal carcinoma resection specimens, to look for metastatic carcinoma. This study evaluates whether assessing three sections separated by 100 microm detects significantly more metastases in nodes than the conventional single section. METHODS: A retrospective study of 100 colorectal carcinoma resection specimens. All blocks containing lymph nodes had two extra histological sections cut (separated by 100 microm) and stained with haematoxylin and eosin. The original slide was called level 1, and the extra two sections levels 2 and 3. RESULTS: Twenty Dukes's A (equivalent to WHO-UICC stage grouping I, pTNM stage pT1/2N0), 43 Dukes's B (equivalent to WHO-UICC stage grouping II, pTNM stage pT3/4N0), and 37 Dukes's C (equivalent to WHO-UICC stage grouping III, pTNM stage at least pN1) cases were examined (total 1453 nodes). Twelve extra metastases (in 11 patients) were discovered in nodes at levels 2 and 3, which were negative in level 1. Ten cases were Dukes's C and, in one patient, this led to upstaging from N1 to N2 (pTNM classification system). One case was Dukes's B and the discovery of a single metastasis on level 2 upstaged it to Dukes's C. CONCLUSIONS: Triple levelling detected more tumour deposits than the conventional single section. In two patients, the staging classification of the lesion was changed, with potentially important implications for prognosis and management.

Adenocarcinoma↗

Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract.

AIMS: The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms. METHODS AND RESULTS: Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7-. Well-differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7-/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high-grade neuroendocrine carcinomas were negative for both CK7 and CK20. CONCLUSIONS: Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.

Adenocarcinoma↗

Vascular resistance in human muscle flaps.

Important differences in free muscle flap survival have been reported in the setting of long arterial and venous vein grafts. The authors provide insight into the etiology of flap failure by addressing the following question: Do differences in flap type result in clinically significant different vascular resistances and consequently anastomotic patency? A total of 15 human flaps were studied intraoperatively: 9 gracilis, 3 rectus abdominis, and 3 latissimus dorsi. The muscle was isolated on a single pedicle and hemodynamic stability was ensured. The venous pedicle was then divided. A timed collection of effluent was used to determine flow. Vascular resistance was calculated by dividing the change in pressure by the flow, and standardizing this for temperature and hematocrit. Average vascular resistance and standard deviation for the gracilis, rectus, and latissimus flaps was 10.34 +/- 7.77 mmHg per milliliter per minute, 2.79 +/- 1.50 mmHg per milliliter per minute, and 3.17 +/- 1.05 mmHg per milliliter per minute respectively. An inverse relationship between muscle vascular resistance and flap mass was found (p < 0.001). This indicates that larger muscles have less vascular resistance. The decreased resistance gives rise to higher flow rates and, as a result, potentially improved vein graft patency. The clinical implication is that a larger flap should be used when high flow-through is critical. The role of flap vascular territory makeup continues to be pursued.

Abdominal Muscles↗

A mucinous tumour of the urachus: adenoma or low grade mucinous cystic tumour of uncertain malignant potential?

We report a case of urachal glandular neoplasia in a male aged 72 years. The lesion had a papillary and villiform structure, and exhibited serrated features as seen in some colorectal neoplasms. The tumour cells expressed carcinoembryonic antigen, whereas the normal urachal epithelium did not. There was a striking resemblance to low grade mucinous cystic tumours of uncertain malignant potential as described in the appendix and elsewhere. Although such lesions in the urachus have been called adenomas, we argue that their potential to cause pseudomyxoma peritonei deserves a different terminology, and that 'mucinous tumour of uncertain malignant potential' is appropriate.

Adenoma↗

The pathology of acute appendicitis.

Although acute appendicitis is frequent, it is subject to common misconceptions. Furthermore, there is little good evidence to support some of our beliefs. This report reviews the role of the anatomic pathologist in diagnosis when acute appendicitis is suspected clinically and discusses what is known of its pathology. The conclusions that can be legitimately drawn from the literature are emphasized. A classification is proposed that incorporates intraluminal inflammation, acute mucosal inflammation, acute mucosal and submucosal inflammation, suppurative (phlegmonous) appendicitis, gangrenous appendicitis, and periappendicitis, and the significance of each of these diagnoses is discussed. The etiology and pathogenesis of acute appendicitis is reviewed. Contrary to popular belief, the best evidence indicates that obstruction is unlikely to be the primary cause, at least in the majority of cases. Ancillary techniques in the diagnosis of appendicitis, including laparoscopy and peritoneal aspiration cytology, are discussed.

Acute Disease↗

Mitotic and in situ end-labeling apoptotic indices as prognostic markers in malignant mesothelioma.

The prognostic role of mitotic and apoptotic indices in 60 patients with malignant mesothelioma was examined on hematoxylin-eosin-stained sections. The findings were compared with apoptotic indices determined by in situ end labeling (ISEL) in 35 of the cases. There was a significant survival advantage associated with lower mitotic counts and a lower apoptotic index defined by ISEL (P < .05). There was no association between the apoptotic index derived from the hematoxylin-eosin-stained sections and prognosis (P = .90). However, there was a positive association between the apoptotic counts calculated from hematoxylin-eosin- and ISEL-stained sections (P < .01). The mitotic count and ISEL apoptotic index are potentially useful markers of prognosis in malignant mesothelioma.

Aged↗

Acinar morphology in colorectal cancer is associated with survival but is not an independent prognostic variable.

AIMS: Microacinar morphology has been reported as a stage-independent prognostic variable for colorectal cancer. We have undertaken a retrospective analysis to test this observation in patients with colonic as well as rectal adenocarcinoma, and to assess interobserver agreement for identifying microacinar morphology. METHODS AND RESULTS: One hundred and eighty patients with colorectal cancer, 144 colonic and 36 rectal, were assigned to either macroacinar (144) or microacinar (36) groups. There was excellent correlation between two observers examining the colorectal cancers independently (kappa statistic, kappa = 0.87). Patients with microacinar tumours had a significantly reduced median survival compared with macroacinar lesions (46 and 87 months, respectively, P = 0.022) and this morphology was significantly associated with higher Dukes' stage (P = 0.007). Microacinar morphology lacked statistical significance when examined in a multivariate analysis with other prognostic variables, both when colonic and rectal tumours were examined either separately or as a combined colorectal group, but small numbers of rectal tumours in this study make it difficult to draw useful conclusions about microacinar morphology in rectal adenocarcinoma. CONCLUSIONS: Microacinar morphology was strongly associated with poor prognosis when examined in isolation but was not found to be an independent factor when examined with other prognostic variables.

Adenocarcinoma↗

M30 expression demonstrates apoptotic cells, correlates with in situ end-labeling, and is associated with Ki-67 expression in large intestinal neoplasms.

CONTEXT: The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 produced during apoptosis. It is reactive in formalin-fixed, paraffin-embedded tissue and has great potential in the study of apoptosis in clinical and experimental material. OBJECTIVES: To compare the results of M30 immunoexpression with a more established technique of demonstrating apoptosis in tissue sections, in situ end-labeling. A secondary objective was to compare the results with immunoexpression of the proliferation-associated antigen Ki-67. DESIGN: Retrospective analysis of adenomas and adenocarcinomas of the large intestine. INTERVENTIONS: Immunohistochemistry for M30 and Ki-67, and in situ end-labeling. Formalin-fixed, paraffin-embedded tissue was used. MAIN OUTCOME MEASURES: The number of cells positive for M30, Ki-67, and in situ end-labeling, expressed as a proportion of the total number of cells counted. RESULTS: A strong positive correlation was found between in situ end-labeling and expression of M30, although the counts were widely scattered around the regression line. Counts of Ki-67 were strongly correlated with both M30 expression and in situ end-labeling. Immunoexpression of M30 was generally easier to interpret than in situ end-labeling, and the procedures for M30 immunohistochemistry were technically less exacting. CONCLUSION: These findings support the application of M30 immunoreactivity in the study of apoptosis.

Adenocarcinoma↗

Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases.

Gastrointestinal stromal tumor or smooth muscle tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunohistochemically, and genetically differ from typical leiomyomas, leiomyosarcomas, and schwannomas. Because GISTs, like the interstitial cells of Cajal, the gastrointestinal pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the interstitial cells of Cajal has been recently proposed. Comparison of GISTs primary in the omentum and mesentery to GISTs primary in the tubular gastrointestinal tract is of particular diagnostic and histogenetic interest in view of the possible similarity of these tumors with the GIST group. In this study, we analyzed 14 omental and 12 mesenteric primary mesenchymal tumors representing smooth muscle tumors or GISTs. These tumors were phenotypically compared with gastric and small intestinal GISTs, leiomyomas of the esophagus, and leiomyosarcomas of the retroperitoneum. Most (13 of 14) omental and mesenteric (10 of 12) tumors showed histologic features similar to GISTs with elongated spindle cells or epithelioid cells with high cellularity; most of these tumors showed low mitotic activity. Omental and mesenteric GISTs were typically positive for CD117 and less consistently for CD34. They often showed alpha-smooth muscle actin reactivity but were virtually negative for desmin and S-100 protein. One omental and two mesenteric tumors showed features of leiomyosarcoma with ovoid, less elongated nuclei, cytoplasmic eosinophilia; all these tumors had significant mitotic activity. These tumors were positive for alpha-smooth muscle actin and two of them for desmin, but all were negative for CD34 and CD117, similar to retroperitoneal leiomyosarcomas. Tumor-related mortality occurred in the group of mesenteric GISTs, but not in the group of omental GISTs. In contrast, all three patients with a true leiomyosarcoma of the omentum or mesentery had documented liver metastases or died of tumor. In summary, we show that tumors phenotypically identical with GISTs occur as primary tumors in the omentum and mesentery. The occurrence of CD117-positive tumors outside the gastrointestinal tract militates against an origin of these tumors exclusively from the interstitial cells of Cajal.

Adult↗

Spindle cell squamous carcinoma of the esophagus: analysis of ploidy and tumor proliferative activity in a series of 13 cases.

Spindle cell squamous esophageal carcinomas are distinctive polypoid "biphasic" tumors in which the sarcoma-like phenotype usually predominates over the epithelial component. To biologically assess both phenotypes, we compared the tumoral proliferative activity and DNA ploidy between the two histological components of 13 polypoid spindle cell squamous carcinomas of the esophagus. We studied the tumoral proliferative index (TPI) using MIB 1 monoclonal antibody (Ki-67) and determined the DNA histogram by image cytometry on Feulgen-stained sections. The DNA histograms were classified into four types (I to IV) according to the degree of dispersion of the DNA. The TPI of the carcinomatous regions ranged from 0.20 to 0.63 (mean, 0.44) and from 0.55 to 0.85 for the sarcoma-like areas (mean, 0.68) P < .0001. In all cases, the sarcoma-like areas were aneuploid, and 37.5% of the carcinomatous regions were diploid. Also, in all instances the carcinomatous areas were of either histogram type I or II, and the sarcoma-like areas showed histograms of type II or III. We conclude that in esophageal spindle cell squamous carcinomas the sarcoma-like phenotype differs biologically in two ways from the carcinomatous: (1) it has a higher TPI and (2) it has higher aneuploidy with a greater dispersion of the DNA content. We postulate that these characteristics could give a "growth" advantage to the sarcoma-like component of these tumors and explain its predominance over the carcinomatous component.

Aged↗

Thorotrast associated nodular regenerative hyperplasia of the liver.

A case of nodular regenerative hyperplasia (NRH) of the liver is described in association with exposure to the radiographic contrast medium Thorotrast. This is the first case in which the pathological findings have been fully documented. It is suggested that NRH may have developed through Thorotrast induced damage to portal vein radicles.

Contrast Media↗